Noha Nafee | Kuwait University (original) (raw)
Papers by Noha Nafee
Polymer-conjugate drug/protein Carbon nanotubes Nanocarriers for cancer therapy & detection Dendr... more Polymer-conjugate drug/protein Carbon nanotubes Nanocarriers for cancer therapy & detection Dendrimers Dendrimers Liposomes Liposomes Surface modified nanoparticles Surface modified nanoparticles Polymeric micelles Polymeric micelles Polymer-conjugate drug/protein Polymer-conjugate drug/protein Carbon nanotubes Carbon nanotubes Chapter 5 Cytotoxicity of chitosan-modified PLGA nanoparticles Relevance of the colloidal stability on the toxicity results* *This chapter has been submitted for publication as a journal article: N. Nafee, M. Schneider, U.F. Schäfer, and C.-M. Lehr. Relevance of the colloidal stability of chitosan-modified PLGA nanoparticles on their cytotoxicity profile. International Journal of Pharmaceutics. (submitted article) Chapter 5: Cytotoxicity of chitosan-modified PLGA nanoparticles
SUMMARY The hydrophobic nature of aluminium phthalocyanine causes its aggregation in biological f... more SUMMARY The hydrophobic nature of aluminium phthalocyanine causes its aggregation in biological fluids, thus abolishes its photoactivity and limits its biological application. Amphiphilic biodegradable block copolymers were synthesized and allowed to assemble in aqueous solution into nanoparticles (<100 nm). AlPc encapsulated in these polymeric nanoparticles exhibit better photodynamic activity, lower dark toxicity and prolonged release behavior compared to the free photosensitizer. Amphiphilic nanoparticles could be considered a promising carrier for hydrophobic photosensitizers.
SUMMARY Plain solid lipid nanoparticles (SLNs) were formulated by melt emulsification method usin... more SUMMARY Plain solid lipid nanoparticles (SLNs) were formulated by melt emulsification method using different lipids, fatty acids and waxes stabilized by polymeric emulsifying agents. The optimized nanoparticles were spherical in the size range of 100-200 nm with narrow size distribution as confirmed by polydispersity index (PDI < 0.2). SLNs were negatively charged with ζ-potential values between -3 and -18 mV. Amphiphilic lipids provided smaller and more stable SLNs compared to fatty acids and waxes. For the pulmonary delivery purposes, SLNs were nebulized using jet nebulizers. Results showed promising aerosol output rate as well as colloidal stability. INTRODUCTION Currently, lipid-based nanocarriers including SLNs and Nano-structured lipid carriers (NLCs) become an appealing advance in versatile pharmaceutical applications [1]. SLNs consist of nanosized solid lipid particles dispersed in aqueous medium. SLNs have the advantages of acquisition of biocompatible and biodegradable ...
European Journal of Pharmaceutics and Biopharmaceutics, 2018
Mucus-penetrating solid lipid nanoparticles for the treatment of cystic fibrosis: Proof of concep... more Mucus-penetrating solid lipid nanoparticles for the treatment of cystic fibrosis: Proof of concept, challenges and pitfalls,
Colloids and surfaces. B, Biointerfaces, Jan 10, 2015
A series of cyclodextrin-based star polymers were synthesized using β-cyclodextrin (CD) as hydrop... more A series of cyclodextrin-based star polymers were synthesized using β-cyclodextrin (CD) as hydrophilic core, methyl methacrylate (MMA) and tert-butyl acrylate (tBA) as hydrophobic arms. Star polymers, either homopolymers or random/block copolymers, showed narrow molecular weight distributions. Grafting hydrophobic arms created CD-based nanoparticles (CD-NPs) in the size range (130-200nm) with narrow PdI <0.15 and slightly negative ζ-potential. Particle surface could be modified with chitosan to impart a positive surface charge. Colloidal stability of CD-NPs was a function of pH as revealed by the pH-titration curves. CD-NPs were used as carrier for the chemotherapeutic drug idarubicin (encapsulation efficiency, EE ∼40%) ensuring prolonged release profile (∼80% after 48h). For cell-based studies, coumarin-6 was encapsulated as a fluorescent marker (EE ∼75%). Uptake studies carried out on A549 and Caco-2 cell lines proved the uptake of coumarin-loaded NPs as a function of time and ...
