Ionotropic Gelation Method Research Articles

Antioxidant properties and effects of formulation variables on <i>Ceiba pentandra</i> microspheres

Background: New drug delivery techniques have improved therapeutic and physicochemical properties of herbal medicines.Objective: Extracts of Ceiba pentandra (CP) leaf have been evaluated for antioxidant properties with the aim of formulating them into microspheres and studying release of flavonoid from the dosage form.Materials and Methods: Microspheres were prepared from extracts of CP using ionotropic gelation method. Formulation parameters were varied to produce A1 to A8. Microspheres were evaluated for size, shape, yield, micrometrics, swelling, entrapment efficiency, and flavonoid release characteristics. Factorial experimentation design was used to determine the individual and interactive effects of the formulation variables on entrapment efficiency and flavonoid release. Results were analysed using ANOVA at p≤0.05.Results: The extract contained flavonoids. Microspheres were discrete, porous, spherical, with good flow. Microspheres swelled moderately and eroded within 3 hours. Entrapment efficiencies ranged from 4.17 to 19.2 %. All Formulations released 80 % of flavonoid within 6 hours, except A2, A3 and A8 which sustained flavonoid release for 24 – 26 hours. Concentration of polymer had the highest positive effect, while stirring speed had the highest negative effect on microsphere entrapment efficiency. Effect of curing time on entrapment efficiency was positive but insignificant. Polymer concentration and curing time had negative effects on flavonoid release, while stirring speed showed a positive effect.Conclusion: Extracts of Ceiba pentandra leaves possess antioxidant constituents and could be formulated into microspheres of good physicochemical properties. Concentrations of polymer and curing time are important parameters that should be considered in the formulation of CP into microspheres with sustained release potentials.

Chitosan/starch based unoxidized tannic acid modified microparticles for rapid hemostasis with broad spectrum antibacterial activity

The development of a rapid hemostat through a facile method with co-existing antibacterial activity and minimum erythrocyte lysis property stands as a major requirement in the field of hemostasis. Herein, a series of novel microparticle hemostats were synthesized using chitosan, different hydrothermally-treated starches, and cross-linked with tannic acid (TA) simultaneously in an unoxidized environment via ionotropic gelation method. Hemostats' comparative functional properties, such as adjustable antibacterial and erythrocyte compatibility upon various starch additions were evaluated. The in vivo hemostatic study revealed that the developed hemostats for mouse liver laceration and rat tail amputation had clotting times (13 s and 38 s, respectively) and blood loss (51 mg and 62 mg, respectively) similar to those of Celox™. The erythrocyte adhesion test suggested that erythrocyte distortion can be lowered by modifying the antibacterial hemostats with different starches. The broad-spectrum antibacterial efficacy of the hemostats remained intact against S. aureus (>90 %), E. coli (>80 %), and P. mirabilis bacteria upon starch modification. They also demonstrated high hemocompatibility (<3 % hemolysis ratio), moderate cell viability (>81 %), in vivo biodegradation, and angiogenesis indicating adequate biocompatibility and wound healing. The developed hemostats hold significant promise to be employed as rapid hemostatic agents for preventing major bleeding and bacterial infection in emergencies.

Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Echis carinatus Venom.

Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc.). Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects. In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay. The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells. It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.

Synthesis, Characterization and Drug Release Study of Novel Guided Tissue Regeneration Membranes Containing Drug Loaded Chitosan Nanoparticles

Periodontitis is an inflammatory disease which can cause the destruction of the supporting tissues of the tooth leading to tooth loss. The guided tissue regeneration is considered as a gold standard for its treatment but the re-infection of surgical site limits its overall success. Objective: To synthesize novel monolayer guided tissue regeneration (GTR) membrane containing drug loaded chitosan nanoparticles and to evaluate the drug release from the synthesized GTR membranes. Methods: The chitosan nanoparticles containing ciprofloxacin were synthesized by the ionotropic gelation method and these synthesized nanoparticles were added into chitosan GTR membrane fabricated by the freeze gelation method. For comparison GTR membrane was prepared as a control by freeze gelation method in which the drug was added directly. The prepared membranes were characterized by the SEM and FTIR. The drug release was measured from the membrane samples in the phosphate buffer saline (PBS) at 1, 3, 5, 7 and 9 days. Results: The GTR membrane containing the ciprofloxacin loaded chitosan nanoparticles showed fast drug release as compared to the membrane in which the ciprofloxacin was added directly. Conclusions: The inclusion of antibiotic loaded chitosan nanoparticles can increase the drug release from GTR membrane.

