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.

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Remdesivir: A Closer Look at Its Effect in COVID-19 Pandemic

Pharmacology ◽

10.1159/000518440 ◽

2021 ◽

pp. 1-7

Author(s):

Huda R. Taha ◽

Nour Keewan ◽

Farah Slati ◽

Nour A. Al-Sawalha

Keyword(s):

Bronchoalveolar Lavage Fluid ◽

Clinical Evidence ◽

High Selectivity ◽

Lavage Fluid ◽

In Vivo Studies ◽

Nucleotide Analog ◽

Positive Results ◽

Adenosine Nucleotide

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of COVID-19 pandemic, resulted in significant harm to the affected countries in every aspect of life. The virus infected over 139 million patients and resulted in over 2.9 million deaths until April 16, 2021. New variants of this virus were identified that spread rapidly worldwide. Summary: Remdesivir, a prodrug of adenosine nucleotide analog, is an antiviral with a broad spectrum of activity that was tested on SARS and Middle East respiratory syndrome infections. In vitro studies conducted on SARS-CoV-2 revealed that remdesivir inhibited viral replication with high selectivity index in cell cultures. In vivo studies showed that remdesivir reduced viral load in bronchoalveolar lavage fluid and attenuated pulmonary infiltrates in infected animals. Further, remdesivir showed promising results in terms of clinical improvement, shortening the recovery time, mortality rate, and the duration of oxygen need, despite that some clinical trials did not reveal significant effect on remdesivir use. Several studies showed positive results of remdesivir against the new variants. Key Messages: Remdesivir showed a promising beneficial effect against new variants of SARS-CoV-2, but more clinical evidence is needed to confirm this effect.

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Poloxamer Modified Chitosan Nanoparticles for Vaginal Delivery of Acyclovir

Pharmaceutical Nanotechnology ◽

10.2174/2211738508666210108121541 ◽

2021 ◽

Vol 08 ◽

Author(s):

Sanjeevani Deshkar ◽

Sumit Sikchi ◽

Anjali Thakre ◽

Rupali Kale

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Sodium Tripolyphosphate ◽

Chitosan Nanoparticles ◽

Drug Uptake ◽

Mass Ratio ◽

Modified Chitosan ◽

Chitosan Nanoparticle ◽

Nanoparticle Formulation

Objective: The aim of the present study was to design a surface modified chitosan nanoparticle system for vaginal delivery of Acyclovir for effective drug uptake into vaginal mucosa. Method: Acyclovir loaded chitosan nanoparticles, with and without modification by poloxamer 407, were prepared by ionic gelation method. The effects of two independent variables, chitosan to sodium tripolyphosphate mass ratio (X1) and acyclovir concentration (X2), on drug entrapment in nanoparticles, were studied using 32 full factorial design. The surface response and counter plots were drawn to facilitate an understanding of the contribution of the variables and their interaction. The nanoparticles were evaluated for drug entrapment, size with zeta potential, morphological analysis by TEM, solid state characterization by FTIR, DSC, XRD, in vitro dissolution, in vitro cell uptake using HeLa cell line and in vivo vaginal irritation test in Wistar rats. Results: Chitosan nanoparticle formulation with chitosan to sodium tripolyphosphate mass ratio of 2:1 and acyclovir concentration of 2 mg/mL resulted in highest entrapment efficiency. Resulting nanoparticles revealed spherical morphology with particle size of 191.2 nm. The surface modification of nanoparticles with Poloxamer resulted in higher drug entrapment (74.3±1.5%), higher particle size (391.1 nm) as a result of dense surface coating, lower zeta potential and sustained drug release compared to unmodified nanoparticles. The change in the crystallinity of drug during nanoparticle formulation was observed in DSC and XRD study. Cellular uptake of Poloxamer modified chitosan nanoparticles was found to be higher than chitosan nanoparticles in HeLa cells. Safety of nanoparticle formulations by vaginal route was evident when tested in female rats. Conclusion: Conclusively, Poloxamer modified CH NP could serve as a promising and safe delivery system with enhanced cellular drug uptake.