European Journal of Pharmaceutics and Biopharmaceutics, 2012
International Journal of Pharmaceutics, 2011
Nanoparticles delivery of oligonucleotides represents a potential approach for cancer treatment. ... more Nanoparticles delivery of oligonucleotides represents a potential approach for cancer treatment. However, most of the experiments were based on established cancer cell lines and may not reflect the original solid tumor in vivo. Both, tumor microenvironment and tumor cell biological properties in the tumor can influence the delivery efficiency of oligonucleotides. Therefore, it is important to understand the effect of nanoparticles delivery of oligonucleotides on tumor response in intact tissue architecture of individual tumors. We used freshly isolated human tumor tissue slices and primary lung cancer cells from non-small cell lung cancer patients to evaluate this nanocarrier system. Chitosan-coated poly(lactide-co-glycolide) (PLGA) nanoparticles were used to form oligonucleotide-nanoparticle-complexes (nanoplexes) with antisense 2-O-methyl-RNA (OMR) that can inhibit telomerase activity by binding to the RNA component of telomerase. OMR cellular uptake was strongly enhanced by nanoplexes mediated delivery in both, primary cells and tissue slices. More than 80% of primary cancer cells and 50% of cells in tissue slices showed OMR uptake. Telomerase activity was inhibited by approximately 45% in primary cancer cells and about 40% in tissue slices. Nanoplexes could penetrate into tumor tissue without influencing tissue architecture and the delivered OMR was able to inhibit telomerase activity with relatively low cytotoxicity.
Journal of Controlled Release
AAPS PharmSciTech, 2020
Non-invasive brain therapy for chronic neurological disorders is in high demand. Vinpocetine (VIN... more Non-invasive brain therapy for chronic neurological disorders is in high demand. Vinpocetine (VIN) tablets for cerebrovascular degenerative disorders ensued < 7% oral bioavailability. The olfactory pathway (providing direct brain access) can improve VIN pharmacokinetic/pharmacodynamic profile. In this context, VIN hydrogels based on temperature-, pH-, and ion-triggered gelation in physiological milieu were formulated. Poloxamer-chitosan (PLX-CS) and carbopol-HPMC-alginate (CP-HPMC-SA) systems were optimized for appropriate gelation time, temperature, and pH. PLX-CS-hydrogels exhibited strong mucoadhesion for > 8 h, while CP-HPMC-SA hydrogels were mucoadhesive in simulated nasal fluid, owing to pH and ion-activated gelation. Along with prolonged mucosal residence, hydrogels confirmed sustained VIN release (> 24 h), especially from CP-HPMC-SA hydrogels. As proof of concept, brain exposure of intranasal VIN hydrogels was investigated in rats versus VIN-IV bolus. PLX-CS provided 146% increase in AUC0-30 and 3-fold maximum brain concentration (BCmax) relative to IV bolus. BCmax was reached after 4 h versus 1 h (IV bolus). CP-HPMC-SA hydrogel showed superior brain targeting efficiency (460%) and brain direct transport percentage (78.23%). VIN plasma pharmacokinetics confirmed 45-60% reduction in AUCplasma versus IV bolus, while PCmax of CP-HPMC-SA and PLX-CS represented 17 and 28% that of IV bolus, respectively. Olfactory-targeted hydrogels grant effective, sustainable VIN brain level with minimal systemic exposure, thus, assuring lower dose, dose frequency, side effects, and per se better patient compliance.