Synthesis of BLF1-containing trimethyl chitosan nanoparticles and evaluation of its immunogenicity and protection in syrian mice by oral and subcutaneous injections

The bacterium Burkholderia pseudomallei is the cause of melioidosis infectious disease. In this bacterium, the BLF1 protein wide inhibits the synthesis of proteins in human cells. This disease is reported to cause a death rate of 40% in some parts of the world. Currently, no effective vaccine is available against this bacterial infection. In this study, therefore, a Nano vaccine was synthesized based on the trimethyl chitosan (TMC) polymer containing the BLF1 recombinant protein, and its immunogenicity and protection in Syrian mice were evaluated by oral and subcutaneous injections. The BLF1 recombinant protein expression was induced in Escherichia coli Bl21 (DE3) and purified by the affinity chromatography technique. Recombinant protein-containing nanoparticles (NPs) were then synthesized by the ionotropic gelation method. After oral and subcutaneous injections, antibody titration was assessed by the indirect ELISA assay. Finally, murine groups were challenged using the BLF1 toxin. The results indicated that the immune system showed more antibody titration in subcutaneous injection than in the oral form. However, the results were reversed in the challenge results, and the survival rate was more significant in the oral injection.

Bee chitosan nanoparticles loaded with apitoxin as a novel approach to eradication of common human bacterial, fungal pathogens and treating cancer.

Antimicrobial resistance is one of the largest medical challenges because of the rising frequency of opportunistic human microbial infections across the globe. This study aimed to extract chitosan from the exoskeletons of dead bees and load it with bee venom (commercially available as Apitoxin [Api]). Then, the ionotropic gelation method would be used to form nanoparticles that could be a novel drug-delivery system that might eradicate eight common human pathogens (i.e., two fungal and six bacteria strains). It might also be used to treat the human colon cancer cell line (Caco2 ATCC ATP-37) and human liver cancer cell line (HepG2ATCC HB-8065) cancer cell lines. The x-ray diffraction (XRD), Fourier transform infrared (FTIR), and dynamic light scattering (DLS) properties, ζ-potentials, and surface appearances of the nanoparticles were evaluated by transmission electron microscopy (TEM). FTIR and XRD validated that the Api was successfully encapsulated in the chitosan nanoparticles (ChB NPs). According to the TEM, the ChB NPs and the ChB NPs loaded with Apitoxin (Api@ChB NPs) had a spherical shape and uniform size distribution, with non-aggregation, for an average size of approximately 182 and 274 ± 3.8 nm, respectively, and their Zeta potential values were 37.8 ± 1.2 mV and - 10.9 mV, respectively. The Api@ChB NPs had the greatest inhibitory effect against all tested strains compared with the ChB NPs and Api alone. The minimum inhibitory concentrations (MICs) of the Api, ChB NPs, and Api@ChB NPs were evaluated against the offer mentioned colony forming units (CFU/mL), and their lowest MIC values were 30, 25, and 12.5 μg mL-1, respectively, against Enterococcus faecalis. Identifiable morphological features of apoptosis were observed by 3 T3 Phototox software after Api@ChB NPs had been used to treat the normal Vero ATCC CCL-81, Caco2 ATCC ATP-37, and HepG2 ATCC HB-8065 cancer cell lines for 24 h. The morphological changes were clear in a concentration-dependent manner, and the ability of the cells was 250 to 500 μg mL-1. These results revealed that Api@ChB NPs may be a promising natural nanotreatment for common human pathogens.

