Modulation of Entrapment Efficiency and In Vitro Release Properties of BSA-Loaded Chitosan Microparticles Cross-Linked with Citric Acid as a Potential Protein-Drug Delivery System.

Natalia Sedyakina,Nataliya Feldman,Sergey Lutsenko,Grigory Avramenko,Andrey Kuskov,Kelly Velonia

doi:10.3390/ma13081989

Abstract

Microparticles, aimed for oral protein and peptide drug delivery, were prepared via emulsion cross-linking using citric acid as cross-linker and polyglycerol polyricinoleate as surfactant. A comparative study of the interaction between chitosan and citric acid and its effect on the resulting microparticle properties was performed using different chitosan-to-cross-linker mass ratios and pH-values during fabrication of the microparticles. Non-cross-linked and cross-linked microparticles were studied in terms of size (4–12 μm), zeta potential (−15.7 to 12.8 mV), erosion (39.7–75.6%), a model protein encapsulation efficiency (bovine serum albumin) (6.8–27.6%), and loading capacity (10.4–40%). Fourier transform infrared spectroscopy and X-ray diffraction confirmed the ionic interaction between the protonated amine groups of chitosan and the carboxylate ions of the cross-linking agent. Scanning electron microscopy revealed that the non-cross-linked microparticles had an uneven shape with wrinkled surfaces, while the cross-linked formulations were spherical in shape with smooth surfaces. On the basis of these data, the role of the surfactant and microparticle structure on the release mechanism was proposed. Control of the microparticle shape and release mechanisms is expected to be crucial in developing carriers for the controlled delivery of proteins and peptides.

Highlights

Injection remains nowadays one of the most commonly used delivery routes for administering most protein and peptide drugs
Our findings clearly demonstrated that all three factors, that is, increase of pH, increase of temperature, and concentration ratios, can be tuned in order to promote the formation of the chitosan–citric acid complex
Cross-linked chitosan microparticles were successfully prepared via the emulsification-cross-linking technique using polyglycerol polyricinoleate (PGPR) as surfactant and citric acid as cross-linking agent

Summary

Introduction

Injection remains nowadays one of the most commonly used delivery routes for administering most protein and peptide drugs It poses several disadvantages such as inconvenience to patients, need for several daily administrations owing to rapid elimination from circulation, risks of local allergy development followed by lipoatrophy, and rapid increase of protein concentration in the blood. The diverse delivery systems reported in the literature include liposomes, nanoparticles, microemulsions, and self-assembled polymeric nano and micro structures [6,7,8] In this aspect, it has been previously shown that drug delivery systems based on amphiphilic poly-N-vinylpyrrolidone possess low toxicity, high biocompatibility, and stability, and can effectively entrap different low molecular weight and protein therapeutic agents [9,10,11,12,13]

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Results

Conclusion