Formulation, optimization and characterization of allantoin-loaded chitosan nanoparticles to alleviate ethanol-induced gastric ulcer: in-vitro and in-vivo studies (original) (raw)
Related papers
International Journal of Nanomedicine
Background: Apocynin (APO) is a bioactive phytochemical with prominent antiinflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NP s) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NP s formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NP s provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NP s could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.
International Journal of Nanomedicine, 2015
Natural products using plants have received considerable attention because of their potential to treat various diseases. Arrabidaea chica (Humb. & Bonpl.) B. Verlot is a native tropical American vine with healing properties employed in folk medicine for wound healing, inflammation, and gastrointestinal colic. Applying nanotechnology to plant extracts has revealed an advantageous strategy for herbal drugs considering the numerous features that nanostructured systems offer, including solubility, bioavailability, and pharmacological activity enhancement. The present study reports the preparation and characterization of chitosan-sodium tripolyphosphate nanoparticles (NPs) charged with A. chica standardized extract (AcE). Particle size and zeta potential were measured using a Zetasizer Nano ZS. The NP morphological characteristics were observed using scanning electron microscopy. Our studies indicated that the chitosan/sodium tripolyphosphate mass ratio of 5 and volume ratio of 10 were found to be the best condition to achieve the lowest NP sizes, with an average hydrodynamic diameter of 150±13 nm and a zeta potential of +45±2 mV. Particle size decreased with AcE addition (60±10.2 nm), suggesting an interaction between the extract's composition and polymers. The NP biocompatibility was evaluated using human skin fibroblasts. AcE-NP demonstrated capability of maintaining cell viability at the lowest concentrations tested, stimulating cell proliferation at higher concentrations. Antiulcerogenic activity of AcE-NP was also evaluated with an acute gastric ulcer experimental model induced by ethanol and indomethacin. NPs loaded with A. chica extract reduced the ulcerative lesion index using lower doses compared with the free extract, suggesting that extract encapsulation in chitosan NPs allowed for a dose reduction for a gastroprotective effect. The AcE encapsulation offers an approach for further application of the A. chica extract that could be considered a potential candidate for ulcer-healing pharmaceutical systems.
Highlighting the impact of chitosan on the development of gastroretentive drug delivery systems
International Journal of Biological Macromolecules, 2020
The development of gastroretentive systems have been growing lately due to the high demand for carriers that increase drug bioavailability and therapeutic effectiveness after oral administration. Most of systems reported up to now are based on chitosan (CS) due to its peculiar properties, such as cationic nature, biodegradability, biocompatibility and important mucoadhesiveness, which make CS a promising biopolymer to design effective gastroretentive systems. In light of this, we reported in this review the CS versatility to fabricate different types of nano-and microstructured gastroretentive systems. For a better understanding of the gastric retention mechanisms, we highlighted expandable, density-based, magnetic, mucoadhesive and superporous systems. The biological and chemical properties of CS, anatomophysiological aspects related to gastrointestinal tract (GIT) and some applications of these systems are also described here. Overall, this review may assist researchers to explore new strategies to design safe and efficient gastroretentive systems in order to popularize them in the treatment of diseases and clinical practices.
Evidence-Based Complementary and Alternative Medicine
Due to an unhealthy lifestyle, gastric ulcers have become a very common disease these days. Moreover, the side effects linked with the prolonged use of conventional treatments have shifted the paradigm towards herbal therapies. The leaves of Morus alba L. (Family-Moraceae) have been traditionally used for a large number of metabolic diseases. In the present research, we focused on the development of chitosan microspheres using extracts of leaves of Morus alba L. and their evaluation for gastroprotective efficacy against ethanol-induced ulcers in experimental rats. The process of development of M. alba extract microsphere (MEM) is also optimized using the Box-Behnken design. The formulation was prepared at optimized conditions (chitosan concentration (1.66% w/w), volume of glutaraldehyde (4.69 mL), and stirrer rotation per minute, RPM, 854.8), and the percentage yield (Y1) of the resulted microspheres is ∼95% with an encapsulation efficiency (EE) of (Y2(rutin)) ∼86%, Y2(quercetin)) ∼...
The potential utility of chitosan micro/nanoparticles in the treatment of gastric infection
Expert Review of Anti-infective Therapy, 2014
Gastric infections are mainly caused by Helicobacter pylori (H. pylori), a bacterium that colonizes the gastric mucosa of over 50% of the world's population. Chronic H. pylori infection has been associated with gastric diseases such as chronic gastritis, peptic ulcer and gastric adenocarcinoma. Current eradication treatment relies on antibiotic-based therapies that are unsuccessful in approximately 20% of the patients. Chitosan, a natural and cationic polysaccharide has been investigated in the treatment of H. pylori infection. Due to its mucoadhesive properties, it has been used in the form of micro/nanoparticles, polyelectrolyte complexes or coatings as antibiotic encapsulation systems for gastric delivery, but alternative molecules may also be incorporated. It has been recently proposed that chitosan can also be used for H. pylori binding and scavenging from the host stomach due to its antimicrobial/ binding properties. In this manuscript, a brief description of the use of chitosan in H. pylori treatment is reviewed.