Optimization of Malabar Nut (Justicia adhatoda L.) Leaves’ Phenolic Compounds by Alginate Emulsion-gelation Approach using Response Surface Methodology

Background: The encapsulation technique is an effective method for coating bioactive molecules and protecting them against various technological treatment conditions during production processing. Objective: The aim of this study was to optimize the encapsulation conditions of phenolic compounds extracted from Malabar nut (Justicia adhatoda L.) leaves by alginate emulsion-gelation approach using response surface methodology Methods: The ionotropic gelation method was used to encapsulate the phenolic compounds of Malabar nut (Justicia adhatoda L.) leaves. The optimization of this phenolic compounds encapsulation was carried out using response surface methodology through Box˗Behnken design. Four parameters with three levels (-1, 0, +1) were chosen including sodium alginate concentration (2 – 3 - 4%), calcium chloride concentration (4 - 6 - 8%), plant extract-alginate solution ratio (0.02 – 0.11 - 0.2 mg/ml), and gelation time (5 – 12.5 - 20 min). of the total phenolic and flavonoid contents encapsulation efficiency was assessed. Likewise, the antioxidant activity was evaluated using ferric-reducing power (FRP) and free radical scavenging activity (DPPH). Results: The results of response surface methodology analysis using Box˗Behnken design showed that the optimal encapsulation conditions were 3.11% for alginate concentration, 5.74% for calcium chloride concentration, 0.1 mg/ml for the plant extract-alginate solution ratio, and 10.80 min for gelation time. Under these conditions, the optimum values of total phenolic and flavonoid encapsulation efficiency were 86.17% and 75.69%, respectively, 126.75 mg AAE/100 g for ferric reducing power and 97.29% for DPPH. The experimental and prediction results have expressed a high significant level for all responses. Conclusion: The method revealed the validity of elaborated models through response surface methodology optimization processes for phenolic antioxidants encapsulation of Malabar nut (Justicia adhatoda L.) leaves extract.

Formulation and evaluation of mucoadhesive microspheres of metronidazole

Objective: Develop and evaluate mucoadhesive microspheres using Chitosan, Sodium alginate, and Sodium carboxymethyl cellulose (NaCMC) for sustained oral delivery of Metronidazole, aiming to improve bioavailability. Methods: Metronidazole-loaded microspheres were prepared via ionotropic gelation method with varying polymer ratios. Particle size, entrapment efficiency, swelling index, mucoadhesion (sheep mucosae), morphology (SEM), in-vitro wash-off test, drug release profile, and stability (6 months) were evaluated. Results: Chitosan content positively correlated with microsphere size. Entrapment efficiency ranged from 51.43% to 94.15%. Chitosan-based formulations, especially MTZ-7 (Chitosan:NaCMC, 3:1), displayed the highest mucoadhesion. SEM analysis revealed rough, spherical microspheres with a continuous polymeric coat. In-vitro wash-off test demonstrated prolonged residence time for Chitosan formulations. Sustained drug release was observed throughout the study, with MTZ-7 exhibiting the most desirable release profile. Stability studies showed no significant changes in drug release for selected formulations after 6 months. Conclusions: Chitosan-based microspheres, particularly MTZ-7, demonstrated superior mucoadhesive properties, sustained and controlled drug release, and desirable stability. These findings suggest the potential of Chitosan-based microspheres as a promising oral drug delivery system for Metronidazole, potentially addressing bioavailability concerns and improving therapeutic efficacy.

A review on micro beads: Formulation, technological aspects, and extraction

Any drug delivery system's purpose is to deliver a therapeutic amount of medicine to the appropriate place in the body while also achieving and maintaining the correct drug concentration. This could be accomplished by using numerous unit dosage forms such as microgranules/spheroids, pellets, microcapsules, and beads, which are divided into many separate units, referred to as subunits, each of which possesses certain desired features. The advantages of micro particle drug delivery systems over single unit dose form are well documented. One of the solutions that does not entail the use of harsh chemicals or elevated temperatures is the production of microbeads medication delivery systems. The traditional procedures require the use of ionotropic gelation methods, which include internal and external gelation methods, emulsion gelation methods, polyelectrolyte complexation methods, and so on. Because of the ease of preparation, the majority of work has been done on the preparation of microbeads using the ionotropic gelation process rather than alternative approaches.