British Journal of Pharmacy, 2019
is a potent lipid soluble photosensitizer having broad pharmacological spectrum. Its poor water s... more is a potent lipid soluble photosensitizer having broad pharmacological spectrum. Its poor water solubility leads to its aggregation in biological systems that diminishes its photodynamic activity (PDA) and its therapeutic applications. This study presents novel hydro-solving bilayer microneedle (MN) arrays incorporating Hy-loaded lipid nanocapsules (LNC) to prevent drug aggregation, enhance its delivery and local PDA. The Hy-LNC were prepared by a phase inversion technique and showed homogenous particle size distribution and high encapsulation efficiency (88.42 ± 0.11%). The bilayer MNs consist of a hydrogel cross-linked, drug free base plate and a Hy-loaded MN for onestep application. The dissolving MNs were fabricated from aqueous blends of 10% w/w poly vinyl alcohol and 30% w/w polyvinyl pyrrolidone by casting and pressure. The bilayer arrays showed good mechanical strength under a compression force of 32 N, with a height reduction of 10.14 ± 0.55% and sufficient insertion depth in both Parafilm M ® and excised porcine skin. After 2h of application to excised pig skin, the MNs were completely dissolved ensuring the delivery of their payload and the base plate was removed intact, free from MN residuals.
European Journal of Pharmaceutical Sciences, 2017
Myricetin-a natural flavonoid-has attracted a great interest due to its antioxidant and free-radi... more Myricetin-a natural flavonoid-has attracted a great interest due to its antioxidant and free-radical scavenging potential. However, its physicochemical instability critically impairs its dosage form design, evaluation and administration. In an attempt to protect from degradation, MYR was encapsulated into Gelucire-based solid lipid nanoparticles (SLNs). The impact of medium pH, processing temperature and different additives on the drug degradation either in free or nanoencapsulated form was assessed. MYR stability was further monitored in essential biorelevant fluids. Investigations have led to the recommendation that the presence of fat-soluble antioxidant is necessary during SLN preparation to protect the drug at high temperature. Meanwhile, physiological buffers as well as simulated fluids should be supplemented with stabilizers as tween 80 and poloxamer 407, in addition to water-soluble antioxidant such as sodium sulfite. Interestingly, mucin-containing fluids are suggested to provide better protection to MYR, in contrast, cell culture media do not guarantee MYR stability. The degradation kinetics changed from 1 st to 2 nd order mechanism after MYR nanoencapsulation. In presence of the aforementioned additives, MYR-SLNs significantly reduced the drug degradation rate constant up to 300-folds and prolonged the half-life time up to 4500-folds compared to free MYR in physiological buffers (Oneway ANOVA, p < 0.05). As a proof of concept, in vitro release experiment in presence of phosphate buffer (pH 7.4) supplemented with these additives ensured sustained release of MYR over > 8 h with no signs of degradation. The study emphasizes virtuous guidance regarding appropriate nanoencapsulation conditions and evaluation attributes ensuing MYR physicochemical stability.
Journal of Liposome Research, 2017
The present study investigates the effect of the preparation method (four methods) and formulatio... more The present study investigates the effect of the preparation method (four methods) and formulation additives (propylene glycol (PG) and cholesterol (CH)) on the entrapment efficiency (EE) of pyridoxine hydrochloride (vitamin B6 (VB6)), representing hydrophilic water-soluble low permeable vitamins, in unilamellar liposomes. The main aim is to compare determined EE with predicted values generated using a web-published, computational model. Results showed that among the different preparation methods, modified film hydration showed significantly higher EE (p50.05). With regard to formulation additives, PG (5% w/v) produced smaller vesicles size with narrow size distribution. Agreement between determined and model-generated EE values was more evident in formulae with narrow size distribution (polydispersity index (PdI) below 0.23). Formulae containing PG showed slightly higher determined than predicted EE values indicating vitamin-phospholipid bilayer interaction. Meanwhile, agreement between determined and predicted EE was limited to VB6-to-phospholipid ratio below (1.2:2). The comparison provided further insight into the usefulness of the prediction model factors affecting agreement between determined and predicted EE data.
