Clarithromycin-Loaded Poly (Lactic-co-glycolic Acid) (PLGA) Nanoparticles for Oral Administration: Effect of Polymer Molecular Weight and Surface Modification with Chitosan on Formulation, Nanoparticle Characterization and Antibacterial Effects.

A Alper Öztürk,Evrim Yenilmez,Mustafa Güçlü Özarda

doi:10.3390/polym11101632

A Alper Öztürk, Evrim Yenilmez + Show 1 more

Open Access

https://doi.org/10.3390/polym11101632

Copy DOI

Journal: Polymers	Publication Date: Oct 9, 2019
Citations: 43	License type: CC BY 4.0

Affiliation: Anadolu University, Eskişehir City Hospital

Abstract

Clarithromycin (CLR) is a member of the macrolide antibiotic group. CLR has low systemic oral bioavailability and is a drug of class II of the Biopharmaceutical Classification System. In many studies, using nanoparticles (NPs) as a drug delivery system has been shown to increase the effectiveness and bioavailability of active drug substances. This study describes the development and evaluation of poly (lactic-co-glycolic acid) (PLGA) NPs and chitosan (CS)-coated PLGA NPs for oral delivery of CLR. NPs were obtained by nanoprecipitation technique and characterized in detail, and the effect of three molecular weights (Mw1: 7.000–17.000, Mw2: 38.000–54.000, Mw3: 50.000–190.000) of PLGA and CS coating on particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), and release properties etc. were elucidated. Gastrointestinal stability and cryoprotectant effect tests were performed on the NPs. The PS of the prepared NPs were in the range of 178 to 578 nm and they were affected by the Mw and CS coating. In surface-modified formulations with CS, the ZP of the NPs increased significantly to positive values. EE% varied from 62% to 85%, depending upon the Mw and CS coating. In vitro release studies of CLR-loaded NPs showed an extended release up to 144 h. Peppas–Sahlin and Weibull kinetic model was found to fit best for CLR release from NPs. By the broth microdilution test method, the antibacterial activity of the formulations was determined on Staphylococcus aureus (ATCC 25923), Listeria monocytogenes (ATCC 1911), and Klebsiella pneumoniae (ATCC 700603). The structures of the formulations were clarified by thermal (DSC), FT-IR, and 1H-NMR analysis. The results showed that PS, ZP, EE%, and dissolution rates of NPs were directly related to the Mw of PLGA and CS coating.

Highlights

Oral administration remains the most appropriate, useful, and convenient route for the delivery of most pharmaceutical active agents
Nanoparticles were prepared with three different molecular weights (Mw) of PLGA and chitosan
Detailed characterizations were made to all formulations and obtained results showed that the Mw of PLGA

Summary

Introduction

Oral administration remains the most appropriate, useful, and convenient route for the delivery of most pharmaceutical active agents. The research for approaches to improve the oral bioavailability of low permeable and low Polymers 2019, 11, 1632; doi:10.3390/polym11101632 www.mdpi.com/journal/polymers. The research for approaches to improve the oral bioavailability of low permeable and of low soluble compounds for oral administration continues. Using nanoparticles (NPs) as drug delivery system has taken place in the literature as one of these strategies [1]. By applying nanotechnology to soluble compounds for oral administration. Usingprocess nanoparticles drugalthough delivery medicine, NPs have been created to mimic orcontinues. NPs(NPs) vary as in size, system has taken place in the literature as one of these strategies [1]

Objectives

Methods

Results

Conclusion