Aminu Kura | UPM - Universiti Putra Malaysia (original) (raw)

Papers by Aminu Kura

Public Health and Toxicology, Mar 31, 2024

Advances in pharmacology and pharmacy, Oct 1, 2023

INTRODUCTION 2. LITERATURE REVIEW Introductions Parkinson's disease Levodopa in the treatment of ... more INTRODUCTION 2. LITERATURE REVIEW Introductions Parkinson's disease Levodopa in the treatment of Parkinson's disease Blood brain barrier Nanomedicine Layered double hydroxide nanocomposite Synthesis and characterization of nanocomposite Characterization X-ray diffraction Transmission electron microscopy Fourier transform infrared spectroscopy Thermogravimetric analysis Ultraviolet-visible spectrophotometry Cellular uptake of nanocomposite Bio-distribution of nanocomposite Toxicity of nanocomposite Drug activity enhancement References 3. DEVELOPMENT OF A CONTROLLED-RELEASE ANTI

In Vitro Cellular & Developmental Biology – Animal, Sep 15, 2017

Polymer Composites, Feb 24, 2016

Chitosan nanoparticles (CSNPs) and perindopril erbumine (PE)-loaded chitosan nanoparticles (PE-CS... more Chitosan nanoparticles (CSNPs) and perindopril erbumine (PE)-loaded chitosan nanoparticles (PE-CSNPs) were prepared using the ionic gelation method with tripolyphosphate (TPP) as a crosslinking agent. The XRD pattern of the PE-CSNP nanocomposite shows suppression of the peaks corresponding to crystallized chitosan due to its conversion to the amorphous form after crosslinking and PE loading. The presence of the drug in the nanocomposite was confirmed by a shift in the FTIR transmittance peak from 1,289 to 1,279 cm−1. The mean diameter of the PE-CSNP nanocomposite was 44 nm. Analysis of the ultraviolet spectrum indicated that the loading efficiency and the encapsulation efficiency were 30.5% and 94.1%, respectively. The in vitro drug release profile was also determined by ultraviolet spectroscopy, which showed a sustained release over a period of 2 h (99.8%), starting with initial burst release (40% in 10 min). According to our results, no IC50 (the half maximal inhibitory concentration) against the 3T3 cell line was found for free PF or the PE-CSNP nanocomposite up to 100 μg mL−1.

The Scientific World Journal, 2014

We incorporated anti-Parkinsonian drug, levodopa (dopa), in Zn/Al-LDH by coprecipitation method t... more We incorporated anti-Parkinsonian drug, levodopa (dopa), in Zn/Al-LDH by coprecipitation method to form dopa-LDH nanocomposite. Further coating of Tween-80 on the external surfaces of dopa-LDH nanocomposite was achieved through the oxygen of C=O group of Tween-80 with the layer of dopa-LDH nanocomposite. The final product is called Tween-dopa-LDH nanocomposite. The X-ray diffraction indicates that the Tween-dopa-LDH nanocomposite was formed by aggregation structure. From the TGA data, the Tween-80 loading on the surface of LDH and dopa-LDH was 8.6 and 7.4%, respectively. The effect of coating process on the dopa release from Tween-dopa-LDH nanocomposite was also studied. The release from Tween-dopa-LDH nanocomposite shows slower release compared to the release of the drug from dopa-LDH nanocomposite as done previously in our study, presumably due to the retarding shielding effect. The cell viability study using PC12 showed improved viability with Tween-80 coating on dopa-LDH nanocomposite as studied by mitochondrial dehydrogenase activity (MTT assay).

BioMed Research International, 2014

Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of antifungal activity. ... more Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of antifungal activity. In the present study, we prepared a nystatin nanocomposite (Nyst-CS-MNP) by loading nystatin (Nyst) on chitosan (CS) coated magnetic nanoparticles (MNPs). The magnetic nanocomposites were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), vibrating sample magnetometer (VSM), and scanning electron microscopy (SEM). The XRD results showed that the MNPs and nanocomposite are pure magnetite. The FTIR analysis confirmed the binding of CS on the surface of the MNPs and also the loading of Nyst in the nanocomposite. The Nyst drug loading was estimated using UV-Vis instrumentation and showing a 14.9% loading in the nanocomposite. The TEM size image of the MNPs, CS-MNP, and Nyst-CS-MNP was 13, 11, and 8 nm, respectively. The release profile of the Nyst drug from the nanocomposite followed a pseudo-second-order kinetic model. The antimicrobial activity of the as-synthesized Nyst and Nyst-CS-MNP nanocomposite was evaluated using an agar diffusion method and showed enhanced antifungal activity against Candida albicans. In this manner, this study introduces a novel nanocomposite that can decrease fungus activity on-demand for numerous medical applications.