Photodiagnosis and Photodynamic Therapy, 2016
Background: Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS)... more Background: Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS) with high fluorescence ability. Its use in photodynamic therapy (PDT) is hampered by hydrophobicity and poor biodistribution. Methods: AlPc was converted to a biocompatible nanostructure by incorporation into amphiphilic polyethylene glycol-polycaprolactone (PECL) copolymer nanoparticles, allowing efficient entrapment of the PS in the hydrophobic core, water dispersibility and biodistribution enhancement by PEG-induced surface characteristics. A series of synthesized PECL copolymers were used to prepare nanophotosensitizers with an average diameter of 66.5-99.1 nm and encapsulation efficiency (EE%) of 66.4-78.0%. One formulation with favorable colloidal properties and relatively slow release over 7 days was selected for in vitro photophysical assessment and in vivo biodistribution studies in mice. Results: The photophysical properties of AlPc were improved by encapsulating AlPc into PECL-NPs, which showed intense fluorescence emission at 687 nm and no AlPc aggregation has been induced after entrapment into the nanoparticles. Biodistribution of AlPc loaded NPs (AlPc-NPs) and free AlPc drug in mice was monitored by in vivo whole body fluorescence imaging and ex vivo organ imaging, with in vivo imaging system (IVIS). Compared to a AlPc solution in aqueous TWEEN 80 (2 w/v%), the developed nanophotosensitizer showed targeted drug delivery to lungs, liver and spleen as monitored by the intrinsic fluorescence of AlPc at different time points (1 h, 24 h and 48 h) post iv. administration. Conclusions: The AlPc-based copolymer nanoparticles developed offer potential as a single agentmultifunctional theranostic nanophotosensitizer for PDT coupled with imaging-guided drug delivery and biodistribution, and possibly also fluorescence diagnostics.
International Journal of Pharmaceutics, 2015
This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-solu... more This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol ($200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6 h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2 N and residence time of 4.4 h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of watersoluble vitamins. 2015 Elsevier B.V. All rights reserved.
International journal of pharmaceutics, Jan 10, 2015
Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is... more Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkab...
International Journal of Pharmaceutics, 2013
ABSTRACT
ABSTRACT Respiratory mucus is one of the main barriers for nanoparticle-based pulmonary delivery ... more ABSTRACT Respiratory mucus is one of the main barriers for nanoparticle-based pulmonary delivery systems. This holds true especially for lung diseases like cystic fibrosis, where a very tenacious thick mucus layer hinders particle diffusion to the lung epithelium or the target area. Typically, mean square displacement of particles is used for mobility evaluation. In contrast, our objective is to develop a feasible technique to track directed particle penetration as a prerequisite for efficient pulmonary nanotherapy. Therefore, particle diffusion in artificial mucus was monitored based on confocal laser scanning microscopy (CLSM) and particle-mucus interaction was observed. As pharmaceutical relevant and benign materials, solid lipid nanoparticles (SLNs) were prepared by hot-melt emulsification using glyceryl behenate and different stabilizing agents such as poloxamer-407, tween-80, and polyvinyl alcohol (PVA). The diffusion of labeled SLNs in stained artificial sputum representing CF-patient sputum was verified by 3D time laps imaging. Thus, the effect of coating, particle size and mucus viscosity on nanoparticle diffusion was studied. Using image analysis software "Image J", the total fluorescent signal after 30 min in case of poloxamer-coated SLNs was 5 and 100 folds higher than tween- and PVA-coated SLNs, respectively. Nevertheless, increasing mucus viscosity reduced the diffusion of tweencoated SLNs by a factor of 10. Studying particle-mucus interaction by CLSM can be considered a promising and versatile technique.
Nanotherapeutics - Drug Delivery Concepts in Nanoscience
... The contact time of the carrier systems with the membrane might increase uptake probability P... more ... The contact time of the carrier systems with the membrane might increase uptake probability Page 58. Transport Across Biological Barriers 45 [El-Shabouri, 2002; Hariharan et al, 2006]. ... 787-792. Bharali, DJ, Lucey, DW, Jayakumar, H., Pudavar, HE and Prasad, PN (2005). ...
