Preparation and application of pH-responsive composite hydrogel beads as potential delivery carrier candidates for controlled release of berberine hydrochloride.

Jiande Gao,Xiong Liu,Dongying Fan,Ping Song,Shudan Zhang

doi:10.1098/rsos.200676

Abstract

For improving the effective concentration of berberine hydrochloride (BH) in the gastrointestinal tract, a series of pH-responsive hydrogel beads were prepared based on carboxymethylstarch-g-poly (acrylic acid)/palygorskite/starch/sodium alginate (CMS-g-PAA/PGS/ST/SA) in the present work. The developed hydrogel beads were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TG). Effect of palygorskite (PGS) content on the swelling properties of hydrogel beads and BH cumulative release were discussed. The pH responsiveness of hydrogel beads was also investigated in different media. Results illustrated that swelling of hydrogel beads and BH cumulative release from hydrogel beads were obviously affected by PGS content. The swelling ratio and BH cumulative release of composite hydrogel beads remarkably slowed down with PGS content increasing in the range from 10 to 40 wt%. The composite hydrogel beads were pH-responsive. At pH 7.4, the swelling ratio and BH cumulative release from composite hydrogel beads were the fastest among the dissolution media of pH 1.2, pH 6.8 and pH 7.4. The BH cumulative release from hydrogel beads was related to the swelling and relaxation of composite hydrogel beads and could be fitted better by the Higuchi model. The obtained composite hydrogel beads could be potentially used for the development of BH pharmaceutical dosage forms.

Highlights

Berberine hydrochloride (BH), an isoquinoline alkaloid, can be extracted from a variety of Chinese medicines such as Hydrastis canadensis, Berberis aristata, Phellodendron amurense and Tinospora cordifolia [1]
Based on the information obtained from figure 1, it could be concluded that PAA chains grafted onto the Carboxymethyl starch (CMS), PGS participated in the grafting copolymerization reaction, and BH was filled in the CMS-g-PAA/10% PGS/ST/sodium alginate (SA) hydrogel beads and interacted with the composite hydrogel beads
A series of new pH-responsive composite hydrogel beads were successfully developed in order to improve the effective concentration of BH in the gastrointestinal tract

Summary

Introduction

Berberine hydrochloride (BH), an isoquinoline alkaloid, can be extracted from a variety of Chinese medicines such as Hydrastis canadensis, Berberis aristata, Phellodendron amurense and Tinospora cordifolia [1]. BH could be proven to exert the effects on mycotic infection, heart and cardiovascular diseases, and diabetic renopathy [7]. These novel bioactivities have evoked a strong desire on the potential use of BH. The further clinical application of BH is seriously limited due to its poor water-solubility and high polarity as an alkaloid [8,9], which resulted in low gastrointestinal absorption and bioavailability after oral administration [10]. To effectively increase the concentration of BH in the gastrointestinal tract and absorption, a new strategy for improving BH-release involves the utilization of drug carriers

Objectives

Results

Conclusion