Chitosan Nanoparticle-Based System: A New Insight into the Promising Controlled Release System for Lung Cancer Treatment

Lung cancer has been recognized as one of the most often diagnosed and perhaps most lethal cancer diseases worldwide. Conventional chemotherapy for lung cancer-related diseases has bumped into various limitations and challenges, including non-targeted drug delivery, short drug retention period, low therapeutic efficacy, and multidrug resistance (MDR). Chitosan (CS), a natural polymer derived from deacetylation of chitin, and comprised of arbitrarily distributed β-(1-4)-linked d-glucosamine (deacetylated unit) and N-acetyl-d-glucosamine (acetylated unit) that exhibits magnificent characteristics, including being mucoadhesive, biodegradable, and biocompatible, has emerged as an essential element for the development of a nano-particulate delivery vehicle. Additionally, the flexibility of CS structure due to the free protonable amino groups in the CS backbone has made it easy for the modification and functionalization of CS to be developed into a nanoparticle system with high adaptability in lung cancer treatment. In this review, the current state of chitosan nanoparticle (CNP) systems, including the advantages, challenges, and opportunities, will be discussed, followed by drug release mechanisms and mathematical kinetic models. Subsequently, various modification routes of CNP for improved and enhanced therapeutic efficacy, as well as other restrictions of conventional drug administration for lung cancer treatment, are covered.

Development and Optimization of Chitosan Nanoparticle-Based Intranasal Vaccine Carrier

Chitosan is a natural polysaccharide, mainly derived from the shell of marine organisms. At present, chitosan has been widely used in the field of biomedicine due to its special characteristics of low toxicity, biocompatibility, biodegradation and low immunogenicity. Chitosan nanoparticles can be easily prepared. Chitosan nanoparticles with positive charge can enhance the adhesion of antigens in nasal mucosa and promote its absorption, which is expected to be used for intranasal vaccine delivery. In this study, we prepared chitosan nanoparticles by a gelation method, and modified the chitosan nanoparticles with mannose by hybridization. Bovine serum albumin (BSA) was used as the model antigen for development of an intranasal vaccine. The preparation technology of the chitosan nanoparticle-based intranasal vaccine delivery system was optimized by design of experiment (DoE). The DoE results showed that mannose-modified chitosan nanoparticles (Man-BSA-CS-NPs) had high modification tolerance and the mean particle size and the surface charge with optimized Man-BSA-CS-NPs were 156 nm and +33.5 mV. FTIR and DSC results confirmed the presence of Man in Man-BSA-CS-NPs. The BSA released from Man-BSA-CS-NPs had no irreversible aggregation or degradation. In addition, the analysis of fluorescence spectroscopy of BSA confirmed an appropriate binding constant between CS and BSA in this study, which could improve the stability of BSA. The cell study in vitro demonstrated the low toxicity and biocompatibility of Man-BSA-CS-NPs. Confocal results showed that the Man-modified BSA-FITC-CS-NPs promote the endocytosis and internalization of BSA-FITC in DC2.4 cells. In vivo studies of mice, Man-BSA-CS-NPs intranasally immunized showed a significantly improvement of BSA-specific serum IgG response and the highest level of BSA-specific IgA expression in nasal lavage fluid. Overall, our study provides a promising method to modify BSA-loaded CS-NPs with mannose, which is worthy of further study.

SYNTHESIS OF ENCAPSULATED CHROMOLAENA ODORATA LEAF EXTRACT IN CHITOSAN NANOPARTICLE BY USING IONIC GELATION METHOD AND ITS ANTIOXIDANT ACTIVITY

Objective: The aim of this study was to determine the antioxidant activity of Chromolaena odorata. Methods: Encapsulation of Chromolaena odorata leaf extract by nano chitosan was synthesized by using chitosan and NaTPP as the crosslinking agent. The antioxidant activity was conducted by using the DPPH method. Results: Nanoparticles of Chromolaena odorata leaf extract has an average diameter of 675±218 nm and+23.4±7.14 mV of zeta potential. The antioxidant activity of its extract was 0.86 ppm, while its nanoparticle has the better antioxidant activity of 0.21 ppm. Conclusion: Nanoparticles of Chromolaena odorata have very strong antioxidant activity and the potential to be external antioxidants.