Polymer-conjugate drug/protein Carbon nanotubes Nanocarriers for cancer therapy & detection Dendr... more Polymer-conjugate drug/protein Carbon nanotubes Nanocarriers for cancer therapy & detection Dendrimers Dendrimers Liposomes Liposomes Surface modified nanoparticles Surface modified nanoparticles Polymeric micelles Polymeric micelles Polymer-conjugate drug/protein Polymer-conjugate drug/protein Carbon nanotubes Carbon nanotubes Chapter 5 Cytotoxicity of chitosan-modified PLGA nanoparticles Relevance of the colloidal stability on the toxicity results* *This chapter has been submitted for publication as a journal article: N. Nafee, M. Schneider, U.F. Schäfer, and C.-M. Lehr. Relevance of the colloidal stability of chitosan-modified PLGA nanoparticles on their cytotoxicity profile. International Journal of Pharmaceutics. (submitted article) Chapter 5: Cytotoxicity of chitosan-modified PLGA nanoparticles
SUMMARY The hydrophobic nature of aluminium phthalocyanine causes its aggregation in biological f... more SUMMARY The hydrophobic nature of aluminium phthalocyanine causes its aggregation in biological fluids, thus abolishes its photoactivity and limits its biological application. Amphiphilic biodegradable block copolymers were synthesized and allowed to assemble in aqueous solution into nanoparticles (<100 nm). AlPc encapsulated in these polymeric nanoparticles exhibit better photodynamic activity, lower dark toxicity and prolonged release behavior compared to the free photosensitizer. Amphiphilic nanoparticles could be considered a promising carrier for hydrophobic photosensitizers.
SUMMARY Plain solid lipid nanoparticles (SLNs) were formulated by melt emulsification method usin... more SUMMARY Plain solid lipid nanoparticles (SLNs) were formulated by melt emulsification method using different lipids, fatty acids and waxes stabilized by polymeric emulsifying agents. The optimized nanoparticles were spherical in the size range of 100-200 nm with narrow size distribution as confirmed by polydispersity index (PDI < 0.2). SLNs were negatively charged with ζ-potential values between -3 and -18 mV. Amphiphilic lipids provided smaller and more stable SLNs compared to fatty acids and waxes. For the pulmonary delivery purposes, SLNs were nebulized using jet nebulizers. Results showed promising aerosol output rate as well as colloidal stability. INTRODUCTION Currently, lipid-based nanocarriers including SLNs and Nano-structured lipid carriers (NLCs) become an appealing advance in versatile pharmaceutical applications [1]. SLNs consist of nanosized solid lipid particles dispersed in aqueous medium. SLNs have the advantages of acquisition of biocompatible and biodegradable ...
European Journal of Pharmaceutics and Biopharmaceutics, 2018
Mucus-penetrating solid lipid nanoparticles for the treatment of cystic fibrosis: Proof of concep... more Mucus-penetrating solid lipid nanoparticles for the treatment of cystic fibrosis: Proof of concept, challenges and pitfalls,
Colloids and surfaces. B, Biointerfaces, Jan 10, 2015
A series of cyclodextrin-based star polymers were synthesized using β-cyclodextrin (CD) as hydrop... more A series of cyclodextrin-based star polymers were synthesized using β-cyclodextrin (CD) as hydrophilic core, methyl methacrylate (MMA) and tert-butyl acrylate (tBA) as hydrophobic arms. Star polymers, either homopolymers or random/block copolymers, showed narrow molecular weight distributions. Grafting hydrophobic arms created CD-based nanoparticles (CD-NPs) in the size range (130-200nm) with narrow PdI <0.15 and slightly negative ζ-potential. Particle surface could be modified with chitosan to impart a positive surface charge. Colloidal stability of CD-NPs was a function of pH as revealed by the pH-titration curves. CD-NPs were used as carrier for the chemotherapeutic drug idarubicin (encapsulation efficiency, EE ∼40%) ensuring prolonged release profile (∼80% after 48h). For cell-based studies, coumarin-6 was encapsulated as a fluorescent marker (EE ∼75%). Uptake studies carried out on A549 and Caco-2 cell lines proved the uptake of coumarin-loaded NPs as a function of time and ...
