Alginate-chitosan Nanoparticles Research Articles

Polymeric nanoparticles for oral delivery of biopharmaceuticals: an overview

Biopharmaceuticals, cutting-edge medications sourced from living organisms, embody the zenith of therapeutic progress driven by biotechnological breakthroughs. While oral drug delivery is convenient, it proves challenging for biopharmaceuticals due to the complex barriers in the gastrointestinal tract. Their delicate structure and susceptibility to degradation in the gut pose formidable obstacles. This scientific conundrum necessitates innovative solutions to ensure their effectiveness. Pseudomonas aeruginosa's Exotoxin A demonstrates the difficulty in traversing the intestinal epithelium, necessitating innovative strategies. Researchers utilize mucoadhesive, biodegradable polymers like alginate and chitosan to create nanoparticles. These nanoparticles form a protective gel in the stomach's acidic environment, enhancing drug stability and absorption. Chitosan and alginate collaborate in nanoparticle formulations, improving mucosal adhesion and prolonging drug retention. Introducing non-toxic Exotoxin A enhances trans-epithelial transport, validated by in vitro studies on Caco-2 cell monolayers and accumulation in the rat small intestine's lamina propria. Utilizing green fluorescent protein as a model within alginate-chitosan nanoparticles showcases their potential for oral drug delivery. Bacterial toxins play a crucial role in enhancing trans-epithelial transport, endorsing these nanoparticles. This fusion of biotechnology and polymer science offers a promising solution for biopharmaceutical oral delivery challenges, highlighting alginate-chitosan nanoparticles as versatile carriers for transformative drug delivery advancements.

Potential of asiaticoside encapsulated alginate chitosan nanoparticles in the management of antiproliferative activity in C6 glioma cells

BackgroundAsiaticoside is a pentacyclic triterpenoid saponin constituent of the medicinal herb Centella asiatica, known for its neuroprotective, anticancer and other biological effects. The present study aims to develop and characterise asiaticoside encapsulated alginate chitosan nanoparticles (ACNPs) and evaluate their antiproliferative potential on C6 glioma cells. MethodsACNPs were prepared by the ionic gelation polyelectrolyte complexation technique and characterised by dynamic light scattering, scanning electron microscopy and transmission electron microscopy. Cytotoxicity and antiproliferative effect of ACNPs were studied on C6 glioma cells using MTT and EdU-assays. Apoptosis/necrosis in C6 glioma cells was determined by annexin V and acridine orange/ethidium bromide (AO/EtBr) assays. Intracellular ROS generation in C6 glioma cells exposed with ACNP was determined by DCFDA assay using flow cytometry. Cell cycle analysis in C6 glioma cells treated with ACNP was performed by flow cytometry. ResultsSynthesised ACNPs showed spherical shape with 200 nm particle size, good thermal stability, and an acceptable polydispersity index. ASI from synthesized ACNPs demonstrated 90% encapsulation efficiency (EE) and 10% drug release within 24 h. Upon ACNP treatment mBA cells exhibited good cell viability and intact cell morphology. However, C6 cells displayed dose-dependent cytotoxicity when treated with ACNP. Annexin V and acridine orange/ethidium bromide (AO/EtBr) assays revealed late apoptosis and necrosis (p < 0.05) in C6 glioma cells treated with ACNP. Likewise, ACNPs significantly augmented reactive oxygen species generation (p < 0.05) in C6 glioma cells. ACNP treatment also resulted in cell cycle arrest at the G1 phase with chromatin condensation in C6 glioma cells. ConclusionsThese findings suggest that ACNPs act as an antiproliferative agent against C6 glioma cells via an increased intracellular ROS pathway that promotes apoptosis/necrosis. This study throws light on more in-depth mechanistic aspects of managing brain disorders using C. asiatica and its phytoconstituents.

