Chitosan-alginate Nanoparticles Research Articles

Sodium Triphosphate Effect on Encapsulation of Vitamin B<sub>6</sub> into Chitosan-Alginate Nanoparticles and Its <i>In Vitro</i> Drug Release Study

The in-vitro drug release study of vitamin B6 encapsulated into sodium tripolyphosphate crosslinked chitosan-alginate (B6-TCA) nanoparticles aims to determine the effect of sodium tripolyphosphate on the encapsulation efficiency of vitamin B6 and effectiveness of the nanoparticles to release vitamin B6. The focus of this research is synthesizing and characterizing TCA nanoparticles to encapsulate vitamin B6 as an effective delivery system by studying the kinetics release of vitamin B6. The research resulted in the formation of coarse solid powder nanoparticles in yellowish-white color with a nanoparticle size of 22.55 nm. Sodium tripolyphosphate decreased the percentage of encapsulation efficiency in the B6-TCA nanoparticles as its concentration increased. However, the increasing sodium tripolyphosphate causes a slower release of vitamin B6 from nanoparticles. The encapsulation efficiency of vitamin B6 is 82.04%. The optimum composition of B6-TCA nanoparticles ratio is 2:1:1.5:2, where Korsmeyer-Peppas kinetics model suited its better with the Fickian diffusion mechanism of 0.989 and has the smallest reaction rate constant of 0.039 occurred within 6 h.

Oral administration of encapsulated catechin in chitosan-alginate nanoparticles improves cognitive function and neurodegeneration in an aluminum chloride-induced rat model of Alzheimer's disease.

The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl3)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl3 treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl3 + Catechin), and treatment group 2 (AlCl3 + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl3 induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl3 was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.

Chitosan Alginate Nanoparticles of Protein Hydrolysate from Acheta domesticus with Enhanced Stability for Skin Delivery.

This study aimed to develop chitosan alginate nanoparticles (CANPs) for enhanced stability for dermal delivery of protein hydrolysate from Acheta domesticus (PH). CANPs, developed using ionotropic pre-gelation followed by the polyelectrolyte complex technique, were characterized for particle size, polydispersity index (PDI), and zeta potential. After the incorporation of PH into CANPs, a comprehensive assessment included encapsulation efficiency, loading capacity, morphology, chemical analyses, physical and chemical stability, irritation potential, release profile, skin permeation, and skin retention. The most optimal CANPs, comprising 0.6 mg/mL sodium alginate, 1.8 mg/mL calcium chloride, and 0.1 mg/mL chitosan, exhibited the smallest particle size (309 ± 0 nm), the narrowest PDI (0.39 ± 0.01), and pronounced negative zeta potential (-26.0 ± 0.9 mV), along with an encapsulation efficiency of 56 ± 2%, loading capacity of 2.4 ± 0.1%, release of 40 ± 2% after 48 h, and the highest skin retention of 12 ± 1%. The CANPs induced no irritation and effectively enhanced the stability of PH from 44 ± 5% of PH remaining in a solution to 74 ± 4% after three-month storage. Therefore, the findings revealed the considerable potential of CANPs in improving PH stability and skin delivery, with promising applications in cosmetics and related fields.

Comparative survival study of Bacillus coagulans and Enterococcus faecium microencapsulated in chitosan-alginate nanoparticles in simulated gastrointestinal condition