Drug Design Development and Therapy, Sep 1, 2013

Background: Iron oxide nanoparticles are of considerable interest because of their use in magneti... more Background: Iron oxide nanoparticles are of considerable interest because of their use in magnetic recording tape, ferrofluid, magnetic resonance imaging, drug delivery, and treatment of cancer. The specific morphology of nanoparticles confers an ability to load, carry, and release different types of drugs. Methods and results: We synthesized superparamagnetic nanoparticles containing pure iron oxide with a cubic inverse spinal structure. Fourier transform infrared spectra confirmed that these Fe 3 O 4 nanoparticles could be successfully coated with active drug, and thermogravimetric and differential thermogravimetric analyses showed that the thermal stability of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe 3 O 4 nanoparticles and the FCMP nanocomposite were generally spherical, with an average diameter of 9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP nanocomposite was found to be sustained and governed by pseudo-second order kinetics. In order to improve drug loading and release behavior, we prepared a novel nanocomposite (FCMP-D), ie, Fe 3 O 4 nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but using a different solvent for the drug. The results for FCMP-D did not demonstrate "burst release" and the maximum percentage release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and 55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH 7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line. Conclusion: Iron oxide coated with chitosan containing 6-mercaptopurine prepared using a coprecipitation method has the potential to be used as a controlled-release formulation. These nanoparticles may serve as an alternative drug delivery system for the treatment of cancer, with the added advantage of sparing healthy surrounding cells and tissue.

Applied Nanoscience, Mar 30, 2018

A theranostic nanocomposite was developed using anticancer agent, protocatechuic acid (PA) and ma... more A theranostic nanocomposite was developed using anticancer agent, protocatechuic acid (PA) and magnetic resonance imaging (MRI) contrast agent gadolinium nitrate (Gd) for simultaneous delivery using layered double hydroxide (LDH) as the delivery agent. Gold nanoparticles (AuNPs) were adsorbed on the surface of the LDH, which served as a complementary contrast agent. Based on the concept of supramolecular chemistry (SPC) and multimodal delivery system (MDS), the PA and Gd guests were first intercalated into the LDH host and subsequently AuNPs were surface adsorbed as the third guest. The nanohybrid developed was named MAPGAu. The MAPGAu was exposed to various characterizations at different stages of synthesis, starting with XRD analysis, which was used to confirm the intercalation episode and surface adsorption of the guest molecules. Consequently, FESEM, Hi-TEM, XRD, ICP-OES, CHNS, FTIR and UV-Vis analyses were done on the nanohybrids. The result of XRD analysis indicated successful intercalation of the Gd and PA as well the adsorption of AuNPs. The UV-Vis release study showed 90% of the intercalated drug was released at pH 4.8, which is the pH of the cancer cells. The FESEM and TEM micrographs obtained equally confirmed the formation of MAGPAu nanocomposite, with AuNPs conspicuously deposited on the LDH surface. The cytotoxicity study of the nanohybrid also showed insignificant toxicity to normal cell lines and significant toxicity to cancer cell lines. The developed MAGPAu nanocomposite has shown prospects for future theranostic cancer treatment.

Materials Chemistry and Physics, 2020

A theranostic nanodelivery system for simultaneous therapeutics and magnetic resonance imaging (M... more A theranostic nanodelivery system for simultaneous therapeutics and magnetic resonance imaging (MRI) diagnostic agents' delivery was successful synthesized, using Zn/Al layered double hydroxide (LDH) as the nanocarrier, chlorogenic acid (CA) as the therapeutic agent and gadolinium as the diagnostic contrast agent. The contrast of the MR image was improved with gold nanoparticles (AuNPs), which were coated on the surface of the nanohybrid (ZAGCAu). The kinetic release study was conducted with UV-Vis spectrophotometer and high release was observed (up to 90%). Other characterizations conducted on the nanohybrid include; HRTEM, XRD, FTIR, FESEM and Elemental analysis, which all confirmed the theranostic nanohybrid development (ZAGCAu). Cell viability test (in vitro) was also carried out with ZAGCAu on normal cell lines (3T3) and liver cancer cell lines (HepG2). The results indicated relative cytotoxicity against HepG2 and slight toxicity on the 3T3. The preliminary MRI contrast property of the ZAGCAu was tested to ascertain the inherent signal optimization on a 3 T MRI machine. Various concentrations of the ZAGCAu indicated enhanced T1 and T2 signals in comparison with the Gd and water references used. The preliminary studies conducted on the ZAGCAu nanohybrid developed in this work shows its potentiality as a future theranostic agent for simultaneous diagnostic and therapeutic functions in cancer treatment.

