Preparation and pharmaceutical/pharmacodynamic evaluation of topical brucine-loaded liposomal hydrogel

Abstract

To reduce the toxicity and enhance the therapeutic efficacy of brucine, a traditional Chinese medicine for relieving arthritic and traumatic pain, in this study, a novel brucine-loaded liposomal hydrogel (BLH) formulation, suitable for topical application, was developed. Spherical liposomes composed of lecithin and cholesterol, with brucine, was prepared by a modified ethanol-dripping method. High percentage (over 80%) of encapsulated brucine in liposomes was obtained. Topical liposomal hydrogel formulations were prepared by further incorporation of the prepared liposomes into structured carbopol 940 hydrogels with the concentration of carbopol 1.0%, the ratio of glycerol to carbopol 8:1 and the brucine content 0.1%. The liposomal hydrogel formulations provided an obvious promotion for skin permeation of bruicne while for the free brucine in hydrogels (BH), there was no detectable drug permeation through the skin. The safety evaluation showed that the prepared BLH were no irritation to both the broken and integrity skin. Pharmacodynamic evaluation revealed that the BLH showed a better therapeutic efficacy than that of the BH. So, it can be concluded that the BLH developed here could represent a safe, effective and promising transdermal formulation for local treatment of analgesic and anti-inflammatory disease.

Analgesic and anti-inflammatory activity and pharmacokinetics of alkaloids from seeds of Strychnos nux-vomica after transdermal administration: Effect of changes in alkaloid composition

“…The hydrogel was prepared according to the previous paper with minor modification (Wang et al, 2009). Carbopol-940 powders (1 g) was weighted and added slowly into glycerin (8 g) under constant stirring by a glass rod.…”

“…The amount of brucine in the skin was determined according to the previously reported method (Wang et al, 2009). After skin permeation experiment, the residual formulation on skin was cleaned by physiological saline solution, and then was wiped dry.…”

“…A novel brucine-loaded liposome has been prepared and found to be effective in the xylene-induced ear edema test and acetic acid-induced writhing test following transdermal administration to mice (Qin et al, 2007). The liposomal hydrogel formulations were further developed and proved to represent a safe, effective and promising transdermal formulation for the local treatment of analgesic and anti-inflammatory diseases (Wang et al, 2009). The toxicity property of brucine is akin to that of strychnine.…”

Novel gel formulations with catanionic aggregates enable prolonged drug release and reduced skin permeation

“…Vesicular gel formulations have been shown to affect percutaneous penetration for a number of substances, e.g. lipophilic substances, alkaloids and local anaesthetics [18–20] …”

“…lipophilic substances, alkaloids and local anaesthetics. [18][19][20] The skin is an effective barrier against xenobiotics and the stratum corneum is often described with the brick-and-mortar model. [21] It was suggested that the lipids of traditional vesicles may penetrate the skin's intracellular lipid layer and modify these lamellae.…”