Probiotics have poor gastrointestinal delivery because they lose their viability during intestinal passage. Microencapsulation has a significant effect on the survival of probiotic bacteria. This study aimed to synthesize chitosan-alginate nanoparticles and encapsulate Bacillus coagulans NBRC-12583 and Enterococcus faecium MGFR1 in alginate (Alg), chitosan (Cht) and inulin (Inu) by micro- and nano-encapsulation to investigate the viability of encapsulated strains in simulated gastrointestinal condition. The survival of free and encapsulated bacteria was studied for 120 min. The population of B. coagulans encapsulated in Cht-Alg only decreased by 0.86 log CFU, while that of E. faecium encapsulated in Cht-Alg nanoparticles only decreased by 0.27 log CFU. Treated with simulated intestinal fluid, B. coagulans and E. faecium populations decreased by 1.03 and 0.17 log CFU, respectively. E. faecium microencapsulated in Cht-Alg and Inu had a maximum encapsulation efficiency of 96.78%. E. faecium encapsulated in Cht-Alg nanoparticles and Inu was more viable than other encapsulated bacteria. Scanning electron microscopy was done to investigate the microcapsules' surface morphology, structure, internal cross-sectional view, and the zeta potential for the surface charge of Cht-Alg nanoparticles. The viability of the probiotic bacteria was enhanced significantly by microencapsulation and nanomaterial-based encapsulation within the chitosan-alginate and inulin matrix.

Design and optimization of chitosan-alginate nanoparticles for plant growth hormone indole-3-acetic acid

Excessive use of agrochemicals can lead to environmental degradation, and thus, a potential solution is to control their release using biodegradable polymeric nanoparticles. This study aimed to fabricate indole-3-acetic acid chitosan/alginate nanoparticles (IAA-CANPs) through o/w emulsification and ionotropic gelation, employing a Box-Behnken design (BBD) to evaluate the influence of various factors (alginate: chitosan mass ratio (ALG:CS), TweenTM 80, and IAA concentration) on particle size, zeta potential, and encapsulation efficiency (EE). Response surface methodology (RSM) was used to determine the optimum conditions for nanoparticle fabrication, which were ALG:CS mass ratio of 1:0.10, TweenTM 80 of 1.5% w/v, and IAA of 15 mg/mL. The IAA-CANPs produced under these optimal conditions exhibited an average particle size of 275 ± 19 nm, a polydispersity index (PDI) of 0.37 ± 0.9, a zeta potential of -23.8 ± 0.8 mV, and an EE of 68.5 ± 1.4%. The IAA-CANPs also demonstrated superior physico-chemical stability under UV irradiation exposure compared to free IAA. The IAA-CANPs had stability up to 3 months at 4°C. The release pattern in dissolution media at pH 5.5 and 7.5 indicated a sustained-release behavior, which fit well with the Peppas-Sahlin kinetic model, indicating anomalous diffusion, a non-Fickian diffusion mechanism. These findings suggest that CANPs could be a promising approach for encapsulating and controlling the release of IAA, exhibiting excellent physicochemical stability and potential for agricultural applications.

Economic and Productive Comparison of Rutin and Rutin-Loaded Chitosan Alginate Nanoparticles Against Lead-Induced Oxidative Stress in Cobb and Arbor Broiler Breeds

Rutin, a natural bioflavonoid compound, is one of the best-known antioxidants. This study aimed to investigate the protective effect of rutin-loaded chitosan alginate nanoparticles (RCA NPs) against lead (Pb)-induced oxidative stress in two different broiler breeds. A total number of 240 chicks from Cobb (CB) and Arbor Acres (AR) breeds were randomly allocated into 4 groups/breed. The 1st group received standard basal diet (SD) and drinking water (DW) while the 2nd group received SD and Pb-incorporated DW (350 mg/L). The 3rd group treated with both rutin-supplemented SD (50 mg/kg feed), and DW contain Pb (350 mg/L). Finally, the 4th group administered RCA NPs-supplemented SD (50 mg/kg feed) and Pb-incorporated DW (350 mg/L). On the 40th day of experiment, broilers weighed, and blood samples collected for biochemical and hematological analysis then slaughtered. Economic efficiency, growth performance, and oxidative stress biomarkers were evaluated. Gene expression level of growth-associated genes as insulin-like growth factor-I (IGF-1) and histopathological changes were assessed in liver and intestinal tissue of both breeds. Our results revealed that Pb-treated birds exhibited the lowest average body weight gain (BWG) and economic efficiency measures in both breeds while RCA NPs-treated groups revealed enhanced growth and economic performance. Furthermore, diet supplementation with RCA NPs considerably enhanced the antioxidant enzymes activity and expression of growth-associated genes than groups treated with rutin alone specifically in AR breed. In conclusion, RCA NPs supplementation could be a promising nanoformulation in poultry production through enhancing the antioxidant capacity and bioavailability of rutin.Graphical