Conception of pH-sensitive calcium alginate/poly vinyl alcohol hydrogel beads for controlled oral curcumin delivery systems. Antibacterial and antioxidant properties

Curcumin, a bioactive compound derived from the rhizome of Curcuma longa, has gained widespread attention for its potential therapeutic properties, including anti-inflammatory, antioxidant and anticancer effects. However, its poor aqueous solubility, instability and limited bioavailability have hindered its clinical applications.New beads formulations based on sodium alginate biopolymer (SA) and poly vinyl alcohol (PVA) were successfully prepared and evaluated as a potential drug vehicle for extended release of curcumin (Cur). Pristine and curcumin loaded calcium alginate/poly vinyl alcohol beads (CA/PVA and CA/PVA/Cur) at different compositions of SA and PVA were prepared by an ionotropic gelation method of SA followed by two freeze-thawing (FT) cycles for further crosslinking of PVA. Characterization techniques, such as scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), UV–Visible spectroscopy, thermogravimetric analysis (TGA) and x-ray diffraction (XRD) were used to confirm the successful microencapsulation of curcumin within the CA/PVA microcapsules. Furthermore, the swelling of pristine beads, pH-sensitive properties and in vitro release studies of curcumin loaded beads were investigated at 37 °C in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF). The effect of the polymer blend ratio, the encapsulation efficiency (EE %) of curcumin, the loading capacity (LC μg/mg), the sphericity factor (SF), the antioxidant activity of the elaborated beads and their antimicrobial properties against bacteria and fungi were just as much evaluated.The obtained results indicate that the swelling and the behavior of the developed beads were influenced by the pH of the test medium and the PVA content. The introduction of PVA into the SA matrix greatly enhanced the physicochemical properties, the encapsulation efficiency and the loading capacity of the elaborated microparticles. Results also suggested that the antioxidant activity of the loaded beads (CA/PVA/Cur) showed a higher DPPH radical scavenging activity while the bacterial and fungal strains proved sensitive to the different formulations used in the assay. Moreover, the important drug encapsulation efficiency and the sustainable drug release of these materials make them promising for the development of new drug carrier systems for colon targeting.

Development of chitosan/carrageenan macrobeads for encapsulation of Paenibacillus polymyxa and its biocontrol efficiency against clubroot disease in Brassica crops

Clubroot, caused by the obligate parasite Plasmodiophora brassicae, is one of the most important diseases of brassicas. The antagonistic bacterium Paenibacillus polymyxa ZF129 can suppress clubroot while its effectiveness is often unstable. To control clubroot more effectively, the macrobeads for controlled release of ZF129 were prepared using microencapsulation technology. Macrobeads with various ratios of chitosan (2 % w/w): carrageenan (0.3 % w/v) were prepared by an ionotropic gelation method and the bacteria ZF129 was loaded into macrobeads. The 1:1 chitosan: carrageenan showed the maximum swelling ratio (634 %), and the maximum survival rate (61.52 ± 1.12 %) after freeze-drying. Fourier transform infrared revealed the electrostatic interactions between chitosan and carrageenan. The macrobeads can efficiently release ZF129 strains into phosphate buffer solution and reach equilibrium in 48 h. The maximum number of bacteria cells to be released in the soil was observed after 25–30 days. The control efficacy of ZF129 macrobeads (chitosan: carrageenan, 1:1) and ZF129 culture against clubroot disease was 76.33 ± 3.65 % and 59.76 ± 4.43 % in greenhouse experiments, respectively and the control efficacy was calculated as 60.74 ± 5.00 % for ZF129 macrobeads and 40.94 ± 4.05 % for ZF129 culture under field experiments, respectively. The ZF129 macrobeads had significant growth-promoting effects on pak choi and Chinese cabbage. The encapsulation method described in this study is a prudent approach toward efficient biopesticides utilization with reduced environmental implications.

