Chitosan-Sodium Alginate Nanoparticles Research Articles

FORMULATION OF BINAHONG LEAVES (ANREDERA CORDIFOLIA) EXTRACT NANOPARTICLE AND EVALUATION OF IN VIVO ANTIDIABETIC ACTIVITY

Objective: Binahong leaves (Anredera cordifolia (Ten.) Steenis) is an herbal plant that is most commonly used to cure various types of diseases in Indonesia, including diabetes. The objective of this study was to conduct a comparative analysis of the antidiabetic activities between binahong leaves extract and binahong leaves extract nanoparticles. Methods: Nanoparticle formulation was carried out using chitosan and sodium alginate polymers as crosslinkers. DDY strain mice with 70% ethanol extract of binahong leaves as test material Binahong leaf extract was tested on alloxan-induced diabetic mice at a dose of 200 mg/kgBW intraperitoneally. The dose of binahong extract used was 200 mg/kgBB and 200 mg/kgBB of chitosan-sodium alginate nanoparticles orally for 14 ds. Results: Obtained extract nanoparticle met the specification, with average sizes of 192.7 nm, zeta potential of+25.3 mV. Extract nanoparticle with a dose equivalent to 200 mg/kgBB binahong leaf extract can reduce blood glucose levels in mice induced by alloxan was better than binahong leaf extract at a dose 200 mg/kgBW with respective percent reduction in blood glucose levels are 45.89% and 33.38%. Conclusion: The formulated extract nanoparticle can enhance the antidiabetic activity of binahong leaves extract.

Modulation the Synergistic Effect of Chitosan-Sodium Alginate Nanoparticles with Ca2+: Enhancing the Stability of Pickering Emulsion on D-Limonene.

Pickering emulsions (PEs) have been regarded as an effective approach to sustaining and preserving the bioactivities of essential oils. The aim of this research is to prepare a PE stabilized by chitosan/alginate nanoparticles (CS-SA NPs) for the encapsulation and stabilization of D-limonene. In this work, the influence of calcium ions (Ca2+) on the morphology and interaction of nanoparticles was studied, and then the preparation technology of CS-SA/Ca2+ NPs was optimized. The results showed that the presence of Ca2+ reduced the size of the nanoparticles and made them assume a spherical structure. In addition, under the conditions of 0.2 mg/mL CaCl2, 0.6 mg/mL SA, and 0.4 mg/mL CS, the CS-SA/Ca2+ NPs had the smallest size (274 ± 2.51 nm) and high stability (-49 ± 0.69 mV). Secondly, the PE was prepared by emulsifying D-limonene with CS-SA/Ca2+ NPs, and the NP concentrations and homogenization speeds were optimized. The results showed that the small droplet size PE could be prepared with 2 mg/mL NP and a homogenization speed of 20,000 r/min, and it had excellent antibacterial and antioxidant activities. Most importantly, the emulsion showed higher activity, higher resistance to ultraviolet (UV) and a higher temperature than free D-limonene. This research provides a feasible solution for the encapsulation, protection and delivery of essential oils.

Preparation of Nanoparticles Loaded with Quercetin and Effects on Bacterial Biofilm and LPS-Induced Oxidative Stress in Dugesia japonica.

Quercetin is a kind of flavonol compound, which has been widely concerned because of its good pharmacological effects. However, its poor water solubility and poor oral absorption limit its application. To address the above problems, the optimal technological conditions for preparing quercetin-loaded chitosan sodium alginate nanoparticles (Q-CSNPs) were obtained through single-factor experiment method. Q-CSNPs were characterized by particle size analyzer, scanning electron microscope (SEM), transmission electron microscope (TEM), and Fourier transform infrared spectroscopy (FTIR). Biofilm experiment evaluated the antibacterial activity of five different concentrations of Q-CSNPs against Escherichia coli and Staphylococcus aureus. DPPH and hydroxyl radical scavenging experiments determined their antioxidant activity. The effect of Q-CSNPs labeled with FITC on the oxidative stress of planarian was determined. The results showed that quercetin was successfully encapsulated and had good antibacterial and antioxidant capacity in vitro. In vivo experiments of planarians also showed that Q-CSNPs could inhibit the oxidative stress induced by lipopolysaccharide (LPS) and especially alleviate the decrease of CAT activity and the increase of MDA content in planarians induced by LPS. After being supported by future in vivo studies, this preparation will provide research possibilities for the development of quercetin nano-drugs, quercetin dietary supplement, and so on.