An efficient ionic gelation based nano-delivery system to improve the stability and controlled release of saffron extracts

Saffron bioactive compounds possess exceptional nutritional and health properties. However, their industrial utilization has been limited due to challenges such as low solubility, poor bioavailability, untargeted release, and instability during processing and preparation. This study aimed to improve the delivery and stability of nano-sized saffron extracts as a rich antioxidant and anticancer agent via an ionic gelation-based approach. Efficient alcoholic and aqueous extracts of saffron loaded in chitosan-alginate nanoparticles (CANPs) were developed. Size and zeta potential of produced CANPs recorded in the range of 218–251 nm and 27.5–53.6 mV, respectively. The spherical CANPs showed high encapsulation efficiency. Also, AFM analysis depicted the distinct shape and uniform size distribution of prepared CANPs. The CANPs swelled in neutral solution, while in acidic conditions, it tended to shrink. The release profiles revealed that non-Fickian diffusion of encapsulants would be controlled by adjusting the pH. The encapsulation of saffron extracts within the CANPs significantly enhanced the storage stability. Both refrigerator and room temperatures in dark condition were detected suitable for the storage of saffron extracts loaded CANPs. Cytotoxicity test against MCF-7 cells demonstrated higher anticancer activity of the aqueous extract compared to the alcoholic extract loaded CANPs. Deionized water demonstrated more efficient performance for saffron extract preparation and biological functions in comparison to ethanolic extract. In brief, the CANPs could be introduced as an efficient protective delivery system for the rich bioactive compounds source, namely saffron extracts in functional food and pharmaceutical industries.

Potential analgesic effect of Foshousan oil-loaded chitosan-alginate nanoparticles on the treatment of migraine.

Background: Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine. Methods: FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug. Results: FSSO-loaded CS-AL NPs (212.1 ± 5.2nm, 45.1 ± 6.2mV) had a well-defined spherical shape with prolonged drug release and good storage within 4weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15μg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104mg/kg) group. Conclusion: FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine.

A Bifunctional Chitosan/Alginate Nanoparticles (CANPs) for Trace Metals Adsorption as well as Antibacterial Polyelectrolyte Complex (PEC) Materials

Chitosan/Alginate Nanoparticles (CANPs) were produced via microemulsion method. SEM images captured that CANPs has rough, irregular, and porous surfaces. The particle sizes were in the range of 1-15 nm with an average diameter of 8.31 nm. CANPs were applied for trace metals removal. Optimum adsorption capacity of Zn(II) and Cu(II) were 8.144 and 5.582 mg g-1, respectively. Kinetic studies show that the adsorption of Zn(II) and Cu(II) onto CANPs fitted pseudo second order model. Isotherm studies determined that the sorption followed Dubinin-radushkevich model. Zn(II) adsorbed CANPs (Zn/CANPs) and Cu(II) adsorbed CANPs (Cu/CANPs) were investigate their antibacterial activity againts E. coli and S. aureus. Zone of Inhibition (ZOI) of Zn/CANPs were 19.3 mm (E. coli) and 17.5 mm (S. aureus). ZOI of Cu/CANPs were 14.17 mm (E. coli) and 10.75 mm (S. aureus). The results revealed that CANPs were a promising bifunctional material for metals removal and has good antibacterial activity.

Reproductive Performance of Female Rabbits Inseminated with Extenders Supplemented with GnRH Analogue Entrapped in Chitosan-Based Nanoparticles.