International Journal of Nanomedicine, Mar 1, 2013

A new layered organic-inorganic nanocomposite material with an anti-parkinsonian active compound,... more A new layered organic-inorganic nanocomposite material with an anti-parkinsonian active compound, L-3-(3,4-dihydroxyphenyl) alanine (levodopa), intercalated into the inorganic interlayers of a Zn/Al-layered double hydroxide (LDH) was synthesized using a direct coprecipitation method. The resulting nanocomposite was composed of the organic moiety, levodopa, sandwiched between Zn/Al-LDH inorganic interlayers. The basal spacing of the resulting nanocomposite was 10.9 Å. The estimated loading of levodopa in the nanocomposite was approximately 16% (w/w). A Fourier transform infrared study showed that the absorption bands of the nanocomposite were characteristic of both levodopa and Zn/Al-LDH, which further confirmed intercalation, and that the intercalated organic moiety in the nanocomposite was more thermally stable than free levodopa. The resulting nanocomposite showed sustained-release properties, so can be used in a controlled-release formulation. Cytotoxicity analysis using an MTT assay also showed increased cell viability of 3T3 cells exposed to the newly synthesized nanocomposite compared with those exposed to pure levodopa after 72 hours of exposure.

International Journal of Nanomedicine, Jul 1, 2016

This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a s... more This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as "flavonosome". Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA-phosphatidylcholine) through four different methods of synthesis-bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug-carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA-phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of-39.07±3.55 mV, and the entrapment efficiency was .98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert .85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate.

Journal of Materials Science, Sep 9, 2014

Iron oxide nanoparticles (FNPs) were synthesized due to low toxicity and their ability to immobil... more Iron oxide nanoparticles (FNPs) were synthesized due to low toxicity and their ability to immobilize biological materials on their surfaces by the coprecipitation of iron salts in ammonia hydroxide followed by coating it with polyethylene glycol (PEG) to minimize the aggregation of iron oxide nanoparticles and enhance the effect of nanoparticles for biological applications. Then, the FNPs-PEG was loaded with perindopril erbumine (PE), an antihypertensive compound to form a new nanocomposite (FPEGPE). Transmission electron microscopy results showed that there are no significant differences between the sizes of FNPs and FPEGPE nanocomposite. The existence of PEG-PE was supported by the FTIR and TGA analyses. The PE loading (10.3 %) and the release profiles from FPEGPE nanocomposite were estimated using ultraviolet-visible spectroscopy which showed that up to 60.8 and 83.1 % of the adsorbed drug was released in 4223 and 1231 min at pH 7.4 and 4.8, respectively. However, the release of PE was completed very fast from a physical mixture (FNPs-PEG-PE) after 5 and 7 min at pH 4.8 and 7.4, respectively, which reveals that the release of PE from the physical mixture is not in the sustained-release manner. Cytotoxicity study showed that free PE presented slightly higher toxicity than the FNPs and FPEGPE nanocomposite. Therefore, the decrease toxicity against mouse normal fibroblast (3T3) cell lines prospective of this nanocomposite together with controlled-release behavior provided evidence of the possible beneficial biological activities of this new nanocomposite for nanopharmaceutical applications for both oral and non-oral routes.

The Scientific World Journal, 2014

The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles... more The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe 3 O 4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR) revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-secondorder kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG.