Resolving male infertility that is induced by β-and ca channel antagonist drugs: Propranolol/Verapamil using an optimized nanohybrid formula: Experimental and computational studies

Two major objectives of the current study, the first was to study theoretically the electronic structure of Chitosan-Sodium alginate, Epigallocatechin-gallate (EGCG) and Sodium alginate-EGCG complex using density-functional theory (DFT) calculations. The binding energy (ΔEbind), the atoms in molecules (AIM) theory and the Natural bond orbital (NBO) analysis of Chitosan-Sodium alginate-EGCG complex have been studied in gas and water phases. The second was to investigate the treatment effect of EGCG in normal form and EGCG-loaded chitosan-sodium alginate nanoparticles (EGCG-CS-SA NPs) on the male infertility that was induced in male albino rats by the oral administration of Propranolol Hydrochloride and Verapamil Hydrochloride. Full characterization of the synthesized EGCG-CS-SA NPs were carried out using different techniques. Then eight groups of rats were classified as follows: control negative (A); Propranolol Hydrochloride (B); Verapamil Hydrochloride (C); EGCG normal (D); EGCG nano (EGCG-CS-SA NPs) (E); Propranolol Hydrochloride + EGCG (F); Propranolol Hydrochloride + EGCG-CS-SA NPs (G); and Verapamil Hydrochloride + EGCG-CS-SA NPs (H). The study registered the body weight gain percentage as well the weights of the liver, testes, and seminal vesicles. Malondialdehyde (MDA), glutathione reduced (GSH), and testosterone levels were assessed. The semen analysis was performed, the deoxyribonucleic acid (DNA) damage was detected, and the histopathological sections were examined. The computational study identified that the interaction between chitosan-sodium alginate and EGCG is covalent and electrostatic interactions in nature in the gas and water phases. The results recorded an increase in body weight gain percentage in Propranolol Hydrochloride + EGCG-CS-SA NPs and Verapamil Hydrochloride + EGCG-CS-SA NPs groups but no significant difference (P› 0.05) in organs weight of experimental groups (B, C, D, E, F, G, and H) as compared to control group. In the treated rats (F, G, and H), the MDA decreased significantly, while the GSH increased.The results showed that the formula improved the negative effects of Propranolol Hydrochloride and Verapamil Hydrochloride administration on serum testosterone level, sperm count, motility, percentage of live sperms, and histological structures in the testes and epididymides. Post-administration of EGCG normal and EGCG-CS-SA NPs to Propranolol Hydrochloride and Verapamil Hydrochloride caused no significant difference (P› 0.05) in tail moment value in testes cells as compared to Propranolol Hydrochloride and verapamil Hydrochloride groups. Finally, the herbal nanohybrid formula EGCG-CS-SA NPs was found to be safe and could be used to treat male infertility caused by antihypertensives.

Treatment of Brucellosis in Guinea Pigs via a Combination of Engineered Novel pH-Responsive Curcumin Niosome Hydrogel and Doxycycline-Loaded Chitosan-Sodium Alginate Nanoparticles: an In Vitro and In Vivo Study.

Brucellosis is a common zoonotic infection, particularly in the developing world. The recommended treatment regimens for brucellosis involve the use of two medications such as doxycycline and curcumin in order to avoid relapses and prolonged use of these drugs. Doxycycline has excellent activity in the acidic phagolysosomal environment, while curcumin modulates the immune system function and macrophage activity. Due to the intracellular existence of Brucellae and the different anti-immune mechanisms of Brucella, the treatment of Brucella infection faces many limitations. The design of nanosystems is a promising treatment approach for brucellosis. The objective of this study was to design and evaluate the efficacy of in situ pH-responsive curcumin-loaded niosome hydrogel and doxycycline-loaded chitosan-sodium alginate nanoparticles as chemotherapeutic agents against brucellosis. The prepared formulae showed a spherical nano shape with a slow drug release pattern and small particle size. The prepared formulae were evaluated in vivo using Guinea pigs experimentally infected with Brucella melitensis biovar3. The prepared formula combination gave a significant high reduction rate of Brucella spleen viable count compared with that of untreated controls at p < 0.05. The results showed that the treatment schemes were not fully successful in eliminating Brucella infection in Guinea pigs; however, they significantly (p < 0.05) reduced the viable Brucella count in a shorter time and sub-therapeutic doses. Collectively the novel prepared formulae could be a successful therapy for the effective treatment of brucellosis infection at the recommended therapeutic doses. Graphical abstract.