Rabbit is a reflexively ovulating species. Accordingly, in the practice of artificial insemination (AI) ovulation must be induced via exogenous GnRH (Gonadotropin-Releasing Hormone) administration, which may be performed intramuscularly, subcutaneously, or intravaginally. Unfortunately, the bioavailability of the GnRH analogue when added to the extender is lower due to the proteolytic activity in the seminal plasma and the poor permeability of the vaginal mucosa. The aim of the study was to refine the practice of AI practice in rabbits by replacing parenteral GnRH analogue administration (subcutaneous, intravenous, or intramuscular injection) with intravaginal application, while reducing its concentration in the diluent. Extenders containing the buserelin acetate in chitosan-dextran sulphate and chitosan-alginate nanoparticles were designed and 356 females were inseminated. Reproductive performance of females inseminated with the two experimental extenders, receiving 4 μg of buserelin acetate intravaginally per doe, was compared with that in the control group, the does of which were inseminated with the extender without the GnRH analogue and induced to ovulate with 1 μg of buserelin acetate administered intramuscularly. The entrapment efficiency of the chitosan-dextran sulphate complex was higher than that of chitosan-alginate. However, females inseminated with both systems showed similar reproductive performance. We conclude that both nanoencapsulation systems are an efficient way of intravaginal ovulation induction, allowing a reduction in the level of the GnRH analogue normally used in seminal doses from 15-25 μg to 4 μg.

Synthesis and evaluation of modified lens using plasma treatment containing timolol-maleate loaded lauric acid-decorated chitosan-alginate nanoparticles for glaucoma

Reducing intraocular pressure (IOP) with eye drops is one of the most common ways to control glaucoma. Low bioavailability and high frequency of administration in eye drops are major challenges in ocular pharmacotherapy. Contact lenses have attracted the attention of scientists in recent decades as an alternative method. In this study, with the aim of long-term drug delivery and better patient compatibility, contact lenses with surface modification and nanoparticles were used. In this study, timolol-maleate was loaded into polymeric nanoparticles made of chitosan conjugate with lauric acid and sodium alginate. Then silicon matrix was mixed with a curing agent (10:1), and the suspension of nanoparticles was added to the precursor and cured. Finally, for surface modification, the lenses were irradiated with oxygen plasma at different exposure times (30, 60, and 150 s) and soaked in different BSA concentrations (1, 3, and 5% w/v). The results showed nanoparticles with a size of 50 nm and a spherical shape were synthesized. The best surface modification of the lenses was for 5 (% w/v) albumin concentration and 150 s exposure time, which had the highest increase in hydrophilicity. Drug release from nanoparticles continued for 3 days and this amount increased to 6 days after dispersion in the modified lens matrix. The drug model and kinetic study show the Higuchi model completely supported the release profile. This study represents the novel drug delivery system to control intra-ocular pressure as a candidate platform for glaucoma treatment. Improved compatibility and drug release from the designed contact lenses would prepare new insight into the mentioned disease treatment.

Amoxicillin-docosahexaenoic acid encapsulated chitosan-alginate nanoparticles as a delivery system with enhanced biocidal activities against Helicobacter pylori and improved ulcer healing.

Encapsulation of amoxicillin (AMX) for drug delivery against Helicobacter pylori infection and aspirin-induced ulcers in rat's stomachs was performed using docosahexaenoic acid (DHA)-loaded chitosan/alginate (CA) nanoparticles (NPs) developed by ionotropic gelation method. The physicochemical analyses of the composite NPs were performed by scanning electron microscopy, Fourier transform infrared spectroscopy, zeta potential, X-ray diffraction, and atomic force microscopy. The encapsulation efficiency of AMX was increased to 76% by incorporating DHA, which resulted in a reduction in the particle size. The formed CA-DHA-AMX NPs effectively adhered to the bacteria and rat gastric mucosa. Their antibacterial properties were more potent than those of the single AMX and CA-DHA NPs as demonstrated by the in vivo assay. The composite NPs attained higher mucoadhesive potential during food intake than during fasting (p = 0.029). At 10 and 20 mg/kg AMX, the CA-AMX-DHA showed more potent activities against H. pylori than the CA-AMX, CA-DHA, and single AMX. The in vivo study showed that the effective dose of AMX was lower when DHA was included, indicating better drug delivery and stability of the encapsulated AMX. Both mucosal thickening and ulcer index were significantly higher in the groups receiving CA-DHA-AMX than in the groups receiving CA-AMX and single AMX. The presence of DHA declines the pro-inflammatory cytokines including IL-1β, IL-6, and IL-17A. The synergistic effects of AMX and the CA-DHA formulation increased the biocidal activities against H. pylori infection and improved ulcer healing properties.