Effect of ursodiol on alginate/PLL nanoparticles with non-ionic surfactant for gene delivery

Hearing loss is a widespread condition, affecting people from a range of demographics. Gene therapy is an emerging method for the amelioration of this condition. Challenges associated with the delivery of genes to various sites within the ear remain a significant challenge. In the present work, a novel polymer nanoparticle delivery system was developed, incorporating a bile acid excipient. Bile acids have previously been shown to improve drug delivery through their permeation enhancing properties; however, few studies report their use in gene delivery systems. Nanoparticles were developed with sodium alginate and poly-L-lysine through an ionotropic gelation method. Various surfactants including Tween-80 and poly-ethylene glycol 6000 were incorporated to both improve the solubility of the bile acid, ursodiol, and to modify nanoparticle properties. The evaluation of the nanoparticle’s safety profiles was the primary outcome of this study. The secondary aims were to perform genetic studies, such as transfection efficiency. The nanoparticles generated in this study demonstrated formulation-dependent variability in particle size ranging from 30 to 300 nm. Several of the developed formulations demonstrated suitable safety profiles; further, the introduction of bile acid helped to reduce toxicity. Transfection efficiency for all formulations remained low, potentially due to poor plasmid release inside the cell. Poor transfection efficiency is one of the key pitfalls associated with polymer nanoparticles Overall the present study developed nanoparticles with suitable safety profiles but limited efficacy. The use of modified polymers, additional excipients, and cell-targeting peptides are potential methods that may be explored in future studies to help further improve gene delivery.

Synthesis, characterization, and application of honey stabilized inulin nanoparticles as colon targeting drug delivery carrier

Inulin (INU) is a versatile natural polysaccharide primarily derived from chicory roots. INU possesses the unique quality of evading digestion or fermentation in the early stages of the human digestive tract, instead reaching the lower colon directly. Exploiting on this distinctive attribute, INU finds application in the creation of targeted carrier systems for delivering drugs tailored to colon-related diseases. This study presents a novel method for synthesizing highly stable and non-aggregatory inulin nanoparticles (INU NPs) by ionotropic gelation method, using calcium chloride as crosslinker and natural honey as a stabilizing agent. Different formulation and process parameters were optimized for the synthesis of monodispersed INU NPs. These INU NPs efficiently encapsulated a hydrophilic drug irinotecan hydrochloride trihydrate (IHT) and drug loaded formulation (IINPs) demonstrated excellent colloidal and storage stabilities. Notably, these IINPs exhibited pH-dependent drug release, suggesting potential for colon-specific drug delivery. Anticancer activity of the NPs was found significantly higher in comparison to IHT through cytotoxicity and apoptosis studies against human colorectal carcinoma cells. Overall, this study revealed that the INU NPs synthesized by ionotropic gelation will be an efficient nanocarrier system for colon-targeted drug delivery due to their exceptional biocompatibility and stability in stomach and upper intestinal conditions.

Adsorption of Metal Ions from Single and Binary Aqueous Systems on Bio-Nanocomposite, Alginate-Clay.