Quality by design (Qbd) approach to develop stability indicating HPLC method for estimation of rutin in chitosan-sodium alginate nanoparticles

Rutin is a flavonoid glycoside, mainly consists of phenolic compounds, responsible for many biological activities. The objective of the present study was to develop and validate a precise, simple, robust, rapid and reliable reverse phase high -performance liquid chromatography (RP-HPLC) technique by using Qbd approach for evaluating the rutin in nanoparticles. Central composite design (CCD) was employed for optimizing the experimental conditions of RP-HPLC method. Buffer pH, methanol content in the mobile phase composition, flow rate, and wavelength were selected as independent variables whereas retention time, peak area, and asymmetry factor was selected as dependent variables. The retention time, peak area and asymmetric factor of rutin by using optimized independent variables were found to be 3.75 min, 1014.79 mV, and 1.26 respectively. The limit of detection and limit of quantitation values were found to be 0.005 µg/mL and 0.15 µg/mL respectively. For confirming linearity, accuracy, precision, and robustness, the optimized assay condition was validated as per ICH guidelines. The proposed method, which was optimized by QbD approach was found to be a suitable method for analyzing the rutin in chitosan-sodium alginate nanoparticles.

Chitosan-alginate nano-carrier for transdermal delivery of pirfenidone in idiopathic pulmonary fibrosis

Pirfenidone (PFD) is one of the pyridine family components with anti-inflammatory, antifibrotic effects and US FDA approved for the treatment of idiopathic pulmonary fibrosis (IPF). Presently, PFD is administered orally and this has setbacks. Hence, it is important to eliminate the pharmacotherapeutic limitations of PFD. This research was carried out to study the possibility of transdermal delivery of PFD using chitosan-sodium alginate nanogel carriers. In order to synthesize chitosan-sodium alginate nanoparticles loaded with PFD, the pre-gelation method was used. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR) analyses were used for the characterization. Drug encapsulation and release manner were studied using UV spectroscopy. Ex vivo permeation examinations were performed using Franz diffusion cell and fluorescence microscopy. The results showed that nanoparticles having spherical morphology and size in the range of 80 nm were obtained. In vitro drug release profile represents sustained release during 24 h, while 50% and 94% are the loading capacity and efficiency, respectively. Also, the skin penetration of PFD loaded in nanoparticles was significantly increased as compared to PFD solution. The obtained results showed that synthesized nanoparticles can be considered as promising carriers for PFD delivery.

Chitosan-sodium alginate nanoparticle as a delivery system for ε-polylysine: Preparation, characterization and antimicrobial activity

ε-Polylysine-loaded chitosan-sodium alginate nanoparticles (ε-PL NPs) were synthesized and characterized in terms of particle size distribution, surface morphology, thermal properties and structure, respectively. Their antibacterial activity on Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Micrococcus luteus were studied. The ε-PL NPs were well dispersed as spherical particles within the range of 200–500 nm. In vitro release studies showed an initial burst release of ε-PL from the nanoparticles followed by a sustained release. The minimum inhibitory concentrations (MIC) of ε-PL NPs against four test bacteria were 7.81 μg/mL (E. coli), 31.25 μg/mL (B. subtilis), 15.63 μg/mL (S. aureus) and 38.67 μg/mL (M. luteus), respectively. The bacteriostatic activity of ε-PL NPs was three times higher (P < 0.05) than that of free ε-PL in terms of inhibition zone diameter, suggesting that ε-PL NPs has stronger antibacterial activity. These findings may provide some basis for the application of ε-PL NPs as a promising food preservative.