Advantageous Combinations of Nanoencapsulated Oregano Oil with Selected Antibiotics for Skin Treatment.

The aim of the present study was to evaluate the antimicrobial activity of combinations between encapsulated oregano oil and the most commonly applied antibiotics (ciprofloxacin or gentamicin) against skin infections. In particular, chitosan-alginate nanoparticles loaded with oregano oil and the selected antibiotics were included in methylcellulose hydrogels. Consistency, spreadability, pH of the hydrogel and in vitro release rate of the oil were considered appropriate for topical application. The combination of encapsulated oil and gentamicin in the hydrogel resulted in a synergistic effect against methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus strains. It was expressed in a fourfold reduction in the effective concentration of gentamicin and 98% inhibition of the bacterial metabolic activity. When ciprofloxacin was included in the combination instead of gentamicin, an additive effect with a two-fold decrease in the effective drug concentration and a 96% reduction in the bacterial metabolic activity were observed. Both combinations significantly inhibited the formation of MRSA biofilm by more than 90% when applied. In vivo application of the hydrogel containing the synergistic combination between the encapsulated oil and gentamicin did not induce irritation of the rabbit skin.

Enhanced Nasal Deposition and Anti-Coronavirus Effect of Favipiravir-Loaded Mucoadhesive Chitosan-Alginate Nanoparticles.

Favipiravir (FVR) is a repurposed antiviral drug for treating mild to moderate cases of the novel coronavirus disease 2019 (COVID-19). However, its poor solubility and permeability limit its clinical efficacy. To overcome its physicochemical and pharmacokinetic limitations, we statistically designed a mucoadhesive chitosan-alginate nanoparticles (MCS-ALG-NPs) as a new carrier for FVR using response surface methodology, which provided suitable characteristics for transmucosal delivery. The use of mucoadhesive polymers for intranasal administration promotes the residence time and contact of FVR in the mucus membrane. The optimized FVR-MCS-ALG-NPs demonstrated superior mucoadhesion, higher permeation and deposition in the nasal mucosa, and a significant increase in the inhibition of viral replication over 35-fold compared with free FVR. The overall results suggest that MCS-ALG-NPs could be used as an effective mucoadhesive carrier to enhance the activity of FVR against COVID-19.

RETRACTED: Chitosan-alginate nanoparticles of cabazitaxel: Design, dual-receptor targeting and efficacy in lung cancer model

Cabazitaxel (CZT) loaded chitosan-alginate based (CSA) nanoparticles were developed with dual targeting functions of both folate receptor and epidermal growth factor receptor (EGFR) using ionic gelation technique. The chitosan-folate conjugate was synthesized, and characterized by using FTIR, NMR and Mass spectroscopy. The physicochemical parameters and morphology of all CSA nanoparticles were examined. The degree of conjugation of folic acid and cetuximab (CTXmab) was determined by UV–Visible spectroscopy and Bradford assay, respectively. Moreover, XPS analysis also supported the presence of the ligands on nanoparticles. The cellular-uptake study performed on A-549 cells demonstrated a significant enhancement in the uptake of dual-receptor targeted CSA nanoparticles than non-targeted and single-receptor targeted CSA nanoparticles. Further, CZT-loaded dual receptors targeted CSA nanoparticles also showed significantly lower IC50 values (~38 folds) than the CZT control against A-549 cells. Further, in-vivo histopathological evaluations of dual receptor-targeted CSA nanoparticles have demonstrated better safety in Wistar rats. Moreover, its treatment on the Benzo(a)pyrene (B(a)P) induced lung cancer mice model has showed the enhanced anticancer efficacy of CZT with a prolonged survival rate.