European Journal of Pharmaceutics and Biopharmaceutics, 2012
International Journal of Pharmaceutics, 2011
Nanoparticles delivery of oligonucleotides represents a potential approach for cancer treatment. ... more Nanoparticles delivery of oligonucleotides represents a potential approach for cancer treatment. However, most of the experiments were based on established cancer cell lines and may not reflect the original solid tumor in vivo. Both, tumor microenvironment and tumor cell biological properties in the tumor can influence the delivery efficiency of oligonucleotides. Therefore, it is important to understand the effect of nanoparticles delivery of oligonucleotides on tumor response in intact tissue architecture of individual tumors. We used freshly isolated human tumor tissue slices and primary lung cancer cells from non-small cell lung cancer patients to evaluate this nanocarrier system. Chitosan-coated poly(lactide-co-glycolide) (PLGA) nanoparticles were used to form oligonucleotide-nanoparticle-complexes (nanoplexes) with antisense 2-O-methyl-RNA (OMR) that can inhibit telomerase activity by binding to the RNA component of telomerase. OMR cellular uptake was strongly enhanced by nanoplexes mediated delivery in both, primary cells and tissue slices. More than 80% of primary cancer cells and 50% of cells in tissue slices showed OMR uptake. Telomerase activity was inhibited by approximately 45% in primary cancer cells and about 40% in tissue slices. Nanoplexes could penetrate into tumor tissue without influencing tissue architecture and the delivered OMR was able to inhibit telomerase activity with relatively low cytotoxicity.
Journal of Controlled Release
AAPS PharmSciTech, 2020
Non-invasive brain therapy for chronic neurological disorders is in high demand. Vinpocetine (VIN... more Non-invasive brain therapy for chronic neurological disorders is in high demand. Vinpocetine (VIN) tablets for cerebrovascular degenerative disorders ensued < 7% oral bioavailability. The olfactory pathway (providing direct brain access) can improve VIN pharmacokinetic/pharmacodynamic profile. In this context, VIN hydrogels based on temperature-, pH-, and ion-triggered gelation in physiological milieu were formulated. Poloxamer-chitosan (PLX-CS) and carbopol-HPMC-alginate (CP-HPMC-SA) systems were optimized for appropriate gelation time, temperature, and pH. PLX-CS-hydrogels exhibited strong mucoadhesion for > 8 h, while CP-HPMC-SA hydrogels were mucoadhesive in simulated nasal fluid, owing to pH and ion-activated gelation. Along with prolonged mucosal residence, hydrogels confirmed sustained VIN release (> 24 h), especially from CP-HPMC-SA hydrogels. As proof of concept, brain exposure of intranasal VIN hydrogels was investigated in rats versus VIN-IV bolus. PLX-CS provided 146% increase in AUC0-30 and 3-fold maximum brain concentration (BCmax) relative to IV bolus. BCmax was reached after 4 h versus 1 h (IV bolus). CP-HPMC-SA hydrogel showed superior brain targeting efficiency (460%) and brain direct transport percentage (78.23%). VIN plasma pharmacokinetics confirmed 45-60% reduction in AUCplasma versus IV bolus, while PCmax of CP-HPMC-SA and PLX-CS represented 17 and 28% that of IV bolus, respectively. Olfactory-targeted hydrogels grant effective, sustainable VIN brain level with minimal systemic exposure, thus, assuring lower dose, dose frequency, side effects, and per se better patient compliance.