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Oral insulin delivery by self-assembled chitosan nanoparticles: In vitro and in vivo studies in diabetic animal model

Materials Science and Engineering C ◽

10.1016/j.msec.2012.09.001 ◽

2013 ◽

Vol 33 (1) ◽

pp. 376-382 ◽

Cited By ~ 99

Author(s):

Piyasi Mukhopadhyay ◽

Kishor Sarkar ◽

Mousumi Chakraborty ◽

Sourav Bhattacharya ◽

Roshnara Mishra ◽

...

Keyword(s):

Animal Model ◽

Chitosan Nanoparticles ◽

Insulin Delivery ◽

Diabetic Animal ◽

In Vivo Studies ◽

Oral Insulin ◽

Self Assembled

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Bio-fabrication and statistical optimization of polysorbate 80 coated chitosan nanoparticles of tapentadol hydrochloride for central antinociceptive effect: in vitro–in vivo studies

Artificial Cells Nanomedicine and Biotechnology ◽

10.3109/21691401.2016.1163713 ◽

2016 ◽

Vol 45 (3) ◽

pp. 505-514 ◽

Cited By ~ 6

Author(s):

Ganesh B. Patil ◽

Sanjay J. Surana

Keyword(s):

Antinociceptive Effect ◽

Chitosan Nanoparticles ◽

Statistical Optimization ◽

In Vivo Studies ◽

Polysorbate 80

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Sustained Release of Levobupivacaine, Lidocaine, and Acemetacin from Electrosprayed Microparticles: In Vitro and In Vivo Studies

International Journal of Molecular Sciences ◽

10.3390/ijms21031093 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1093

Author(s):

Jian-Ming Chen ◽

Kuan-Chieh Liu ◽

Wen-Ling Yeh ◽

Jin-Chung Chen ◽

Shih-Jung Liu

Keyword(s):

Pain Relief ◽

Release Kinetics ◽

Human Fibroblasts ◽

Fracture Site ◽

In Vivo Studies ◽

Infrared Spectrometry ◽

Plga Microparticles ◽

Low Toxicity

In this study, we explored the release characteristics of analgesics, namely levobupivacaine, lidocaine, and acemetacin, from electrosprayed poly(D,L-lactide-co-glycolide) (PLGA) microparticles. The drug-loaded particles were prepared using electrospraying techniques and evaluated for their morphology, drug release kinetics, and pain relief activity. The morphology of the produced microparticles elucidated by scanning electron microscopy revealed that the optimal parameters for electrospraying were 9 kV, 1 mL/h, and 10 cm for voltage, flow rate, and travel distance, respectively. Fourier-transform infrared spectrometry indicated that the analgesics had been successfully incorporated into the PLGA microparticles. The analgesic-loaded microparticles possessed low toxicity against human fibroblasts and were able to sustainably elute levobupivacaine, lidocaine, and acemetacin in vitro. Furthermore, electrosprayed microparticles were found to release high levels of lidocaine and acemetacin (well over the minimum therapeutic concentrations) and levobupivacaine at the fracture site of rats for more than 28 days and 12 days, respectively. Analgesic-loaded microparticles demonstrated their effectiveness and sustained performance for pain relief in fracture injuries.

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Biodistribution and biocompatibility of glycyrrhetinic acid and galactose-modified chitosan nanoparticles as a novel targeting vehicle for hepatocellular carcinoma

Nanomedicine ◽

10.2217/nnm-2018-0455 ◽

2020 ◽

Vol 15 (2) ◽

pp. 145-161 ◽

Cited By ~ 4

Author(s):

Min Li ◽

Yan Wang ◽

Shuai Jiang ◽

Yang Gao ◽

Weijie Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Anticancer Agents ◽

Tumor Tissue ◽

Chitosan Nanoparticles ◽

Glycyrrhetinic Acid ◽

Modified Chitosan ◽

Inflammation Reaction ◽

Hcc Cells

Aim: The dual-ligand glycyrrhetinic acid and galactose-modified chitosan nanoparticles were designed to further improve the targeting capability to hepatocellular carcinoma (HCC). Materials & methods: The dual-ligand glycyrrhetinic acid and galactose-modified chitosan nanoparticles were fabricated by using ionic gelation method and their characteristics have been measured. Furthermore, the biodistribution and biocompatibility of this targeting vehicle were investigated in vitro and in vivo, respectively. Results: The targeting vehicle was specifically internalized into hepatoma cells in vitro and accumulated into tumor tissue in vivo with high efficacy. Moreover, the vehicle did not induce inflammation reaction and affect morphologies and organ functions. Conclusion: The targeting accumulation in HCC tissue and great biocompatibility of the dual-ligand modified chitosan nanoparticles highlight the potential of delivering anticancer agents into HCC cells.

