Fabrication of Quaternized Chitosan Nanoparticles Using Tripolyphosphate/Genipin Dual Cross-Linkers as a Protein Delivery System.

Kuo-Yu Chen,Si-Ying Zeng

doi:10.3390/polym10111226

Kuo-Yu Chen, Si-Ying Zeng

Open Access

https://doi.org/10.3390/polym10111226

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Journal: Polymers	Publication Date: Nov 5, 2018
Citations: 27	License type: CC BY 4.0

Affiliation: National Yunlin University of Science and Technology

Abstract

Various amounts of 2-((acryloyloxy)ethyl)trimethylammonium chloride were grafted onto chitosan (CS) via redox polymerization method to obtain water-soluble quaternized CS (QCS). The QCS nanoparticles loaded with bovine serum albumin (BSA) were then produced by ionic gelation with tripolyphosphate (TPP) and further covalently cross-linked with genipin. The formation of QCS nanoparticles was optimized as a function of monomer grafting yield, QCS/TPP weight ratio, and QCS/genipin weight ratio by Box-Behnken design and response surface methodology. The results showed that QCS nanoparticles prepared with a grafting yield of 50%, QCS/TPP weight ratio of 7.67, and QCS/genipin weight ratio of 60 had a particle size of 193.68 ± 44.92 nm, polydispersity of 0.232, zeta potential of +23.97 mV and BSA encapsulation efficiency of 46.37 ± 2.89%, which were close to the predicted values from mathematical models. In vitro drug release studies at pH 1.2 and pH 7.4 exhibited that the release rate of BSA was significantly decreased and the release period was significantly prolonged after QCS nanoparticles cross-linking with genipin. Therefore, QCS nanoparticles cross-linked with TPP/genipin dual cross-linkers may be a promising protein drug carrier for a prolonged and sustained delivery.

Highlights

Stimuli-sensitive hydrogels have attracted considerable attention as carriers of drug delivery systems because of the controlled release of drugs upon triggering by external stimuli, including temperature, pH, ionic strength of the surrounding fluid, chemicals, and applied electric/magnetic field [1].Chitosan (CS) is a natural linear polysaccharide derived by partial deacetylation of chitin
In vitro drug release studies at pH 1.2 and pH 7.4 exhibited that the release rate of bovine serum albumin (BSA) was significantly decreased and the release period was significantly prolonged after quaternized CS (QCS) nanoparticles cross-linking with genipin
The initial burst release from nanoparticles was tried to reduce by further chemical cross-linking with genipin

Summary

Introduction

Stimuli-sensitive hydrogels have attracted considerable attention as carriers of drug delivery systems because of the controlled release of drugs upon triggering by external stimuli, including temperature, pH, ionic strength of the surrounding fluid, chemicals, and applied electric/magnetic field [1].Chitosan (CS) is a natural linear polysaccharide derived by partial deacetylation of chitin. Stimuli-sensitive hydrogels have attracted considerable attention as carriers of drug delivery systems because of the controlled release of drugs upon triggering by external stimuli, including temperature, pH, ionic strength of the surrounding fluid, chemicals, and applied electric/magnetic field [1]. In acidic media (pH < 6.5), CS becomes a cationic polyelectrolyte due to protonation of the amino groups [2]. CS has been explored as carriers for mucosal delivery of drugs and bioactive molecules, such as ocular drugs, antipsychotic drugs, peptide, proteins, oligonucleotides, and DNA, due to its mucoadhesive property [4,5,6]. CS is only dissolved in an acid solution (pH < 6.5), which may damage cells and bioactive agents [8]. CS will be ineffective as an absorption enhancer at physiological pH due to its loss of cationic nature [9]

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Results

Conclusion