International Journal of Nanomedicine, Feb 1, 2016

A local antibiotic delivery system (LADS) with biodegradable drug vehicles is recognized as the m... more A local antibiotic delivery system (LADS) with biodegradable drug vehicles is recognized as the most effective therapeutic approach for the treatment of osteomyelitis. However, the design of a biodegradable LADS with high therapeutic efficacy is too costly and demanding. In this research, a low-cost, facile method was used to design vancomycin-loaded aragonite nanoparticles (VANPs) with the aim of understanding its potency in developing a nanoantibiotic bone implant for the treatment of osteomyelitis. The aragonite nanoparticles (ANPs) were synthesized from cockle shells by a hydrothermal approach using a zwitterionic surfactant. VANPs were prepared using antibiotic ratios of several nanoparticles, and the formulation (1:4) with the highest drug-loading efficiency (54.05%) was used for physicochemical, in vitro drug release, and biological evaluation. Physiochemical characterization of VANP was performed by using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, and Zetasizer. No significant differences were observed between VANP and ANP in terms of size and morphology as both samples were cubic shaped with sizes of approximately 35 nm. The Fourier transform infrared spectroscopy of VANP indicated a weak noncovalent interaction between ANP and vancomycin, while the zeta potential values were slightly increased from −19.4±3.3 to −21.2±5.7 mV after vancomycin loading. VANP displayed 120 hours (5 days) release profile of vancomycin that exhibited high antibacterial effect against methicillin-resistant Staphylococcus aureus ATCC 29213. The cell proliferation assay showed 80% cell viability of human fetal osteoblast cell line 1.19 treated with the highest concentration of VANP (250 µg/mL), indicating good biocompatibility of VANP. In summary, VANP is a potential formulation for the development of an LADS against osteomyelitis with optimal antibacterial efficacy, good bone resorbability, and biocompatibility.

Beni-Suef University Journal of Basic and Applied Sciences, Jul 29, 2022

Background: Natural products are utilized globally for the management of diseases such as diabete... more Background: Natural products are utilized globally for the management of diseases such as diabetes mellitus. Carrot seeds are ethnobotanically used in the management of diabetes mellitus. This study investigated the in vitro and in vivo antihyperglycemic activities of verbenone and L-arginine, which are compounds found in carrot seed. Results: Verbenone, L-arginine, and their ratios combination expressed significantly in vitro α-amylase inhibitory activity with IC 50 of 13.00, 12.69, and 13.30 µg/mL respectively compared with acarbose (IC 50 = 12.64 µg/mL) and significant in vitro α-glucosidases inhibitory activity with IC 50 of 29.01, 23.76 and 30.11 µg/mL respectively compared with acarbose (IC 50 = 16.80 µg/mL). Furthermore, the compounds improved glucose uptake in yeast cells and inhibited haemoglobin glycation in vitro. In the in vivo study, the compounds significantly reduced the levels of blood glucose, the levels of liver total cholesterol, and liver triacylglycerol, the calculated cardiovascular indices, whereas the level of plasma high density lipoprotein (HDL) cholesterol was significantly elevated in all diabetic treated mice. Conclusion: The data revealed the in vitro antidiabetic activity of verbenone and L-arginine. Also, the compounds ameliorated hyperglycemia, hyperlipidemia and other diabetic-induced biochemical alterations in NAD-STZ-induced diabetic mice model. Highlights • Verbenone, a natural bicyclic ketone monoterpene, and L-arginine, a natural amino acid, areboth found in Daucus carota and other medicinal plants useful in the management of diabetesmellitus. • Verbenone and L-arginine possess in vitro antidiabetic activities, improve glucose uptake, andinhibited haemoglobin glycation. • Verbenone possesses in vivo antidiabetic activities in NAD-STZ-induced diabetic mice withpotential synergetic effect with L-arginine. • Verbenone and L-arginine possess antihyperlipidemic properties and could prevent the risk ofcardiovascular diseases in NAD-STZ-treated mice.

Nanoscale Research Letters, Mar 1, 2015

Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug b... more Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study (P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

Chemistry Central Journal, Aug 10, 2014

The production of layered double hydroxide(LDH) nanocomposite as an alternative drug delivery sys... more The production of layered double hydroxide(LDH) nanocomposite as an alternative drug delivery system against various ailments is on the increase. Their toxicity potential is usually dose and time dependent with particle sizes, shapes and surface charge playing some role both in the in vitro and in vivo studies. The reticular endothelial system of especially the liver and spleen were shown to sequestrate most of these nanocomposite, especially those with sizes greater than 50 nm. The intracellular drug delivery by these particles is mainly via endocytotic pathways aided by the surface charges in most cases. However, structural modification of these nanocomposite via coating using different types of material may lower the toxicity where present. More importantly, the coating may serve as targeting ligand hence, directing drug distribution and leading to proper drug delivery to specific area of need; it equally decreases the unwanted nanocomposite accumulation in especially the liver and spleen. These nanocomposite have the advantage of wider bio-distribution irrespective of route of administration, excellent targeted delivery potential with ease of synthetic modification including coating.