The aim of this work is to characterize and evaluate the retention of Cu2+ and Ni2+ from single and binary systems by alginate-Moroccan clay bio-composite with the utilization of calcium chloride as a cross-linking agent, using the ionotropic gelation method. The bio-nanocomposite was characterized by using a variety of techniques (SEM, EDX, XRD, and pHPZC). The efficiency of the adsorbent was investigated under different experimental conditions by varying parameters such as pH, initial concentration, and contact time. To demonstrate the adsorption kinetics, various kinetic models were tried and assessed, including pseudo-first-order, pseudo-second-order, intraparticle diffusion, and Elovich models. The research results show that the adsorption process of Cu2+ and Ni2+ metal ions follows a pseudo-second-order kinetic model, and the corresponding rate constants were identified. To evaluate the parameters related to the adsorption process in both single and binary systems, different mathematical models of isotherms, such as Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich, were investigated. The correlation coefficients obtained showed that the most suitable isotherm for describing this adsorption process is the Langmuir model. The process is considered to be physical and endothermic, as suggested by the positive values of ΔH° and ΔS°, indicating increased randomness at the solid/liquid interface during Cu2+ and Ni2+ adsorption. Furthermore, the spontaneity of the process is confirmed by the negative values of ∆G°. The bio-nanocomposite beads demonstrated a maximum adsorption capacity of 370.37 mg/g for Ni2+ and 454.54 mg/g for Cu2+ in the single system. In the binary system, the maximum adsorption capacities were observed to be 357.14 mg/g for Ni2+ and 370.37 mg/g for Cu2+. There is significant evidence for the use of alginate-Moroccan clay bio-nanocomposite as a cost-effective alternative adsorbent for the efficient removal of metal ions in single and binary systems.

Zn/Al layered double hydroxide and carboxymethyl cellulose composite beads as support for the catalytic gold nanoparticles and their applications in the reduction of nitroarenes

Until now, many efficient catalysts have been reported that are used for the reduction of nitroarenes. However, a catalyst reusability is a challenge that is often faced in practical environment. In this report, we designed a hydrogel composite (CMC-LDH), which act as support and making it possible to address this challenge. In this research work, zinc/aluminum based layered double hydroxides (Zn/Al LDH) have been assembled with carboxymethyl cellulose (CMC) to prepare CMC/LDH hydrogel beads. The CMC/LDH hydrogel beads were prepared by the ionotropic gelation method. For CMC/LDH/Au preparation, the already prepared CMC/LDH beads were kept in gold ion (Au3+) solution, and their subsequent reduction with sodium borohydride (NaBH4). For the characterization of the prepared samples different instrumental techniques, such as Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy, and scanning electron microscopy (SEM) were adopted. For the catalytic evaluation of CMC/LDH/Au, it was utilized as a catalyst in 4-NP and 4-NA reduction reactions. The continuity of the reaction was monitored by a UV–visible spectrophotometer. Rate constant (kapp) of 0.48474 min−1 and 0.7486 min−1 were obtained for 4-NP and 4-NA reduction, respectively. The hydrogel beads were recycled and reused for up to five successive cycles without significantly changing their catalytic efficiency.

Non-invasive peptides delivery using chitosan nanoparticles assembled via scalable microfluidic technology

The delivery of peptides via non-invasive administration routes remains a challenge to be addressed. In this regard, chitosan nanoparticles (CS NPs) have shown promise. However, their current batch preparation methods (ionotropic gelation, polyelectrolyte complexing, emulsification solvent diffusion or micro emulsification) have proven difficult to scale up. Here, we established a microfluidic-assisted ionotropic gelation method for the manufacturing of CS NPs, ionically crosslinked with sodium tripolyphosphate (TPP), and loaded with a model peptide, Argireline. The microfluidic process was optimized through a design of experiments approach. CS concentration and pH have the greatest effect on particle size, while CS and TPP concentrations and pH on PDI. The optimum formulation was successfully loaded with the peptide (90 % EE) and characterized by a size of 186.0 ± 1.0 nm and a PDI of 0.440 ± 0.002. Subsequently, Argireline-loaded CS-TPP NPs suspension was converted into a gel for a potential topical application, considering the non-toxic, biocompatible, and biodegradable properties of the components used in the formulation. The NPs gel demonstrated appropriate mechanical properties for Argireline transdermal delivery, along with improved control over its release and enhanced skin permeation for up to 48 h, compared to NPs suspension and free drug solution. Hence, this study demonstrated that the microfluidic-assisted ionotropic gelation method could be an easy-scalable platform for the manufacturing of peptide-loaded CS-TPP NPs which could be potentially applied for the transdermal delivery of biologics.