Glutaraldehyde Crosslinked Alginate-Chitosan Nanoparticles as Paracetamol Adsorbent

Paracetamol contained in wastewater can cause adverse effects on animal ecosystems, such as fish living in waters and cause harmful effects on humans. Adsorption techniques are used to remove these pharmaceutical compounds. Alginate-chitosan nanoparticles are non-toxic and effectively used as adsorbents to remove pharmaceutical compounds in wastewater. Research on glutaraldehyde crosslinked alginate-chitosan nanoparticles as paracetamol adsorbent has been carried out. This research used the ionic gelation method. Nanoparticles were characterized using transmission electron microscopy (TEM), scanning electron microscope (SEM-EDX) and Fourier transform infra-red spectrophotometer (FTIR). Furthermore, the nanoparticles were used for paracetamol adsorption. The results showed that the form nanoparticles are coarse solid powder and brownish yellow. The TEM image shows an average nanoparticle size of 8.22 nm. Glutaraldehyde crosslinked alginate-chitosan nanoparticles adsorbed paracetamol with adsorption kinetics followed a pseudo-second-order or Ho-McKay model, the adsorption rate constant of 0.0324 g mg−1 min−1. The isotherm study of paracetamol adsorption by glutaraldehyde cross-linked alginate-chitosan nanoparticles followed the isotherm Dubinin-Radushkevich isotherm model with a free energy value of 707.1068 kJ mol−1, and this value indicates the adsorption process by chemically or chemisorption.

Revolutionizing goat milk gels: A central composite design approach for synthesizing ascorbic acid-functionalized iron oxide nanoparticles decorated alginate-chitosan nanoparticles fortified smart gels

Goat milk gels (GMGs) are popular food due to their high water content, low-calorie density, appealing taste, texture enhancers, stability, and satiety-enhancing characteristics, making them ideal for achieving food security and zero hunger. The GMGs were optimized using the central composite design matrix of response surface methodology using goat milk powder (35–55 g), whole milk powder (10–25 g), and potato powder (10–15 g) as independent variables. In contrast, complex modulus, flow stress, and forward extrudability were chosen as dependent variables. The maximum value of complex modulus 33670.9 N, good flow stress 7863.6 N, and good extrudability 65.32 N was achieved under optimal conditions. The optimized goat milk gel was fortified with ascorbic acid-coated iron oxide nanoparticle (magnetic nature) decorated alginate-chitosan nanoparticles (AA-MNP@CANPs), making it nutritionally rich in an economically feasible way—the decorated AA-MNP@CANPs characterized for size, shape, crystallinity, surface charge, and optical characteristics. Finally, the optimized fortified smart GMGs were further characterized via Scanning electron microscopy, Rheology, Texture profile analysis, Fourier transforms infrared (FTIR), and X-Ray Diffraction (XRD). The fortified smart GMGs carry more nutritional diversity, targeted iron delivery, and the fundamental sustainability development goal of food security.

Amygdalin: A Review on Its Characteristics, Antioxidant Potential, Gastrointestinal Microbiota Intervention, Anticancer Therapeutic and Mechanisms, Toxicity, and Encapsulation.

Bioactive amygdalin, found in high concentrations in bitter almonds, has been recognized as a symbol of the cyanogenic glycoside chemical organic substance, which was initially developed as a pharmaceutical for treating cancer after being hydrolyzed to hydrogen cyanide (HCN). Regrettably, research has shown that HCN can also damage normal cells, rendering it non-toxic to the human body. Extreme controversy surrounds both in vivo and in vitro studies, making its use risky. This review provides an extensive update on characteristics, antioxidant potential, gastrointestinal microbiota intervention, anticancer therapeutic, mechanisms, toxicity, and encapsulation of amygdalin. Antioxidant, anti-tumor, anti-fibrotic, antiatherosclerosis, anti-inflammatory, immunomodulatory, and analgesic characteristics, and the ability to improve digestive and reproductive systems, neurodegeneration, and cardiac hypertrophy are just some of the benefits of amygdalin. Studies verified the HCN-produced amygdalin to be harmful orally, but only at very high doses. Although intravenous treatment was less effective than the oral method, the oral route has a dose range of 0.6 to 1 g daily. Amygdalin’s toxicity depends heavily on the variety of bacteria in the digestive tract. Unfortunately, there is currently no foolproof method for determining the microbial consortium and providing a safe oral dosage for every patient. Amygdalin encapsulation in alginate-chitosan nanoparticles (ACNPs) is a relatively new area of research. Amygdalin has an enhanced cytotoxic effect on malignant cells, and ACNPs can be employed as an active drug-delivery system to release this compound in a regulated, sustained manner without causing any harm to healthy cells or tissues. In conclusion, a large area of research for a substance that might be the next step in cancer therapy is opened up due to unverified and conflicting data.

