Capsaicin and Piperine as Functional Excipients for Improved Drug Delivery across Nasal Epithelial Models.

The fruit from various pepper plants has been employed for the seasoning of food, as perfuming agents, and also as traditional medicines. Phytochemicals isolated from different pepper species have been found to modulate the pharmacokinetics of orally administered drugs. This study investigated the possibility to apply capsaicin and piperine (extracted alkaloids) as modulators for drug delivery across the nasal epithelium. Both a nasal epithelial cell line (RPMI 2650) and excised sheep nasal tissue were used as models to investigate the effects of the selected pepper compounds on drug permeation. FITC-dextran 4400 (MW 4400 Da) was used as a large molecular weight marker compound for paracellular transport, while rhodamine 123 was used as a marker compound that is a substrate for P-glycoprotein-mediated efflux. From the permeation results, it was clear that capsaicin inhibited P-glycoprotein efflux to a larger extent, while piperine showed drug permeation enhancement via other mechanisms. The cell cytotoxicity studies indicated that capsaicin was noncytotoxic up to a concentration of 200 µM and piperine up to a concentration of 500 µM as indicated by cell viability above 80%. The histological analysis of the excised nasal tissue and cultured RPMI 2650 cell layers indicated that some damage occurred after treatment with 200 µM capsaicin, but no changes were observed for piperine up to a concentration of 50 µM.

The In Vitro and In Vivo Effects of Hypoxis hemerocallidea on Indinavir Pharmacokinetics: Modulation of Efflux.

Hypoxis hemerocallidea (African potato) is a popular medicinal plant that has been used traditionally for the treatment of various disorders. Some HIV/AIDS patients use this traditional medicine together with their antiretroviral therapy. This study aimed to determine the impact of selected H. hemerocallidea materials (i.e., a commercial product, an aqueous extract, and biomass reference plant material) on the bidirectional permeability of indinavir across Caco-2 cell monolayers as well as the bioavailability of indinavir during an acute, single administration study in Sprague-Dawley rats. All of the selected H. hemerocallidea test materials demonstrated inhibition effects on indinavir efflux across Caco-2 cell monolayers, albeit to different extents. An increase in the bioavailability of indinavir was obtained in vivo when administered concomitantly with the H. hemerocallidea materials, albeit not statistically significantly. The change in bioavailability directly correlated with the in vitro permeability results. It can therefore be concluded that the change in permeability and bioavailability of indinavir was caused by efflux inhibition and this effect was dependent on the type of H. hemerocallidea material investigated, which was found to be in the following order: commercial product > aqueous extract > reference plant material. The clinical significance of the combined effect of efflux and metabolism inhibition by H. hemerocallidea should be determined in another in vivo model that expresses the cytochrome P450 3A4 enzyme.

Evaluation of Isolated Fractions of Aloe vera Gel Materials on Indinavir Pharmacokinetics: In vitro and in vivo Studies.

Aloe vera is a plant with a long history of traditional medicinal use and is consumed in different products, sometimes in conjunction with prescribed medicines. A. vera gel has shown the ability to modulate drug absorption in vitro. The aim of this study was to fractionate the precipitated polysaccharide component of A. vera gel based on molecular weight and to compare their interactions with indinavir pharmacokinetics. Crude polysaccharides were precipitated from a solution of A. vera gel and was fractionated by means of centrifugal filtration through membranes with different molecular weight cut-off values (i.e. 300 KDa, 100 KDa and 30 KDa). Marker molecules were quantified in the aloe leaf materials by means of nuclear magnetic resonance spectroscopy and the average molecular weight was determined by means of gel filtration chromatography linked to multi-angle-laser-light scattering and refractive index detection. The effect of the aloe leaf materials on the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers as well as indinavir metabolism in LS180 cells was measured. The bioavailability of indinavir in the presence and absence of the aloe leaf materials was determined in Sprague-Dawley rats. All the aloe leaf materials investigated in this study reduced the TEER of Caco-2 cell monolayers, inhibited indinavir metabolism in LS 180 cells to different extents and changed the bioavailability parameters of indinavir in rats compared to that of indinavir alone. These indinavir pharmacokinetic modulation effects were not dependent on the presence of aloverose and also not on the average molecular weight of the isolated fractions.

Herbal hepatotoxicity: current status, examples, and challenges.

INTRODUCTION: Herbal medicines have commonly been considered safe by the general public due to their natural origin and long history of traditional uses. In contrast to this belief, many plants produce toxic substances as secondary metabolites that are sometimes not easily distinguishable from the pharmacological active compounds. Some herbal medicines have been associated with adverse effects and toxic effects, including hepatotoxicity, which have been reversed upon discontinuation of the herbal medicine by the patient. AREAS COVERED: This review reflects on selected herbal medicines that are associated with hepatotoxic effects including a description of the phytochemicals that have been linked to liver injury where available. Although case studies are discussed where patients presented with hepatotoxicity due to use of herbal medicines, results from both in vitro and in vivo studies that have been undertaken to confirm liver injury are also included. EXPERT OPINION: Increasing evidence of herbal hepatotoxicity has become available through case reports; however, several factors contribute to challenges associated with causality assessment and pre-emptive testing as well as diagnosis of herb-induced liver injury.

Combination therapy of Western drugs and herbal medicines: recent advances in understanding interactions involving metabolism and efflux.

INTRODUCTION: While complementary and alternative medicine markets prosper with an increasing number of consumers of herbal medicines, there is an associated likelihood for herb-drug interactions to occur. Modulation of the activity of metabolic enzymes and/or active transporters by chemical constituents of herbal medicines may influence the therapeutic outcomes of coadministered allopathic medicines due to changes in their pharmacokinetic profiles. Although valuable information on herb-drug interactions is obtained by in vitro studies, such as the mechanisms of interaction, clinical significance of interactions is ultimately demonstrated by in vivo data. AREAS COVERED: The authors outline the mechanisms of herb-drug pharmacokinetic interactions briefly and discuss pharmacokinetic interactions between different therapeutic classes of Western drugs and herbal medicines. Furthermore, the authors also discuss herb-drug interactions from both in vitro and in vivo studies with specific focus on recent findings. EXPERT OPINION: Basic and clinical researches have contributed to the comprehension of the underlying mechanisms involved as well as the practical implications of herb-drug interactions. This provides a foundation for development of guidelines to inform patients about herb-drug interactions that can affect their health.