Nanoscale Research Letters, May 24, 2014

Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for de... more Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Cooperation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/ kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.

Public Health and Toxicology, Mar 31, 2024

Advances in pharmacology and pharmacy, Oct 1, 2023

INTRODUCTION 2. LITERATURE REVIEW Introductions Parkinson's disease Levodopa in the treatment of ... more INTRODUCTION 2. LITERATURE REVIEW Introductions Parkinson's disease Levodopa in the treatment of Parkinson's disease Blood brain barrier Nanomedicine Layered double hydroxide nanocomposite Synthesis and characterization of nanocomposite Characterization X-ray diffraction Transmission electron microscopy Fourier transform infrared spectroscopy Thermogravimetric analysis Ultraviolet-visible spectrophotometry Cellular uptake of nanocomposite Bio-distribution of nanocomposite Toxicity of nanocomposite Drug activity enhancement References 3. DEVELOPMENT OF A CONTROLLED-RELEASE ANTI

In Vitro Cellular & Developmental Biology – Animal, Sep 15, 2017

Polymer Composites, Feb 24, 2016

Chitosan nanoparticles (CSNPs) and perindopril erbumine (PE)-loaded chitosan nanoparticles (PE-CS... more Chitosan nanoparticles (CSNPs) and perindopril erbumine (PE)-loaded chitosan nanoparticles (PE-CSNPs) were prepared using the ionic gelation method with tripolyphosphate (TPP) as a crosslinking agent. The XRD pattern of the PE-CSNP nanocomposite shows suppression of the peaks corresponding to crystallized chitosan due to its conversion to the amorphous form after crosslinking and PE loading. The presence of the drug in the nanocomposite was confirmed by a shift in the FTIR transmittance peak from 1,289 to 1,279 cm−1. The mean diameter of the PE-CSNP nanocomposite was 44 nm. Analysis of the ultraviolet spectrum indicated that the loading efficiency and the encapsulation efficiency were 30.5% and 94.1%, respectively. The in vitro drug release profile was also determined by ultraviolet spectroscopy, which showed a sustained release over a period of 2 h (99.8%), starting with initial burst release (40% in 10 min). According to our results, no IC50 (the half maximal inhibitory concentration) against the 3T3 cell line was found for free PF or the PE-CSNP nanocomposite up to 100 μg mL−1.

The Scientific World Journal, 2014

We incorporated anti-Parkinsonian drug, levodopa (dopa), in Zn/Al-LDH by coprecipitation method t... more We incorporated anti-Parkinsonian drug, levodopa (dopa), in Zn/Al-LDH by coprecipitation method to form dopa-LDH nanocomposite. Further coating of Tween-80 on the external surfaces of dopa-LDH nanocomposite was achieved through the oxygen of C=O group of Tween-80 with the layer of dopa-LDH nanocomposite. The final product is called Tween-dopa-LDH nanocomposite. The X-ray diffraction indicates that the Tween-dopa-LDH nanocomposite was formed by aggregation structure. From the TGA data, the Tween-80 loading on the surface of LDH and dopa-LDH was 8.6 and 7.4%, respectively. The effect of coating process on the dopa release from Tween-dopa-LDH nanocomposite was also studied. The release from Tween-dopa-LDH nanocomposite shows slower release compared to the release of the drug from dopa-LDH nanocomposite as done previously in our study, presumably due to the retarding shielding effect. The cell viability study using PC12 showed improved viability with Tween-80 coating on dopa-LDH nanocomposite as studied by mitochondrial dehydrogenase activity (MTT assay).

BioMed Research International, 2014

Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of antifungal activity. ... more Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of antifungal activity. In the present study, we prepared a nystatin nanocomposite (Nyst-CS-MNP) by loading nystatin (Nyst) on chitosan (CS) coated magnetic nanoparticles (MNPs). The magnetic nanocomposites were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), vibrating sample magnetometer (VSM), and scanning electron microscopy (SEM). The XRD results showed that the MNPs and nanocomposite are pure magnetite. The FTIR analysis confirmed the binding of CS on the surface of the MNPs and also the loading of Nyst in the nanocomposite. The Nyst drug loading was estimated using UV-Vis instrumentation and showing a 14.9% loading in the nanocomposite. The TEM size image of the MNPs, CS-MNP, and Nyst-CS-MNP was 13, 11, and 8 nm, respectively. The release profile of the Nyst drug from the nanocomposite followed a pseudo-second-order kinetic model. The antimicrobial activity of the as-synthesized Nyst and Nyst-CS-MNP nanocomposite was evaluated using an agar diffusion method and showed enhanced antifungal activity against Candida albicans. In this manner, this study introduces a novel nanocomposite that can decrease fungus activity on-demand for numerous medical applications.