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Lethal in vitro effects of optimized chitosan nanoparticles against protoscoleces of Echinococcus granulosus

Journal of Bioactive and Compatible Polymers ◽

10.1177/08839115211014219 ◽

2021 ◽

pp. 088391152110142

Author(s):

Nima Firouzeh ◽

Touba Eslaminejad ◽

Reza Shafiei ◽

Ashkan Faridi ◽

Majid Fasihi Harandi

Keyword(s):

Echinococcus Granulosus ◽

Exposure Time ◽

Chitosan Nanoparticles ◽

Parasitic Infection ◽

In Vivo Studies ◽

Wide Range ◽

In Vitro Effects ◽

Scolicidal Agent

Cystic Echinococcosis (CE) is a parasitic infection caused by the larval stage of Echinococcus granulosus. Exploring safe and effective scolicidal agents for the surgery is an urgent need for the successful treatment of CE. This study aimed to determine scolicidal activity of the synthesized chitosan nanoparticles. Physicochemical properties of synthesized nanoparticles were determined by using DLS, FTIR, and SEM. Different concentrations of chitosan nanoparticles from 125 to 1000 μg/ml were examined at different incubation times (10, 60, 120, and 180 min). Scolicidal and cytotoxic activity of chitosan nanoparticles were confirmed by eosin exclusion and hemolysis activity tests. FTIR spectra, zeta potential (+42 ± 2.08) and PDI (0.388 ± 0.034) value revealed that the chitosan nanoparticles were synthesized. Significant differences among the scolicidal effects of chitosan nanoparticles were observed in comparison to the control treatments and highest scolicidal activity was observed at 1000 μg/ml after 180 min exposure time. Hemolytic activity was not significant at all concentrations of chitosan nanoparticles. Our findings support the hypothesis that Chitosan nanoparticles have the potential to be a safe and efficient scolicidal agent candidate at very low concentrations and in a wide range of exposure time. Further in vivo studies are recommended to evaluate chitosan nanoparticle efficacy before clinical application.

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Novel Siwa propolis and colistin-integrated chitosan nanoparticles: elaboration; in vitro and in vivo appraisal

Nanomedicine ◽

10.2217/nnm-2019-0467 ◽

2020 ◽

Vol 15 (13) ◽

pp. 1269-1284

Author(s):

Yosra SR Elnaggar ◽

Bassma H Elwakil ◽

Salma S Elshewemi ◽

Moustafa Y El-Naggar ◽

Adnan A Bekhit ◽

...

Keyword(s):

Bacterial Resistance ◽

Chitosan Nanoparticles ◽

Entrapment Efficiency ◽

In Vivo Studies ◽

The Novel ◽

Propolis Extract ◽

High Entrapment Efficiency ◽

Incorporation Method

Aim: The present study aimed to formulate novel cremophore-decorated chitosan nanoparticles of colistin, integrated with Siwa propolis extract, to solve bacterial resistance to colistin. Materials & methods: The novel nanoformula was prepared using an incorporation method. Physicochemical assessment and in vivo studies of the selected nanoformulations were performed. Results: The nanoformulation exhibited a nanosize of 48.3 nm, high ζ potential (43.6 mV), high entrapment efficiency (75%) and complete bacterial growth eradication within 2 h (minimum inhibitory concentration = 6.25 μg/ml). Histological examination showed that incorporation of colistin into the nanoformulation could successfully prevent its nephrotoxicity. Conclusion: Tailoring of proper nanocarrier could successfully revert bacteria from being colistin-resistant to colistin-sensitive. The developed nanoformulation can be considered as a potential antibacterial agent in pneumonia treatment.

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