Continuous Transdermal Delivery of L-DOPA Based on a Self-Assembling Nanomicellar System.

PURPOSE: When levodopa (L-DOPA) is administered orally, it is eliminated from the body very quickly resulting in a series of sharp fluctuations in its blood concentrations. These frequent changes in blood levels are considered to be responsible for the development of late motor complications and dyskinesias, which are troubling clinical and treatment issues in Parkinson's disease. Transdermal drug delivery is a patient-compliant method for delivering therapeutics into the systemic circulation in a continuous and controlled manner. Transdermal delivery of L-DOPA can achieve continuous dopaminergic stimulation (CDS), thus reducing motor fluctuations. METHODS: However, there are two technical difficulties in the development of a transdermal patch for L-DOPA: (a) L-DOPA is poorly soluble in most pharmaceutically-acceptable solvents, and (b) L-DOPA has a limited permeability through the skin even from saturated solutions. We have, therefore, investigated the transdermal delivery of L-DOPA using an innovative self-assembling nano-micellar system (SANS), loaded with 2% L-DOPA and 1% carbidopa. RESULTS: In vitro testing as well as in vivo pharmacokinetic studies (multiple-dose regimen) in rabbits have demonstrated for the first time a significantly increased percutaneous permeation and systemic absorption of L-DOPA. CONCLUSIONS: It has therefore been proposed that either a once-daily or a twice-daily regimen could be therapeutically effective depending on the severity of the disease.

Comparative percutaneous permeation study using caffeine-loaded microemulsion showing low reliability of the frozen/thawed skin models.

The aim of this study was to explore the transdermal delivery potential of a new caffeine-containing microemulsion system. The skin permeability of caffeine (CAF) was measured in vitro using skin excised from three different animal species: rat, rabbit and pig. As shown, microemulsion containing 20% aqueous phase enhanced CAF permeation across fresh rat skin by one order of magnitude (Papp=8.2×10(-3) vs. 0.86×10(-3) cm/h; enhancement ratio=9.6). The permeability coefficient value, the cumulative permeation amount, and the percent of dose permeated after 24 h, decreased with the increase of water content from 60% to 80% in microemulsions due to the apparent increase in the droplet size. Importantly, differences were noted between caffeine transport rates across fresh and frozen/thawed pig skin whereas microemulsions delivered caffeine at similar rates across rat and rabbit skin, either fresh or frozen/thawed. It has been shown that the permeability of caffeine through frozen/thawed pig skin was abnormally high and was independent of its vehicle properties, i.e., its hydrophilic or lipophilic nature. It has been hypothesized that the reason for this abnormality is that porcine stratum corneum has a higher ceramide-to-cholesterol ratio compared to rat and rabbit skin. This unusual phenomenon observed in a non-freshly used porcine skin places a question mark on its suitability to in vitro evaluation of transdermal drug delivery systems.