In vitro cytocompatibility assessment and antibacterial effects of quercetin encapsulated alginate/chitosan nanoparticle

The present work aims at evaluating the in vitro biocompatibility, antibacterial activity and antioxidant capacity of the fabricated and optimized Alginate/Chitosan nanoparticles (ALG/CSNPs) and quercetin loaded Alginate/Chitosan nanoparticles (Q-ALG/CSNPs) with an improved biological efficacy on the hydrophobic flavonoid.The physicochemical properties were determined by TEM and FTIR analysis. The nanoparticles evaluated for the encapsulation of quercetin exerted % encapsulation efficiency (EE) that varied between 76 and 82.4 % and loading capacity (LC) from 31 to 46.5 %. Potential cytotoxicity of the ALG/CSNPs and Q-ALG/CSNPs upon L929 fibroblast cell line was evaluated by MTT reduction Assay and expressed as % cell viability. The in vitro antibacterial property was studied by well diffusion method against gram-positive bacteria Staphylococcus aureus (ATCC 25925) and gram-negative bacteria Escherichia coli (ATCC 25923). The inhibitory efficacy by scavenging free radical intermediates was evaluated by 1,1, diphenyl 2-picrylhydrazyl (DPPH) assay. The results of in vitro cytotoxicity showed biocompatibility towards L929 cells. Quercetin loaded Alginate/Chitosan nanoparticles inhibited the growth of microorganisms than pure quercetin. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging results have shown a high level of antioxidant property for encapsulated Quercetin in Alginate/Chitosan nanoparticles compared to free Quercetin. The findings of our study suggest that the developed ALG/CSNPs and Q-ALG/CSNPs possess the prerequisites and be proposed as a suitable system for delivering quercetin with enhanced therapeutic effectuality.

Mucus-Penetrating Alginate-Chitosan Nanoparticles Loaded with Berberine Hydrochloride for Oral Delivery to the Inflammation Site of Ulcerative Colitis.

The rectal enemas of berberine hydrochloride (BH) have emerged as one of the most effective strategies in the clinical treatment of ulcerative colitis (UC). However, oral dosages of BH exhibit a poor anti-inflammatory effect of UC, which may attribute to premature absorption of BH by the upper gastrointestinal tract. Moreover, the thick colonic mucus layer obstructs the penetration of the drug, resulting in low bioavailability to the inflammatory site of the colon. The aim of this study was to develop the mucus-penetrating sodium alginate-chitosan nanoparticles (SA-CS NPs) for oral delivery of BH to the site of colonic ulcer lesions. BH-loaded SA-CS NPs were developed through the ionic gelation method and analyzed for physicochemical characteristics, release performance, penetrability, site retention, and therapeutic efficacy. The results showed that the NPs have a particle size of 257 nm with a negative charge, presenting desired pH-dependent release behavior. The permeation studies elucidated that negatively charged SA-CS NPs had 2.9 times higher mucus penetration ability than positively charged CS NPs. An ex vivo retention study indicated the high retention of BH-SA-CS NPs at the colon site for more than 16 h. In vivo therapeutic effectiveness demonstrated that the prepared NPs could not only alleviate colonic injury by decreasing the disease activity index and colon mucosa damage index, but also improve the immunologic function by decreasing the spleen index. In conclusion, the BH-SA-CS NPs could enhance the mucus permeability and deliver drugs to the colonic inflammation site, providing new insights into improving the therapeutic effect of UC.

