Physical methods for topical skin drug delivery: concepts and applications

Abstract

Topical drug delivery is an interesting approach to treat skin diseases and to avoid pain and low patient compliance in cases where a systemic delivery is required. However, the stratum corneum, which is the outermost skin layer, strongly protects the body from the entrance of substances, especially those hydrophilic. In this context, different physical methods have been studied to overcome the stratum corneum barrier and facilitate penetration of drugs into or through the skin. Among them, iontophoresis, low-frequency ultrasound and microneedles have been widely employed for transdermal drug delivery. More recently, they are also studied to aid in the treatment of dermatological disorders, such as skin tumors and inflammation. Basically, iontophoresis refers to the movement of charged and non-charged hydrophilic molecules through the skin due to the application of a low constant electric current and the contributions of electromigration and electroosmosis. In low-frequency ultrasound, cavitation is the main mechanism for skin permeabilization that consists on the formation of microbubbles that disorganize the stratum corneum. Microneedles are microprojections, minimally invasive, that can be designed with different lengths, materials and geometry to increase skin permeability. In this review, concepts, mechanisms and applications of these three physical methods will be presented and discussed with focus on their use in dermatological treatments. Moreover, comparative studies using different physical methods will be presented and also some clinical perspectives will be addressed.

Nanotechnology approaches in the current therapy of skin cancer

“…The superior antitumor activity of the MAGE-A1-targeted DOX-loaded liposomes was observed in tumors with positive M1/A1 expression [345]. The functionalization of the 5-FU-liposomes with cetuximab was also shown to improve antitumor effects with a great reduction in melanoma tumor volume (N60%) compared to that induced by the free 5-FU or control liposomes [346].…”

Ultrasound-responsive polymer-based drug delivery systems

“…Additionally, recent improvements in physical permeation enhancement technologies (i.e., electroporation, iontophoresis, and microneedle array patches) have led to an increased amount of interest in transdermal drug delivery [163][164][165][166][167][168]. It can be expected that the combination of ultrasound-responsive polymeric formulations with these advanced technologies might further enhance transdermal drug delivery [156,169].…”

The transdermal penetration of novel amphiphilic MTC-Y carrier

“…The epidermis consist of two layers: stratum corneum (SC) and viable epidermisor germinative layer (GL) where cells divide and differentiate into the keratinized cells of SC 6 .The epidermal barrier protects the body from excessive water loss and the entry of exogenous substances. An essential component of the permeability barrier is the extracellular lipid matrix of the SC.This lipid matrix consists of numerous lipids including ceramides, free fatty acidsand cholesterol.…”

“…Numerous skin penetration enhancers are proposed to improve topically applied drug delivery. Hybrid terpene-amino acid enhancers, esters of terpene alcohols, niosomesdendrimer nanoparticles, peptides [8][9][10][11][12][13][14] .The another method for increased/decreased skin permeability is the use of mechanical factors such as electric devices or ultrasound, iontophoresis, sonophoresis 6,15,16 .…”