Drug Design Development and Therapy, Sep 1, 2013

Background: Iron oxide nanoparticles are of considerable interest because of their use in magneti... more Background: Iron oxide nanoparticles are of considerable interest because of their use in magnetic recording tape, ferrofluid, magnetic resonance imaging, drug delivery, and treatment of cancer. The specific morphology of nanoparticles confers an ability to load, carry, and release different types of drugs. Methods and results: We synthesized superparamagnetic nanoparticles containing pure iron oxide with a cubic inverse spinal structure. Fourier transform infrared spectra confirmed that these Fe 3 O 4 nanoparticles could be successfully coated with active drug, and thermogravimetric and differential thermogravimetric analyses showed that the thermal stability of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe 3 O 4 nanoparticles and the FCMP nanocomposite were generally spherical, with an average diameter of 9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP nanocomposite was found to be sustained and governed by pseudo-second order kinetics. In order to improve drug loading and release behavior, we prepared a novel nanocomposite (FCMP-D), ie, Fe 3 O 4 nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but using a different solvent for the drug. The results for FCMP-D did not demonstrate "burst release" and the maximum percentage release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and 55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH 7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line. Conclusion: Iron oxide coated with chitosan containing 6-mercaptopurine prepared using a coprecipitation method has the potential to be used as a controlled-release formulation. These nanoparticles may serve as an alternative drug delivery system for the treatment of cancer, with the added advantage of sparing healthy surrounding cells and tissue.

Applied Nanoscience, Mar 30, 2018

A theranostic nanocomposite was developed using anticancer agent, protocatechuic acid (PA) and ma... more A theranostic nanocomposite was developed using anticancer agent, protocatechuic acid (PA) and magnetic resonance imaging (MRI) contrast agent gadolinium nitrate (Gd) for simultaneous delivery using layered double hydroxide (LDH) as the delivery agent. Gold nanoparticles (AuNPs) were adsorbed on the surface of the LDH, which served as a complementary contrast agent. Based on the concept of supramolecular chemistry (SPC) and multimodal delivery system (MDS), the PA and Gd guests were first intercalated into the LDH host and subsequently AuNPs were surface adsorbed as the third guest. The nanohybrid developed was named MAPGAu. The MAPGAu was exposed to various characterizations at different stages of synthesis, starting with XRD analysis, which was used to confirm the intercalation episode and surface adsorption of the guest molecules. Consequently, FESEM, Hi-TEM, XRD, ICP-OES, CHNS, FTIR and UV-Vis analyses were done on the nanohybrids. The result of XRD analysis indicated successful intercalation of the Gd and PA as well the adsorption of AuNPs. The UV-Vis release study showed 90% of the intercalated drug was released at pH 4.8, which is the pH of the cancer cells. The FESEM and TEM micrographs obtained equally confirmed the formation of MAGPAu nanocomposite, with AuNPs conspicuously deposited on the LDH surface. The cytotoxicity study of the nanohybrid also showed insignificant toxicity to normal cell lines and significant toxicity to cancer cell lines. The developed MAGPAu nanocomposite has shown prospects for future theranostic cancer treatment.

Materials Chemistry and Physics, 2020

A theranostic nanodelivery system for simultaneous therapeutics and magnetic resonance imaging (M... more A theranostic nanodelivery system for simultaneous therapeutics and magnetic resonance imaging (MRI) diagnostic agents' delivery was successful synthesized, using Zn/Al layered double hydroxide (LDH) as the nanocarrier, chlorogenic acid (CA) as the therapeutic agent and gadolinium as the diagnostic contrast agent. The contrast of the MR image was improved with gold nanoparticles (AuNPs), which were coated on the surface of the nanohybrid (ZAGCAu). The kinetic release study was conducted with UV-Vis spectrophotometer and high release was observed (up to 90%). Other characterizations conducted on the nanohybrid include; HRTEM, XRD, FTIR, FESEM and Elemental analysis, which all confirmed the theranostic nanohybrid development (ZAGCAu). Cell viability test (in vitro) was also carried out with ZAGCAu on normal cell lines (3T3) and liver cancer cell lines (HepG2). The results indicated relative cytotoxicity against HepG2 and slight toxicity on the 3T3. The preliminary MRI contrast property of the ZAGCAu was tested to ascertain the inherent signal optimization on a 3 T MRI machine. Various concentrations of the ZAGCAu indicated enhanced T1 and T2 signals in comparison with the Gd and water references used. The preliminary studies conducted on the ZAGCAu nanohybrid developed in this work shows its potentiality as a future theranostic agent for simultaneous diagnostic and therapeutic functions in cancer treatment.