Chitosan nanoparticles containing the insecticide dimethoate: A new approach in the reduction of harmful ecotoxicological effects

Organophosphate insecticides such as dimethoate (DMT) are widely used in agriculture. As a side effect, however, these insecticides contaminate bodies of water, resulting in damage to aquatic organisms. The development of nanopesticides may be an innovative alternative in the control of agricultural pests, increasing effectiveness and reducing their toxicological effects. Based upon this, the present study has investigated encapsulated DMT in alginate chitosan nanoparticles (nanoDMT) and evaluated its toxicological effects on non-target organisms. The nanoparticles were characterized by DLS, NTA and AFM, as well as being evaluated by the release profile. Nanoparticle toxicity was also evaluated in comparison with DMT, empty nanoparticles and DMT (NP + DMT), and commercial formulations (cDMT), in the embryos and larvae of Danio rerio (zebrafish) according to lethality, morphology, and behavior. The nanoparticle control (NP) showed hydrodynamic size values of 283 ± 4 nm, a PDI of 0.5 ± 0.05 and a zeta potential of −31 ± 0.4 mV. For nanoparticles containing dimethoate, the nanoparticles showed 301 ± 7 nm size values, a PDI of 0.45 ± 0.02, a zeta potential of −27.9 ± 0.2 mV, and an encapsulation of 75 ± 0.32%, with slow-release overtime (52% after 48 h). The AFM images showed that both types of nanoparticles showed spherical morphology. Major toxic effects on embryo larval development were observed in commercial dimethoate exposure followed by the technical pesticide, predominantly in the highest tested concentrations. With regard to the toxic effects of sodium alginate/chitosan, although there was an increase for LC50–96 h concerning the technical dimethoate, the behavior of the larvae was not affected. The data obtained demonstrate that nanoencapsulated dimethoate reduces the toxicity of insecticides on zebrafish larvae, suggesting that nanoencapsulation may be safer for non-target species, by eliminating collateral effects and thus promoting sustainable agriculture.

Preparation and characterization of chloridazon-loaded alginate/chitosan nanocapsules.

In addition to the detrimental environmental effects of herbicides, including the pollution of soil, atmosphere, groundwater aquifers and run-off water, the lack of caution and direct or indirect exposure to these products can cause short-term and long-term human health effects. However, nanotechnology, with its many applications, can be very helpful in improving agriculture and reducing the side effects of chemicals used in agriculture. Nano-encapsulation of chemicals used in agriculture is one of the strategies to improve precision agriculture. Nano-encapsulated herbicides are controlled membrane systems in which the active ingredient is coated with semi-permeable membranes, which may be organic or inorganic polymers. In our study, chloridazon herbicide was selected as the active ingredient for Nano-encapsulation. Like many other agricultural herbicides, the major problem with this herbicide is environmental pollution and its adverse health effects. The ionic gelation method was used to synthesize nanocapsules consisting of alginate and chitosan for chloridazon encapsulation. Alginate-chitosan nanoparticles were prepared in a two-step process involving the ionotropic pre-gelation of an alginate core and then the formation of a chitosan polyelectrolyte complex. The alginate-chitosan nanocapsules containing chloridazon were synthesized at a size of 253 nm with a polydispersity index (PDI) of 0.266 and a zeta potential of -1.43 mV. The loading capacity and entrapment efficiency of these nanocapsules were 14% and 57%, respectively. The study of chloridazon release from formulated alginate-chitosan nanocapsules was performed using dialysis tube testing and UV spectroscopy. The results of our study showed controlled release of chloridazon from loaded alginate-chitosan nanocapsules. In general, alginate-chitosan nanocapsules as a Nano-carrier, have the potential to become a commercial formulation for chloridazon encapsulation. On the other hand, controlled release and increasing the duration of action of chloridazon, along with reducing the required dose, is promising in reducing the adverse health and environmental effects caused by chloridazon and improving precision agriculture.

QbD Supported Optimization of the Alginate-Chitosan Nanoparticles of Simvastatin in Enhancing the Anti-Proliferative Activity against Tongue Carcinoma.