Lauric acid-grafted biopolymeric nanoparticles for efficient Melphalan delivery across the corneal layers for retinoblastoma: ex vivo and in vivo permeation study

Intravitreal injection of chemotherapy drugs for intraocular retinoblastoma, for the prevalent pediatric malignancy treatment with the side effects of severe infection. This study tried to synthesize the novel approach to deliver Melphalan to the vitreous cavity through the cornea to increase drug efficacy with non-invasive effects. For this purpose, lauric acid-grafted chitosan-alginate and chitosan-alginate loaded by Melphalan nanoparticles were fabricated. Fourier-transform infrared spectroscopy (FTIR) and x-ray diffraction (XRD) were the basic characterizations of chitosan modification. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) are the other assessments of synthesized nanoparticles. Drug encapsulation and in vitro release were studied using UV-spectroscopy, also ex vivo and in vivo corneal permeation was studied using Franz diffusion cell, fluorescence microscopy, and in vivo animal imaging. FTIR and XRD confirm the successful grafting of lauric acid and spherical shape with the average size of 50 nm and 80 nm observed for modified and chitosan-alginate nanoparticles respectively. In the release study, encapsulation efficiency of 98% with sustained drug release of 80% for 100 h with the Fickian drug diffusion mechanism was reported. Ex vivo corneal permeation exhibited an improved drug penetration rate in the sample of lauric acid-grafted-chitosan-alginate nanoparticles with the results of 5.8 times higher than chitosan-alginate nano-carriers and 15.5-fold compared to drug solution. Also, in vivo study shows that the designed nanoparticles containing Melphalan reached the vitreous cavity with high efficacy. Current investigations illustrate the novel Melphalan delivery with sustained behavior through the cornea with the high potential of corneal layer penetration for retinoblastoma management.

Empagliflozin containing chitosan-alginate nanoparticles in orodispersible film: preparation, characterization, pharmacokinetic evaluation and its in-vitro anticancer activity

Objective The main objective of this study was to develop the orodispersity film containing chitosan-alginate nanoparticles to improve dissolution profile, therapeutic effect with improved bioavailability of empagliflozin through oral route noninvasively for further cytotoxicity study. Methods The nanoparticles were developed through two-step mechanisms ionotropic pre-gelation and polyelectrolyte complexation methods. The prepared nanoparticles were added to a polymer matrix containing hypromellose, polyvinyl alcohol, and maltodextrin and cast to rapidly dissolving thin film by solvent casting method. Results The physicochemical characteristics of empagliflozin in the orodispersible film were most favorable for further studies. This formulation has achieved a higher permeability (7.2-fold) as compared to the reference drug product (Jardiance) after 45 min. In vivo pharmacokinetic studies in Wistar rats have revealed that chitosan-alginate empagliflozin nanoparticles in the orodispersible film were 1.18-fold more bioavailable in comparison to free empagliflozin in orodispersible film. The C max observed for the empagliflozin-loaded orodispersible film was 15.42 ± 5.13 μg/mL in comparison to 18.21 ± 5.53 μg/mL for empagliflozin nanoparticle-containing orodispersible film and 12.19 ± 6.71 μg/mL for freed rug suspension. The t1/2and AUC0-t values for chitosan-alginate nanoparticles of empagliflozin in the orodispersible film were found1.4-fold more than empagliflozin loaded orodispersible film (without nanoparticles). The cytotoxicity study has shown that chitosan-alginate nanoparticles of empagliflozin in orodispersible film achieved a 2.5-fold higher cytotoxic effect than free empagliflozin in orodispersible film in A549lung cancer cells. Conclusions This study provides evidence that chitosan-alginate nanoparticles of empagliflozin in orodispersible film can be an effective drug carrier system to improve sustained effect with better bioavailability of poorly water-soluble drug.