International Journal of Nanomedicine, Mar 1, 2013

A new layered organic-inorganic nanocomposite material with an anti-parkinsonian active compound,... more A new layered organic-inorganic nanocomposite material with an anti-parkinsonian active compound, L-3-(3,4-dihydroxyphenyl) alanine (levodopa), intercalated into the inorganic interlayers of a Zn/Al-layered double hydroxide (LDH) was synthesized using a direct coprecipitation method. The resulting nanocomposite was composed of the organic moiety, levodopa, sandwiched between Zn/Al-LDH inorganic interlayers. The basal spacing of the resulting nanocomposite was 10.9 Å. The estimated loading of levodopa in the nanocomposite was approximately 16% (w/w). A Fourier transform infrared study showed that the absorption bands of the nanocomposite were characteristic of both levodopa and Zn/Al-LDH, which further confirmed intercalation, and that the intercalated organic moiety in the nanocomposite was more thermally stable than free levodopa. The resulting nanocomposite showed sustained-release properties, so can be used in a controlled-release formulation. Cytotoxicity analysis using an MTT assay also showed increased cell viability of 3T3 cells exposed to the newly synthesized nanocomposite compared with those exposed to pure levodopa after 72 hours of exposure.

International Journal of Nanomedicine, Jul 1, 2016

This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a s... more This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as "flavonosome". Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA-phosphatidylcholine) through four different methods of synthesis-bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug-carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA-phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of-39.07±3.55 mV, and the entrapment efficiency was .98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert .85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate.

Journal of Materials Science, Sep 9, 2014

Iron oxide nanoparticles (FNPs) were synthesized due to low toxicity and their ability to immobil... more Iron oxide nanoparticles (FNPs) were synthesized due to low toxicity and their ability to immobilize biological materials on their surfaces by the coprecipitation of iron salts in ammonia hydroxide followed by coating it with polyethylene glycol (PEG) to minimize the aggregation of iron oxide nanoparticles and enhance the effect of nanoparticles for biological applications. Then, the FNPs-PEG was loaded with perindopril erbumine (PE), an antihypertensive compound to form a new nanocomposite (FPEGPE). Transmission electron microscopy results showed that there are no significant differences between the sizes of FNPs and FPEGPE nanocomposite. The existence of PEG-PE was supported by the FTIR and TGA analyses. The PE loading (10.3 %) and the release profiles from FPEGPE nanocomposite were estimated using ultraviolet-visible spectroscopy which showed that up to 60.8 and 83.1 % of the adsorbed drug was released in 4223 and 1231 min at pH 7.4 and 4.8, respectively. However, the release of PE was completed very fast from a physical mixture (FNPs-PEG-PE) after 5 and 7 min at pH 4.8 and 7.4, respectively, which reveals that the release of PE from the physical mixture is not in the sustained-release manner. Cytotoxicity study showed that free PE presented slightly higher toxicity than the FNPs and FPEGPE nanocomposite. Therefore, the decrease toxicity against mouse normal fibroblast (3T3) cell lines prospective of this nanocomposite together with controlled-release behavior provided evidence of the possible beneficial biological activities of this new nanocomposite for nanopharmaceutical applications for both oral and non-oral routes.

The Scientific World Journal, 2014

The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles... more The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe 3 O 4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR) revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-secondorder kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG.

