Characterization and evaluation of novel nano/meso-particulate formulations for application to the skin

Abstract

The use of nano/meso-particles (NP/MP) as constituent of topical formulations of drug and cosmetics has been a topic of considerable interest for the past 20 years. However, the transport mechanism of nanoparticle-associated drug/active following topical application on the skin is still unclear. No general answers have been obtained to such questions as the depth of intact NP penetration into the skin, the skin distribution of active substances, and the fate of the vehicles on/in the skin. The main objective of this thesis, therefore, was to observe the in vitro penetration of fluorescently-labeled nanoparticle vehicle and “active” on/within the skin by using laser scanning confocal microscopy (LSCM). Furthermore, the concentration profile of the “active” in the outermost skin layer, stratum corneum, has been assessed by using tape stripping technique combined with HPLC analysis. The factors, including particle size, hydrophobicity, shell thickness of nanocapsules and surface charge, have been investigated with regard to their abilities to influence the penetration of “active” into the skin. The methods for NP preparation and characterization have also been developed. The results demonstrated that the delivery of “active” into the stratum corneum from NP/MP were influenced by a number a factors, including particle size, hydrophobicity, surface charge and shell thickness of capsules. The “active” delivery (i) is greater from larger vectors; (ii) increases as the hydrophobicity of NP/MP increases; (iii) is favoured by cationic NP; (iv) is favoured from capsules with a smaller shell thickness. NP vehicle and “active” mainly co-localize in skin “furrows” and around hair follicles after topical application. No evidence shows NP penetrate beyond the superficial layer of the skin. In the stratum corneum, the “active” remains in part associated with NP, but the release f the “active” clearly occurs to some extent followed by its penetration into deep layers of the stratum corneum. Overall, through this work, the fate of nanoparticle vehicle and the “active” has been distinguished and the physicochemical properties of the nanoparticles that determine their behaviour once applied to the skin, and the kinetics with which an “active” is released, has also been understood.

Date of Award	1 Nov 2008
Original language	English
Awarding Institution	University of Bath
Supervisor	Richard Guy (Supervisor)