British Journal of Pharmacy, 2019
is a potent lipid soluble photosensitizer having broad pharmacological spectrum. Its poor water s... more is a potent lipid soluble photosensitizer having broad pharmacological spectrum. Its poor water solubility leads to its aggregation in biological systems that diminishes its photodynamic activity (PDA) and its therapeutic applications. This study presents novel hydro-solving bilayer microneedle (MN) arrays incorporating Hy-loaded lipid nanocapsules (LNC) to prevent drug aggregation, enhance its delivery and local PDA. The Hy-LNC were prepared by a phase inversion technique and showed homogenous particle size distribution and high encapsulation efficiency (88.42 ± 0.11%). The bilayer MNs consist of a hydrogel cross-linked, drug free base plate and a Hy-loaded MN for onestep application. The dissolving MNs were fabricated from aqueous blends of 10% w/w poly vinyl alcohol and 30% w/w polyvinyl pyrrolidone by casting and pressure. The bilayer arrays showed good mechanical strength under a compression force of 32 N, with a height reduction of 10.14 ± 0.55% and sufficient insertion depth in both Parafilm M ® and excised porcine skin. After 2h of application to excised pig skin, the MNs were completely dissolved ensuring the delivery of their payload and the base plate was removed intact, free from MN residuals.
European Journal of Pharmaceutical Sciences, 2017
Myricetin-a natural flavonoid-has attracted a great interest due to its antioxidant and free-radi... more Myricetin-a natural flavonoid-has attracted a great interest due to its antioxidant and free-radical scavenging potential. However, its physicochemical instability critically impairs its dosage form design, evaluation and administration. In an attempt to protect from degradation, MYR was encapsulated into Gelucire-based solid lipid nanoparticles (SLNs). The impact of medium pH, processing temperature and different additives on the drug degradation either in free or nanoencapsulated form was assessed. MYR stability was further monitored in essential biorelevant fluids. Investigations have led to the recommendation that the presence of fat-soluble antioxidant is necessary during SLN preparation to protect the drug at high temperature. Meanwhile, physiological buffers as well as simulated fluids should be supplemented with stabilizers as tween 80 and poloxamer 407, in addition to water-soluble antioxidant such as sodium sulfite. Interestingly, mucin-containing fluids are suggested to provide better protection to MYR, in contrast, cell culture media do not guarantee MYR stability. The degradation kinetics changed from 1 st to 2 nd order mechanism after MYR nanoencapsulation. In presence of the aforementioned additives, MYR-SLNs significantly reduced the drug degradation rate constant up to 300-folds and prolonged the half-life time up to 4500-folds compared to free MYR in physiological buffers (Oneway ANOVA, p < 0.05). As a proof of concept, in vitro release experiment in presence of phosphate buffer (pH 7.4) supplemented with these additives ensured sustained release of MYR over > 8 h with no signs of degradation. The study emphasizes virtuous guidance regarding appropriate nanoencapsulation conditions and evaluation attributes ensuing MYR physicochemical stability.
Journal of Liposome Research, 2017
The present study investigates the effect of the preparation method (four methods) and formulatio... more The present study investigates the effect of the preparation method (four methods) and formulation additives (propylene glycol (PG) and cholesterol (CH)) on the entrapment efficiency (EE) of pyridoxine hydrochloride (vitamin B6 (VB6)), representing hydrophilic water-soluble low permeable vitamins, in unilamellar liposomes. The main aim is to compare determined EE with predicted values generated using a web-published, computational model. Results showed that among the different preparation methods, modified film hydration showed significantly higher EE (p50.05). With regard to formulation additives, PG (5% w/v) produced smaller vesicles size with narrow size distribution. Agreement between determined and model-generated EE values was more evident in formulae with narrow size distribution (polydispersity index (PdI) below 0.23). Formulae containing PG showed slightly higher determined than predicted EE values indicating vitamin-phospholipid bilayer interaction. Meanwhile, agreement between determined and predicted EE was limited to VB6-to-phospholipid ratio below (1.2:2). The comparison provided further insight into the usefulness of the prediction model factors affecting agreement between determined and predicted EE data.