The goal of the current study is to develop a chitosan alginate nanoparticle system encapsulating the model drug, simvastatin (SIM-CA-NP) using a novel polyelectrolytic complexation method. The formulation was optimized using the central composite design by considering the concentrations of chitosan and alginate at five different levels (coded as +1.414, +1, 0, −1, and −1.414) in achieving minimum particle size (PS-Y1) and maximum entrapment efficiency (EE-Y2). A total of 13 runs were formulated (as projected by the Design-Expert software) and evaluated accordingly for the selected responses. On basis of the desirability approach (D = 0.880), a formulation containing 0.258 g of chitosan and 0.353 g of alginate could fulfill the prerequisites of optimum formulation in achieving 142.56 nm of PS and 75.18% EE. Optimized formulation (O-SIM-CAN) was further evaluated for PS and EE to compare with the theoretical results, and relative error was found to be within the acceptable limits, thus confirming the accuracy of the selected design. SIM release from O-SIM-CAN was retarded significantly even beyond 96 h, due to the encapsulation in chitosan alginate carriers. The cell viability study and Caspase-3 enzyme assay showed a notable difference in contrast to that of plain SIM and control group. All these stated results confirm that the alginate-chitosan nanoparticulate system enhanced the anti-proliferative activity of SIM.

Anti-excitotoxicity and neuroprotective action of asiaticoside encapsulated polymeric nanoparticles in pilocarpine rodent seizure model

Asiaticoside (ASI), an ursane-type triterpenoid saponin, isolated from the memory enhancing herb Centella asiatica, is known for its neuroprotective activities. Here, the anti-excitotoxicity and neuroprotective effects of ASI encapsulated alginate chitosan nanoparticles (ACNPs) were evaluated in pilocarpine (PC) induced seizure in mice model. ACNPs were prepared by ionic gelation-polyelectrolyte complex method and their physicochemical characterization was carried out by TEM, SEM, DLS, XRD, and FTIR. Subsequently, their encapsulation efficiency (EE), in vitro drug release, cell viability, seizure score, DNA fragmentation, and mRNA expression of regulatory stress markers were evaluated. Membrane permeability of ACNPs in the brain, histopathology, and biological TEM and SEM analyses were also carried out. TEM of ACNPs showed spherical morphology with a particle size of 200–400 nm. DLS of ACNPs displayed an average size of 486.2 nm with polydispersity index (PDI) of 0.567 and zeta potential of –14.1 mV. ACNPs achieved high EE (&gt;90%) and controlled release (10%). Biological evaluation studies revealed ACNPs as non-toxic to mouse neural stem cells (mNSCs). They displayed enhanced brain permeability and attenuated seizure. Our results confirmed ACNPs as effective in crossing the brain membrane barrier and mitigating seizure severity induced by PC.

Preparation, characterization and releasing property of antibacterial nano-capsules composed of ε-PL-EGCG and sodium alginate-chitosan

Aquatic products with high moisture and protein content are susceptible to bacterial growth and spoilage. Searching for efficient and safe natural antibacterial agents to preserve aquatic products has been concerned widely. In this study, ε-poly-lysine-epigallocatechin gallate/sodium alginate-chitosan nanoparticles (ε-PL-EGCG/SA-CS NPs) were prepared using sodium alginate and chitosan as wall materials and ε-PL-EGCG as core material. The size of nanoparticles was about 200 nm and the encapsulation efficiency was 78.2%. Transmission electron microscopy (TEM) images confirmed the prepared spherical nanoparticles. Fourier transform infrared spectroscopy (FTIR) and multifunctional polycrystalline X-ray diffraction (XRD) spectra indicated that ε-PL-EGCG was encapsulated in the nanoparticles. Thermo-gravimetric analysis (TGA) illustrated that the thermal stability of encapsulated ε-PL-EGCG was improved more than that of bare ε-PL-EGCG. In addition, in vitro release assays showed that the ε-PL-EGCG was released continuously over 36 h. Bacteria inhibition results showed that the ε-PL-EGCG/SA-CS NPs significantly inhibited specific spoilage bacteria E3 that screened out of aquatic products, Escherichia coli and Staphylococcus aureus. In conclusion, ε-PL-EGCG/SA-CS NPs are an effective antibacterial means with wide application prospects in the field of aquatic products preservation.

