Physicochemical characterization and skin permeation of liposome formulations containing clindamycin phosphate

Abstract

This study was undertaken to evaluate the physicochemical properties and skin permeation of liposome formulations containing clindamycin phosphate (CP), especially when charge was imparted to the liposome. Five different liposome formulations were prepared using Phospholipon 85G (PL) and cholesterol (CH) by conventional lipid film hydration technique. Molar ratio of CH to PL was varied in the range of 0.16-1.0. Charged liposomes were prepared in the same way with addition of 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA) as charge carrier lipid for cationic or anionic charge of the liposome, respectively. Fresh full-thickness mice skin was taken and used for skin permeation study using Keshary-Chien diffusion cell with 1.77 cm(2) diffusion area at 37 degrees C. All liposome formulations prepared showed homogeneous size distribution with mean particle size of about 1 mum or less. Among the five liposome formulations prepared, formulation with the molar ratio of 0.5 showed the best result in the physicochemical properties such as polydispersity index, entrapment efficiency, size evolution, and ability of the liposome to retain CP as of entrapped in the vesicles. Charge-impartation of the formulation with cationic charge carrier lipid resulted in additional benefit in terms of inhibition of size evolution, the ability of the liposome to retain CP in the vesicles, and skin permeation. Steady state flux of the drug through the mice skin in the cationic liposome vesicles was 0.75 +/- 0.01 microg/cm(2)h while that in the control (dissolved into mixed alcohol solution) was 0.17 microg/cm(2)h. One half molar ratio of CH to PL was optimal in terms of physicochemical properties of the liposome formulation containing CP, and incorporation of cationic charge carrier lipid appeared to provide additional benefits for the stability of the liposome formulation and skin permeation of the drug.

Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape, and Functionality

“…This observation is in agreement with recent studies of liposomes. There, it was shown that cationic liposomes penetrate the skin more efficiently than anionic ones . The enhanced skin permeation of cationic liposomes was attributed to the “Donnan exclusion effect” and is related to the more efficient interaction of cationic particles with the negatively charged skin cells.…”

Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery

“…The positive charge of liposomes is helpful for binding in an ion-exchange manner with the negatively charged skin cells and hair follicles (Jung et al 2006). Shanmugam et al (2009) showed that the steady state flux of drug through the skin is higher for cationic liposomes, followed by anionic and neutral liposomes. The enhanced skin permeation of cationic liposomes is attributed to the permeation selectivity of skin, which is known as ‘Donnan exclusion effect’ (Shanmugam et al 2009).…”

“…Shanmugam et al (2009) showed that the steady state flux of drug through the skin is higher for cationic liposomes, followed by anionic and neutral liposomes. The enhanced skin permeation of cationic liposomes is attributed to the permeation selectivity of skin, which is known as ‘Donnan exclusion effect’ (Shanmugam et al 2009). Human skin SC is made up of lipids such as ceramides, cholesterol, free fatty acids and cholesteryl sulfate.…”

Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery

“…Since skin layers are known to be negatively charged [44], positively charged vesicles have been shown to improve penetration and retention in the skin [45–47]. It is therefore theorized that NVs as well as DNVs having a positive surface charge may fare better in terms of penetration into and retention in the skin as compared to similar neutral or negatively charged NVs [48, 49].…”