English

Management of rheumatic disorders are limited by the inability to provide long-term drug delivery due to the irritation to gastric mucosa and poor availability of drugs, which may be overcome by prolonging the drug release. The nanostructured carriers (NP)based gel was developed as potential topical system for aceclofenac topical delivery. In the present study, chitosan-sodium alginate nanoparticles were investigated using a novel gel base for the prolonged topical delivery NSAID aceclofenac. A modified ionotropic gelation method was used to produce aceclofenac loaded nano particulate systems. Drug content, particle properties such as size, size distribution and zeta potential were determined. The nano particulate system was encapsulated using a novel hydrophilic polymer pemulen in different proportions. The nanoparticles remained within the colloidal range and it was uniformly dispersed in pemulen gel preparation. The gels were evaluated for spredability, extrudability and in vitro, in vivo studies. The optimized formulations were characterized by FT-IR, DSC. In conclusion, nanoparticle based gel could be a promising vehicle for topical delivery of aceclofenac and the novel gel base pemulen can be used for the incorporation topical drugs. Key words: Pemulen, aceclofenac, sodium alginate, transdermal, chitosan, nanoparticle, topical delivery, gel.

Formulation and Evaluation of Betamethasone Sodium Phosphate Loaded Nanoparticles for Ophthalmic Delivery

Betamethasone sodium phosphate is a potent glucocorticoid with anti-inflammatory activity and can be used in treatment of macular edema. The aim of this work is to formulate and investigate mucoadhesive chitosan-sodium alginate nanoparticles as new vehicle for the prolonged topical ophthalmic delivery of betamethasone sodium phosphate. Ionotropic gelation method was used to produce betamethasone loaded chitosan alginate nanoreservoir system. The effect of changing different formulation parameters (pH of chitosan solution, sodium alginate concentration, calcium chloride concentration, chitosan concentration, drug concentration and the addition of tween 80) on the physicochemical properties and in vitro release of the drug loaded nanoparticles was studied. The mean particle size ranged from 16.8 to 692 nm and the zeta potential generally ranged from +18.49 to +29.83 mV depending on the formulation conditions. The highest encapsulating efficiency obtained was 64%. In vitro release studies showed an initial burst release of the drug followed by slow sustained release over 24, 48 or 72 hours depending on the formulation parameters. The in vivo studies carried out for two selected formulations showed the release of 84%, 59.5% of the drug over 12 hours for both F3C and F12 respectively. The results of physicochemical properties of F3C and F12 upon storage showed good stability at both 25°C and 40°C as the drug content was within the accepted range, the pH was (5–7) and the mean particle size for both formulations over the three months was still interesting for ophthalmic application. The results of this study suggest that chitosan alginate nanoparticles would be a promising system for the sustained release delivery of betamethasone sodium phosphate to the posterior segment of the eye.

Chitosan–sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: Formulation, optimisation and in vitro characterisation

Management of extraocular disease is mainly limited by the inability to provide long-term extraocular drug delivery without avoiding the systemic drug exposure and/or affecting the intraocular structures and poor availability of drugs, which may be overcome by prolonging the contact time with the ocular surface, for instance with bioadhesive polymers. In the present study, mucoadhesive chitosan (CS)-sodium alginate (ALG) nanoparticles were investigated as a new vehicle for the prolonged topical ophthalmic delivery of antibiotic, gatifloxacin. A modified coacervation or ionotropic gelation method was used to produce gatifloxacin-loaded submicroscopic nanoreservoir systems. It was optimised using design of experiments by employing a 3-factor, 3-level Box-Behnken statistical design. Independent variables studied were the amount of the bioadhesive polymers: CS, ALG and the amount of drug in the formulation. The dependent variables were the particle size, zetapotential, encapsulation efficiency and burst release. Response surface plots were drawn, statistical validity of the polynomials was established and optimised formulations were selected by feasibility and grid search. Nanoparticles were characterised by FT-IR, DSC, TEM and atomic force microscopy. Drug content, encapsulation efficiency and particle properties such as size, size distribution (polydispersity index) and zetapotential were determined. The designed nanoparticles have average particle size from 205 to 572 nm (polydispersity from 0.325 to 0.489) and zetapotential from 17.6 to 47.8 mV. Nanoparticles revealed a fast release during the first hour followed by a more gradual drug release during a 24-h period following a non-Fickian diffusion process. Box-Behnken experimental design thus facilitated the optimisation of mucoadhesive nanoparticulate carrier systems for prolonged ocular delivery of the drug.