Preparation and Optimization of Atorvastatin-Loaded Eudragit L100 Polymeric Microbeads by Ionotropic Gelation Method

Preparation and Optimization of Atorvastatin-Loaded Eudragit L100 Polymeric Microbeads by Ionotropic Gelation Method

Vildagliptin loaded polymeric nanoparticles using crosslinked polymer by ionotropic gelation method: development and characterization

Vildagliptin loaded polymeric nanoparticles using crosslinked polymer by ionotropic gelation method: development and characterization

Preparation of novel S-allyl cysteine chitosan based nanoparticles for use in ischemic brain treatment.

Objective: To enhance the brain bioavailability of S-allyl-l-cysteine (SC) by developing novel S-allyl-l-cysteine chitosan nanoparticles (SC CS NPs) and examining the quantity of SC by developing a novel method of ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in ischemic rat brain treatment. Methods: The ionotropic gelation method was used to develop S-allyl cysteine-loaded CS NPs. The 4-factor, 5-level central composite design was optimized to determine the effect of independent variables, i.e., particle size, polydispersity index (PDI), zeta potential, EE, and loading capacity, together with their characterization, followed by drug release and intranasal permeation to enhance the brain bioavailability and examination of their neurobehavioral and biochemical parameters with their histopathological examination. Results: SC CS NPs were optimized at the particle size of 93.21 ± 3.31 nm (PDI: 0.317 ± 0.003), zeta potential of 44.4 ± 2.93, and drug loading of 41.23 ± 1.97% with an entrapment efficiency of 82.61 ± 4.93% having sustain and controlled release (79.92 ± 3.86%) with great permeation (>80.0%) of SC. SC showed the retention time of 1.021 min and 162.50/73.05 m/z. SC showed good linearity in the range of 5.0-1300.0 ng mL-1, % inter-and-intraday accuracy of 96.00-99.06% and CV of 4.38-4.38%. We observed significant results, i.e., p < 0.001 for improved (AUC)0-24 and Cmax delivered via i.v. and i.n. dose. We also observed the highly significantly observations of SC CS NPs (i.n.) based on their treatment results for the biochemical, neurobehavioral, and histopathological examination in the developed ischemic MCAO brain rat model. Conclusion: The excellent significant role of mucoadhesive CS NPs of SC was proven based on the enhancement in the brain bioavailability of SC via i.n. delivery in rats and easy targeting of the brain for ischemic brain treatment followed by an improvement in neuroprotection based on a very small dose of SC.

Biological activity of lyophilized chitosan scaffolds with inclusion of chitosan and zinc oxide nanoparticles.

The constant demand for biocompatible and non-invasive materials for regenerative medicine in accidents and various diseases has driven the development of innovative biomaterials that promote biomedical applications. In this context, using sol-gel and ionotropic gelation methods, zinc oxide nanoparticles (NPs-ZnO) and chitosan nanoparticles (NPs-CS) were synthesized with sizes of 20.0 nm and 11.98 nm, respectively. These nanoparticles were incorporated into chitosan scaffolds through the freeze-drying method, generating a porous morphology with small (<100 μm), medium (100-200 μm), and large (200-450 μm) pore sizes. Moreover, the four formulations showed preliminary bioactivity after hydrolytic degradation, facilitating the formation of a hydroxyapatite (HA) layer on the scaffold surface, as evidenced by the presence of Ca (4%) and P (5.1%) during hydrolytic degradation. The scaffolds exhibited average antibacterial activity of F1 = 92.93%, F2 = 99.90%, F3 = 74.10%, and F4 = 88.72% against four bacterial strains: K. pneumoniae, E. cloacae, S. enterica, and S. aureus. In vivo, evaluation confirmed the biocompatibility of the functionalized scaffolds, where F2 showed accelerated resorption attributed to the NPs-ZnO. At the same time, F3 exhibited controlled degradation with NPs-CS acting as initiation points for degradation. On the other hand, F4 combined NPs-CS and NPs-ZnO, resulting in progressive degradation, reduced inflammation, and an organized extracellular matrix. All the results presented expand the boundaries in tissue engineering and regenerative medicine by highlighting the crucial role of nanoparticles in optimizing scaffold properties.