Development and In Vitro and In Vivo Evaluation of Microspheres Containing Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate for the Oral Delivery of Berberine Hydrochloride

Ying Li,Chunyan Zhu

doi:10.3390/molecules25081957

Abstract

Microspheres containing absorption enhancer (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate, SNAC) were developed to enhance the oral bioavailability of berberine hydrochloride (BER) with poor intestinal membrane permeability. Microspheres were prepared and characterized by particle size measurements, scanning electron microscopy, differential scanning calorimetry, BER payload and release, Caco-2 cell monolayer transport, and rat pharmacokinetics. The microspheres were spherical and had uniform size, high encapsulation efficiency and high loading capacity. In vitro release studies showed that BER-loaded microspheres had good sustained release characteristics. The Caco-2 cell monolayer transport study proved that SNAC could significantly enhance permeability of BER 2–3-fold. Pharmacokinetic studies demonstrated a 9.87-fold increase in area under the curve (AUC) of BER mixed with SNAC and a 14.14-fold increase in AUC of microspheres compared with BER alone. These findings indicate that SNAC is a promising absorption enhancer for oral delivery of BER in the form of both solution and microspheres.

Highlights

Berberine hydrochloride (BER) is a kind of quaternary ammonium type isoquinoline alkaloid; it is extracted from Coptis chinensis, a kind of plant, as both medicine and food
2B displays the Papp values of berberine hydrochloride (BER) mixed with sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) at different ratios for transport across the SNAC (2:3) improved by 2.11-fold and 2.64-fold
Caco-2 cell monolayer; compared with the Papp of BER solution, the Papp of BER mixed with SNAC

Summary

Introduction

Berberine hydrochloride (BER) is a kind of quaternary ammonium type isoquinoline alkaloid; it is extracted from Coptis chinensis, a kind of plant, as both medicine and food. BER shows a curative effect in the medication of various diseases. BER is adsorbed by protein, which makes it difficult to achieve effective concentrations [7,8,9,10,11]. As BER is slightly soluble in water and has poor biological membrane permeability, it shows poor intestinal absorption and very low oral bioavailability [12,13]. The conventional dosage forms of BER for oral administration cannot reach the therapeutic concentration with only a few administration times; it usually takes several months to take therapeutic effect [14].

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