Self-Assembly of Soluble Chitosan Derivatives Nanoparticles for Vaccine: Synthesis, Characterization and Evaluation

Herein, a novel chitosan derivative nanoparticle was proposed to function as a delivery carrier. First of all, an improvement was made to the way N-2-hydroxypropyl trimcthyl ammonium chloride chitosan (N-2-HACC) was synthesized. Moreover, the solution to one-step synthesis of N-2-HACC from chitosan (CS) was developed. Different from the previous report, the synthesis process was simplified, and there was a reduction in the amount of 2,3-epoxypropyl trimethyl ammonium chloride (EPTAC) used. With its excellent water solubility maintained, the relatively low degree of substitution was controlled to facilitate the cross-linking reaction. The results obtained from 1H-NMR, FTIR spectroscopy, and XRD indicated a smooth EPTAC onto CS for the formation of N-2-HACC with 59.33% the degree of substitution (DS). According to our results, N-2-HACC could be dissolved in various organic solvents, deionized water, 1% acetic acid aqueous solution, and others at room temperature. Finally, a novel chitosan nanoparticle material was prepared using the self-assembly method with β-glycerophosphate sodium (β-GC), with excellent immune properties achieved, thus providing a new strategy for chitosan self-assembled nanoparticles.

Salmonella chitosan nanoparticle vaccine administration is protective against Salmonella Enteritidis in broiler birds

Salmonella control strategies include vaccines that help reduce the spread of Salmonella in poultry flocks. In this study we evaluated the efficacy of administering a live Salmonella vaccine followed by a killed Salmonella chitosan nanoparticle (CNP) vaccine booster on the cellular and humoral immunity of broilers. The CNP vaccine was synthesized with Salmonella Enteritidis (S. Enteritidis) outer-membrane-proteins (OMPs) and flagellin-proteins. At d1-of-age, one-hundred-sixty-eight chicks were allocated into treatments: 1) No vaccine, 2) Live vaccine (Poulvac®ST), 3) CNP vaccine, 4) Live+CNP vaccine. At d1-of-age, birds were orally vaccinated with PBS, Live vaccine, or CNP. At d7-of-age, the No vaccine, Live vaccine and CNP vaccine groups were boosted with PBS and the Live+CNP vaccine group was boosted with CNP. At d14-of-age, birds were challenged with 1×109 CFU/bird S. Enteritidis. There were no significant differences in body-weight-gain (BWG) or feed-conversion-ratio (FCR). At 8h-post-challenge, CNP and Live+CNP-vaccinated birds had 17% and 24% greater levels (P<0.05) of anti-Salmonella OMPs IgA in bile, respectively, compared to control. At d28-of-age, CNP, Live, and Live+CNP-vaccinated birds had 33%, 18%, and 24% greater levels (P<0.05) of anti-Salmonella OMPs IgA in bile, respectively, compared to control. At d14-of-age, Live+CNP-vaccinated birds had 46% greater levels (P<0.05) of anti-Salmonella OMPs IgY in serum, compared to control. At d21-of-age, splenocytes from CNP and Live-vaccinated birds had increased (P<0.05) T-lymphocyte proliferation at 0.02 mg/mL OMPs stimulation compared to the control. At d28-of-age, CNP and Live+CNP-vaccinated birds had 0.9 Log10 CFU/g and 1 Log10 CFU/g decreased S. Enteritidis cecal loads (P<0.05), respectively, compared to control. The CNP vaccine does not have adverse effects on bird’s BWG and FCR or IL-1β, IL-10, IFN-γ, or iNOS mRNA expression levels. It can be concluded that the CNP vaccine, as a first dose or as a booster vaccination, is an alternative vaccine candidate against S. Enteritidis in broilers.