Photodiagnosis and Photodynamic Therapy, 2016
Background: Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS)... more Background: Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS) with high fluorescence ability. Its use in photodynamic therapy (PDT) is hampered by hydrophobicity and poor biodistribution. Methods: AlPc was converted to a biocompatible nanostructure by incorporation into amphiphilic polyethylene glycol-polycaprolactone (PECL) copolymer nanoparticles, allowing efficient entrapment of the PS in the hydrophobic core, water dispersibility and biodistribution enhancement by PEG-induced surface characteristics. A series of synthesized PECL copolymers were used to prepare nanophotosensitizers with an average diameter of 66.5-99.1 nm and encapsulation efficiency (EE%) of 66.4-78.0%. One formulation with favorable colloidal properties and relatively slow release over 7 days was selected for in vitro photophysical assessment and in vivo biodistribution studies in mice. Results: The photophysical properties of AlPc were improved by encapsulating AlPc into PECL-NPs, which showed intense fluorescence emission at 687 nm and no AlPc aggregation has been induced after entrapment into the nanoparticles. Biodistribution of AlPc loaded NPs (AlPc-NPs) and free AlPc drug in mice was monitored by in vivo whole body fluorescence imaging and ex vivo organ imaging, with in vivo imaging system (IVIS). Compared to a AlPc solution in aqueous TWEEN 80 (2 w/v%), the developed nanophotosensitizer showed targeted drug delivery to lungs, liver and spleen as monitored by the intrinsic fluorescence of AlPc at different time points (1 h, 24 h and 48 h) post iv. administration. Conclusions: The AlPc-based copolymer nanoparticles developed offer potential as a single agentmultifunctional theranostic nanophotosensitizer for PDT coupled with imaging-guided drug delivery and biodistribution, and possibly also fluorescence diagnostics.
International Journal of Pharmaceutics, 2015
This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-solu... more This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol ($200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6 h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2 N and residence time of 4.4 h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of watersoluble vitamins. 2015 Elsevier B.V. All rights reserved.
International journal of pharmaceutics, Jan 10, 2015
Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is... more Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkab...
International Journal of Pharmaceutics, 2013
ABSTRACT
ABSTRACT Respiratory mucus is one of the main barriers for nanoparticle-based pulmonary delivery ... more ABSTRACT Respiratory mucus is one of the main barriers for nanoparticle-based pulmonary delivery systems. This holds true especially for lung diseases like cystic fibrosis, where a very tenacious thick mucus layer hinders particle diffusion to the lung epithelium or the target area. Typically, mean square displacement of particles is used for mobility evaluation. In contrast, our objective is to develop a feasible technique to track directed particle penetration as a prerequisite for efficient pulmonary nanotherapy. Therefore, particle diffusion in artificial mucus was monitored based on confocal laser scanning microscopy (CLSM) and particle-mucus interaction was observed. As pharmaceutical relevant and benign materials, solid lipid nanoparticles (SLNs) were prepared by hot-melt emulsification using glyceryl behenate and different stabilizing agents such as poloxamer-407, tween-80, and polyvinyl alcohol (PVA). The diffusion of labeled SLNs in stained artificial sputum representing CF-patient sputum was verified by 3D time laps imaging. Thus, the effect of coating, particle size and mucus viscosity on nanoparticle diffusion was studied. Using image analysis software "Image J", the total fluorescent signal after 30 min in case of poloxamer-coated SLNs was 5 and 100 folds higher than tween- and PVA-coated SLNs, respectively. Nevertheless, increasing mucus viscosity reduced the diffusion of tweencoated SLNs by a factor of 10. Studying particle-mucus interaction by CLSM can be considered a promising and versatile technique.
Nanotherapeutics - Drug Delivery Concepts in Nanoscience
... The contact time of the carrier systems with the membrane might increase uptake probability P... more ... The contact time of the carrier systems with the membrane might increase uptake probability Page 58. Transport Across Biological Barriers 45 [El-Shabouri, 2002; Hariharan et al, 2006]. ... 787-792. Bharali, DJ, Lucey, DW, Jayakumar, H., Pudavar, HE and Prasad, PN (2005). ...