Study of Antiulcer activity of a hydrogel based on chitosan
Research Journal of Pharmacy and Technology, 2021
In this study, the antiulcer activity of a gel based on high-viscosity chitosan was studied in models of NSAID and ethanol-induced ulcerogenesis. To simulate damage to the gastric mucosa in the NSAID model, diclofenac sodium was administered to experimental animals at a dose of 50mg/kg. An antiseptic intestinal and astringent agent was chosen as reference drug: bismuth tripotassium dicitrate at a dose of 0.017g/kg. The studied gel was used in 3 doses (0.08, 0.16 and 0.24ml/100g of body weight). In ethanol model, ulcers were induced by a single administration of ethanol 96% at a dose of 5ml/kg. Omeprazole at a dose of 20mg/kg was used as reference drug in this model. Chitosan-based gel was administrated in this model at a dose of 0.16ml per 100g of animals, which corresponds to the minimum available dose with antiulcer activity in the NSAID model. All investigated substances were injected intragastrically using a gastric tube. As a result of this research, it was found that the chitosan-based gel is effective in the NSAID gastropathy model but not effective in the ethanol model. In the NSAID gastropathy model, after a single oral administration of chitosan-based gel at doses of 0.16 and 0.24ml/ 100g, sufficient antiulcer activity was revealed, which was 2.4 and 4.694, respectively, and exceeded the effect of the reference drug, bismuth tripotassium dicitrate. In the ethanol model, the results of experimental studies showed that the reference drug, omeprazole, provides antiulcer activity with a calculated value of the antiulcer activity index of 2.18. After the administration of a chitosan-based gel at a dose of 0.16 ml per 100g of body weight of animals, compared with the control, the calculated value of antiulcer activity was 1.18, which characterizes the absence of an antiulcer effect.
Gastrointestinal Delivery of APIs from Chitosan Nanoparticles
Chitin and Chitosan - Physicochemical Properties and Industrial Applications [Working Title], 2020
Successful clinical treatment outcomes rely on achieving optimal systemic delivery of therapeutics. The oral route of administering Active Pharmaceutical Ingredients (API) remains formidable because of ease to the patient and convenience. Yet, the gastrointestinal tract (GIT) poses several barriers that need to be surmounted prior to systemic availability, especially for Class IV type drugs. Drug delivery systems in the form of nanoparticles (NP), can be appropriately formulated to alter the physicochemical properties of APIs, thereby addressing constraints related to absorption from the GIT. Polymers offer amenability in the fabrication of NP due to their diversity. Chitosan has emerged as a strong contender in orally deliverable NP because it is biocompatible, biodegradable and muco-adhesive. Due to the positively charged amine moieties within chitosan (NH3+), interactions with the negatively charged sialic acid of mucin within the mucosa is possible, which favors delayed GI trans...
Metabolites
This study reported the fabrication and characterization of gastric dressing, composed of gelatine (GEL), chitosan (CH), and pomegranate peel (PP) extract. The structural changes occurring after γ-irradiation of GEL–CH–PP dressing were reported. The results showed that the electron paramagnetic resonance (EPR) spectroscopy of un-irradiated GEL–CH–PP showed two paramagnetic centers, which corresponded to g = 2.19 and g = 2.002. After irradiation, a new active centre appeared at g = 2.0035 at 10 kGy. The Fourier transform infrared spectroscopy (FTIR) analyses revealed an increase in peak intensity at C–H chains, as well as the C=O carboxyl groups at 10 kGy, due to the cross-linking phenomenon. The X-ray diffraction analysis showed a low change of crystallinity between the range of 2θ (15–30°). Moreover, γ-rays enhanced scavenging DPPH radical activity (51±%) and chelating power activities 79.12%. A significant inhibition of antibacterial and anti-biofilm activities (p < 0.01) was n...
Chitosan-based nanoparticles: An overview of biomedical applications and its preparation
Journal of Drug Delivery Science and Technology, 2019
Chitosan (CS) is one of the most successfully developed biodegradable polymers. Among the numerous polymers developed to formulate polymeric nanoparticles, CS has fascinated considerable attention due to its appealing properties: (i) biodegradability and biocompatibility, (ii) FDA approval for wound dressings as well as in dietary application, (iii) non-toxicity (v) scope of sustained release, (vi) probability to modify surface properties and (vii) scope of target nanoparticles (NPs) to particular organs or cells. This review presents different preparation methods of chitosan nanoparticles (CSNPs) from the methodological and mechanistic point of view. The crosslinking agent including aldehyde, tripolyphosphate (TPP), genipin and other cross linkers and the physicochemical behaviour of CSNPs including drug loading, drug release, particles size, zeta-potential and stability are briefly discussed. This review also presents why CS has been chosen to design nanoparticles (NPs) as drug delivery systems in various pharmaceutical applications.
Antimicrobial and Hepatoprotective Effect of Chitosan Nanoparticles In-vitro and In-vivo Study
Journal of Pharmaceutical Research International
Nanotechnology has become an extensive area of study due to the peculiar properties of nanoparticles. Chitosan is considered the most promising material for future applications. The purpose of this study was to highlight the antimicrobial and hepatoprotective properties of Chitosan nanoparticles (CTS), as well as their efficacy against multidrug-resistant pathogens and various applications as a natural antioxidant in the biomedical field. CTS were prepared with or without surfactant (L—lecithin, Tween 80) based on inotropic gelation of chitosan with sodium alginate. The nanoparticle obtained displayed a spherical shape with a particle size ranging from 54.3±20.8 to 1256±16.8 nm, zeta potential ranging from 24±1.2 to 30.8±1.1 mV, and polydispersity index ranging from 0.274±0.09 to 0.553±0.06. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) calculations were used to evaluate the antibacterial activity of CTS against four human pathogens: Bacillus su...