Aljinat/Kitosan Nanopartiküllere Pemetrekset Adsorpsiyonu ve Kontrollü İlaç Salımı

Pemetrexed (PEM) is used for treatment of non-small cell lung cancer. However, PEM has disadvantages like fast elimination, low bioavailability, poor tumor cell selectivity, and penetration. Thus, there is a need for using pemetrexed delivery system to increase the anticancer effect of drug in lung cancer cells and to minimize its side effects. The purpose of this study is development of alginate/chitosan nanoparticles (ACNP) that have biodegradable and non-toxic structure for effective delivery of PEM for lung cancer therapy. In the present study, ACNP were prepared using the ionic gelation method, and pemetrexed was loaded via the adsorption method. Drug adsorption efficiency was calculated to be 57.80% and characterization studies were performed. In vitro drug release tests were carried out at pH levels of 5.5 and 7.4 with pemetrexed-loaded alginate/chitosan nanoparticles (PACNP) and free pemetrexed, and both the results were subsequently compared. Up to 11% release yield was observed at pH 5.5, and the yield reached up to 7% in pH 7.4 in the 25 hours. This nanoparticle system could be investigated in vitro and in vivo in further studies for controlled release of pemetrexed.

Evaluation of debridement effects of bromelain-loaded sodium alginate nanoparticles incorporated into chitosan hydrogel in animal models.

Objective(s):Bromelain, a mixture of proteolytic enzymes from pineapple (Ananas comosus) is known as a potential debriding agent in burn treatment. In this research, the debridement efficiency of chitosan hydrogel loaded by sodium alginate-chitosan nanoparticles (NPs) containing bromelain (Br 10%-AG-CS NPs) was evaluated in animal models. Materials and Methods:The NPs were prepared using the ionic gelation technique and their properties were identified. Then, the debridement effect of bromelain NPs incorporated into chitosan hydrogel was evaluated 4 hr after wound treatment in animal models. Results:The particle size of positively charged Br-AG-Cs NPs was about 390±25 nm. The encapsulation efficiency of bromelain into AG-CS NPs was about 92%. The in vitro release profile showed that the maximum release of bromelain from NPs occurred during the first 4 hr (70%). The hydrogel structure did not significantly affect the profile release of bromelain in the formulation. After 6 months of storage at 4 and 25 °C, the synthesized NPs indicated no significant changes in bromelain activity. It was found that Br 10%-Ag-Cs NPs-CS hydrogel had the most beneficial effects on reducing necrotic tissues and resulted in re-epithelialization compared with other treated groups (negative and positive control, CS hydrogel, and Br 10%-CS hydrogel). Conclusion:Therefore, using this novel formulation can be considered a potential debridement agent.

Synthesis, characterization, and antimicrobial activities of 3-HPAA-Alg-Chi nanoparticles

Encapsulation of bioactive compounds (e.g., phenolic acids) into nanoparticles is a well-received technique in the searching for new antimicrobial agents against multidrug-resistant pathogens. Encapsulation can be a good technique to maintain the stability of phenolic acids against environmental conditions. In this study, 3-hydroxyphenylacetic acid (3-HPAA) was encapsulated into alginate-chitosan nanoparticles with the ion gelation technique. The characterization of loaded and unloaded nanoparticles was performed via dynamic light scattering, Fourier transform infrared spectroscopy, and scanning electron microscopy. According to the results, 3-HPAA loaded nanoparticles have spherical shapes with a diameter range of 40-80 nm and an average hydrodynamic diameter of 361.0 +_ 69.8 nm. The loading of 3-HPAA was successfully achieved based on the Fourier transform infrared spectra and encapsulation percentage studies. The antimicrobial effect of the nanoparticles in solution forms was tested on P. aeruginosa, S. epidermidis, MRSA, and MSSA. The results demonstrated that the 3-HPAA loaded alginate chitosan nanoparticle solution showed elevated antimicrobial effect due to the pH change by treatment with 1% acetic acid, and it displayed bacteriocidal effects in a strain-specific and dose-dependent manner. Therefore, the 3-HPAA loaded alginate chitosan nanoparticle solution was produced successfully with the bacteriocidal effect against serious pathogenic bacteria.