International Journal of Nanomedicine, Feb 1, 2016

A local antibiotic delivery system (LADS) with biodegradable drug vehicles is recognized as the m... more A local antibiotic delivery system (LADS) with biodegradable drug vehicles is recognized as the most effective therapeutic approach for the treatment of osteomyelitis. However, the design of a biodegradable LADS with high therapeutic efficacy is too costly and demanding. In this research, a low-cost, facile method was used to design vancomycin-loaded aragonite nanoparticles (VANPs) with the aim of understanding its potency in developing a nanoantibiotic bone implant for the treatment of osteomyelitis. The aragonite nanoparticles (ANPs) were synthesized from cockle shells by a hydrothermal approach using a zwitterionic surfactant. VANPs were prepared using antibiotic ratios of several nanoparticles, and the formulation (1:4) with the highest drug-loading efficiency (54.05%) was used for physicochemical, in vitro drug release, and biological evaluation. Physiochemical characterization of VANP was performed by using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, and Zetasizer. No significant differences were observed between VANP and ANP in terms of size and morphology as both samples were cubic shaped with sizes of approximately 35 nm. The Fourier transform infrared spectroscopy of VANP indicated a weak noncovalent interaction between ANP and vancomycin, while the zeta potential values were slightly increased from −19.4±3.3 to −21.2±5.7 mV after vancomycin loading. VANP displayed 120 hours (5 days) release profile of vancomycin that exhibited high antibacterial effect against methicillin-resistant Staphylococcus aureus ATCC 29213. The cell proliferation assay showed 80% cell viability of human fetal osteoblast cell line 1.19 treated with the highest concentration of VANP (250 µg/mL), indicating good biocompatibility of VANP. In summary, VANP is a potential formulation for the development of an LADS against osteomyelitis with optimal antibacterial efficacy, good bone resorbability, and biocompatibility.

Beni-Suef University Journal of Basic and Applied Sciences, Jul 29, 2022

Background: Natural products are utilized globally for the management of diseases such as diabete... more Background: Natural products are utilized globally for the management of diseases such as diabetes mellitus. Carrot seeds are ethnobotanically used in the management of diabetes mellitus. This study investigated the in vitro and in vivo antihyperglycemic activities of verbenone and L-arginine, which are compounds found in carrot seed. Results: Verbenone, L-arginine, and their ratios combination expressed significantly in vitro α-amylase inhibitory activity with IC 50 of 13.00, 12.69, and 13.30 µg/mL respectively compared with acarbose (IC 50 = 12.64 µg/mL) and significant in vitro α-glucosidases inhibitory activity with IC 50 of 29.01, 23.76 and 30.11 µg/mL respectively compared with acarbose (IC 50 = 16.80 µg/mL). Furthermore, the compounds improved glucose uptake in yeast cells and inhibited haemoglobin glycation in vitro. In the in vivo study, the compounds significantly reduced the levels of blood glucose, the levels of liver total cholesterol, and liver triacylglycerol, the calculated cardiovascular indices, whereas the level of plasma high density lipoprotein (HDL) cholesterol was significantly elevated in all diabetic treated mice. Conclusion: The data revealed the in vitro antidiabetic activity of verbenone and L-arginine. Also, the compounds ameliorated hyperglycemia, hyperlipidemia and other diabetic-induced biochemical alterations in NAD-STZ-induced diabetic mice model. Highlights • Verbenone, a natural bicyclic ketone monoterpene, and L-arginine, a natural amino acid, areboth found in Daucus carota and other medicinal plants useful in the management of diabetesmellitus. • Verbenone and L-arginine possess in vitro antidiabetic activities, improve glucose uptake, andinhibited haemoglobin glycation. • Verbenone possesses in vivo antidiabetic activities in NAD-STZ-induced diabetic mice withpotential synergetic effect with L-arginine. • Verbenone and L-arginine possess antihyperlipidemic properties and could prevent the risk ofcardiovascular diseases in NAD-STZ-treated mice.

Nanoscale Research Letters, Mar 1, 2015

Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug b... more Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study (P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

Chemistry Central Journal, Aug 10, 2014

The production of layered double hydroxide(LDH) nanocomposite as an alternative drug delivery sys... more The production of layered double hydroxide(LDH) nanocomposite as an alternative drug delivery system against various ailments is on the increase. Their toxicity potential is usually dose and time dependent with particle sizes, shapes and surface charge playing some role both in the in vitro and in vivo studies. The reticular endothelial system of especially the liver and spleen were shown to sequestrate most of these nanocomposite, especially those with sizes greater than 50 nm. The intracellular drug delivery by these particles is mainly via endocytotic pathways aided by the surface charges in most cases. However, structural modification of these nanocomposite via coating using different types of material may lower the toxicity where present. More importantly, the coating may serve as targeting ligand hence, directing drug distribution and leading to proper drug delivery to specific area of need; it equally decreases the unwanted nanocomposite accumulation in especially the liver and spleen. These nanocomposite have the advantage of wider bio-distribution irrespective of route of administration, excellent targeted delivery potential with ease of synthetic modification including coating.

Nanoscale Research Letters, May 24, 2014

Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for de... more Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Cooperation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/ kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.