Phenytoin-loaded bioactive nanoparticles for the treatment of diabetic pressure ulcers: formulation and in vitro/in vivo evaluation

Drug repurposing offers the chance to explore the full potential of existing drugs while reducing drug development time and costs. For instance, the anticonvulsant drug phenytoin (PHT) has been investigated for its wound healing properties. However, its poor solubility and variability of doses used topically limit its use. Hence, the aim of this study was to improve the properties and wound healing efficacy of PHT for the treatment of diabetic bedsores. PHT was encapsulated, using a modified ionic gelation method, in either positively or negatively charged chitosan-alginate nanoparticles (NPs), which possess previously demonstrated wound healing potential. These NPs were characterized by transmission electron microscopy, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. PHT-loaded NPs were evaluated in vivo for their pressure ulcers’ healing potential using diabetic rats. The prepared NPs, especially the positively charged particles, exhibited superior wound healing efficacy compared to PHT suspension, with respect to healing rates, granulation tissue formation, tissue maturation, and collagen content. The positively charged NPs resulted in a 56.54% wound closure at day 7, compared to 37% for PHT suspension. Moreover, skin treated with these NPs showed a mature dermis structure with skin appendages, which were absent in all other groups, in addition to the highest collagen content of 63.65%. In conclusion, the use of a bioactive carrier enhanced the healing properties of PHT and allowed the use of relatively low doses of the drug. Our findings suggest that the prepared NPs offer an effective antibiotic-free delivery system for diabetic wound healing applications.Graphical

Application of chitosan/alginate nanoparticle in oral drug delivery systems: prospects and challenges

Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g. ulcerative colitis and colorectal cancer), as they improve therapeutic efficiency and reduce systemic toxicity. Chitosan/alginate nanoparticles (CANPs) show strong electrostatic interaction between the carboxyl group of alginates and the amino group of chitosan which leads to shrinkage and gel formation at low pH, thereby protecting the drugs from the gastrointestinal tract (GIT) and aggressive gastric environment. Meanwhile, CANPs as biocompatible polymer, show intestinal mucosal adhesion, which could extend the retention time of drugs on inflammatory sites. Recently, CANPs have attracted increasing interest as colon-targeted oral drug delivery system for intestinal diseases. The purpose of this review is to summarize the application and treatment of CANPs in intestinal diseases and insulin delivery. And then provide a future perspective of the potential and development direction of CANPs as colon-targeted ODDSs.

Preparation and Characterization of Blank and Nerolidol-Loaded Chitosan-Alginate Nanoparticles.

Recently, there has been a growing interest in using natural products as treatment alternatives in several diseases. Nerolidol is a natural product which has been shown to have protective effects in several conditions. The low water solubility of nerolidol and many other natural products limits their delivery to the body. In this research, a drug delivery system composed of alginate and chitosan was fabricated and loaded with nerolidol to enhance its water solubility. The chitosan–alginate nanoparticles were fabricated using a new method including the tween 80 pre-gelation, followed by poly-ionic crosslinking between chitosan negative and alginate positive groups. Several characterization techniques were used to validate the fabricated nanoparticles. The molecular interactions between the chitosan, alginate, and nerolidol molecules were confirmed using the Fourier transform infrared spectroscopy. The ultraviolet spectroscopy showed an absorbance peak of the blank nanoparticles at 200 nm and for the pure nerolidol at 280 nm. Using both scanning and transmission electron microscopy, the nanoparticles were found to be spherical in shape with an average size of 12 nm and 35 nm for the blank chitosan–alginate nanoparticles and the nerolidol-loaded chitosan–alginate nanoparticles, respectively. The nanoparticles were also shown to have a loading capacity of 51.7% and an encapsulation efficiency of 87%. A controlled release profile of the loaded drug for up to 28 h using an in vitro model was also observed, which is more efficient than the free form of nerolidol. In conclusion, chitosan–alginate nanoparticles and nerolidol loaded chitosan–alginate nanoparticles were successfully fabricated and characterized to show potential encapsulation and delivery using an in vitro model.