T helper type 1 biased immune responses by PPE17 loaded core-shell alginate-chitosan nanoparticles after subcutaneous and intranasal administration

PurposeTuberculosis, a cost and life threatening disease, was being subjected for improving vaccine strategies beyond BCG. Thus, a novel particulate delivery system using alginate-coated chitosan nanoparticles including PPE17 protein and CpG were administered through intranasal (IN) and subcutaneous (SC) routes. MethodsThe encapsulated nanoparticles were first characterized for size, surface charge, encapsulation efficiency and in vitro release of PPE17 antigen. The nanoparticles were then administered intranasal and subcutaneously to evaluate the induction of systemic and/or mucosal immune responses in mice. ResultsAccording to our result, the mean size of nanoparticles was measured about 427 nm, and exhibited a negative zeta potential of −37 mV. Following subcutaneous and intranasal administration, the results from cytokines assay showed that an increasing in the level of IFN-γ, and adversely a decrease in the level of IL-4 (presumptive Th1 biased immune response) was happened and also a notable elicitation in IL-17 cytokine was observed. ConclusionIn conclusion, our study demonstrated that alginate-coated chitosan nanoparticles showed to be an effective way to improve BCG efficiency as booster strategy for subcutaneous vaccine, and also can induce strong immune responses as prime strategy through intranasal vaccination.

Microparticles based on alginate/chitosan/casein three‐dimensional system for oral insulin delivery

In the past, oral insulin has been developed to reduce the suffering of diabetic patients. However, the physiological barriers in gastrointestinal (GI) tract are the major challenges in oral delivery of insulin. In this study, a novel oral delivery system of insulin called NiM (NPs in MPs) has been developed to overcome the GI barriers, which based on a three‐dimensional system of biocompatible chitosan/alginate/casein. Alginate/chitosan nanoparticles (AC‐NPs) were firstly prepared by ionic pre‐gel method and complexation with polyelectrolytes. Then, they were subsequently coated with casein as a protective agent to form NiM, which could keep stability and physiological activity of insulin in gastric tract. The characterization of NiM showed stable hydrodynamic parameters, and the entrapment efficiency of insulin reached 51.1%. In vitro, only 13.5% of insulin was released in the simulated gastric fluid for the first 2 h. But about 57.4% of insulin was slowly released in the simulated intestinal fluid for 10 h. These results indicated that the coating of casein could increase stability of insulin in gastric tract and control release of insulin in intestinal tract. Furthermore, NiM provided a sustained and significant reduction of the blood glucose levels of diabetic mice. Overall, the results demonstrated that our formed NiM may be a promising oral delivery system of insulin for diabetic patients.

Application of Encapsulated Bacillus licheniformis Supplemented with Chitosan Nanoparticles and Rice Starch for the Control of Sclerotium rolfsii in Capsicum annuum (L.) Seedlings.

Rhizosphere encourages the survival and functioning of diverse microbial communities through the influence of plant roots. Likewise, the rhizobacterial functioning contribute to the growth and productivity of crop plants significantly. With the advancement of nanotechnology, the nanoparticles can expect to augment the performance of plant beneficial microorganisms including the rhizobacteria and hence have the promise to boost sustainable agricultural practices. In the present study, Bacillus licheniformis encapsulated in alginate-chitosan nanoparticles (CNPs) beads supplemented with rice starch (RS) has been evaluated for its plant growth enhancement and disease control properties. The encapsulated Bacillus licheniformis was initially characterized for indole-3-acetic acid (IAA) production, nitrogen fixing capacity, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase production and antifungal activity against Sclerotium rolfsii. In addition to this, the plant growth promoting and biocontrol properties of the encapsulated Bacillus licheniformis were also evaluated using Capsicum annuum (L.)(chilli) seedlings. From the results, the plants treated with encapsulated Bacillus licheniformis supplemented with CNPs were found to have maximum growth enhancement. At the same time, plants treated with encapsulated Bacillus licheniformis supplemented with CNPs and RS were found to have enhanced disease suppression. This revealed the application of encapsulated Bacillus licheniformis supplemented with CNPs and RS as a promising delivery system for agricultural applications.

Exploring Endolysin-Loaded Alginate-Chitosan Nanoparticles as Future Remedy for Staphylococcal Infections.

Endolysins are a novel class of antibacterials with proven efficacy in combating various bacterial infections, in vitro and in vivo. LysMR-5, an endolysin derived from phage MR-5, demonstrated high lytic activity in our laboratory against multidrug-resistant S. aureus (MRSA) and S. epidermidis strains. However, endolysin and proteins in general are associated with instability and short in vivo half-life, consequently limiting their usage as pharmaceutical preparation to treat bacterial infections. Nanoencapsulation of endolysins could help to achieve better therapeutic outcome, by protecting the proteins from degradation, providing sustained release, thus could increase their stability, shelf life, and therapeutic efficacy. Hence, in this study, the feasibility of alginate-chitosan nanoparticles (Alg-Chi NPs) to serve as drug delivery platform for LysMR-5 was evaluated. LysMR-5-loaded nanoparticles were prepared by calcium ion-induced pre-gelation of alginate core and its complexation with chitosan. The formation of nanoparticles was confirmed on the basis of DLS, zeta potential, and electron microscopy imaging. The LysMR-5-loaded nanoparticles presented a hydrodynamic diameter of 276.5 ± 42, a PDI of 0.342 ± 0.02, a zeta potential - 25mV, and an entrapment efficiency of 62 ± 3.1%. The potential ionic interaction between alginate, chitosan, and LysMR-5 was investigated by FT-IR and SEM-EDX analysis. Using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), nano-sized particles with characteristic morphology were seen. Different antibacterial assays and SDS-PAGE analysis showed no change in endolysin's structural integrity and bioactivity after entrapment. A direct antibacterial effect of blank Alg-Chi Nps, showing enhanced bactericidal activity upon LysMR-5 loading, was observed against S. aureus. At physiological pH (7.2), the release profile of LysMR-5 from Alg-Chi NPs showed a biphasic release and followed a non-Fickian release mechanism. The biocompatible nature as revealed by cytocompatibility and hemocompatibility studies endorsed their use as drug delivery system for in vivo studies. Collectively, these results demonstrate the potential of Alg-Chi NPs as nano-delivery vehicle for endolysin LysMR-5 and other therapeutic proteins for their use in various biomedical applications.

Evaluation of amygdalin-loaded alginate-chitosan nanoparticles as biocompatible drug delivery carriers for anticancerous efficacy

Amygdalin, despite possessing anticancerous properties, has been viewed as a controversial choice due to the presence of the cyanide group. Here, we synthesise and investigate the potential of alginate–chitosan nanoparticles (ACNPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer cells. Amygdalin loaded ACNPs were made with both anionic and cationic outer layer to further investigate charge dependency on drug delivery and cytotoxicity. ACNPs encapsulating amygdalin were monodisperse, colloidally stable with ~90% drug encapsulation efficiency and were entirely made from natural materials. The nanoparticles exhibited sustained drug release for a duration of 10 h and significant swelling rates in neutral and slightly acidic environments. The ACNPs successfully adhered to porcine mucin type II when assessed for its mucoadhesion and shown to transmigrate with an average velocity of 1.68 μm/s in uncoated channels, under biomimicked flow conditions. To investigate charge dependency on drug delivery and cytotoxicity, amygdalin loaded ACNPs were made with both anionic and cationic outer layer and assessed. ACNPs demonstrated greater yet sustained anti-cancerous effect on H1299 cell lines in a dose-dependent manner than free amygdalin suggesting greater cellular uptake of the former. In conclusion, biocompatible and biodegradable alginate–chitosan nanoparticles can be used as an effective drug delivery system for sustained and controlled amygdalin release with its improved cytotoxic effect on cancerous cells while protecting normal cells and tissues.