TECHNOLOGIES TO ENHANCE AND MODIFY DELIVERY OF SMALL MOLECULES INTO AND ACROSS THE SKIN
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TitleTECHNOLOGIES TO ENHANCE AND MODIFY DELIVERY OF SMALL MOLECULES INTO AND ACROSS THE SKIN
AbstractSkin, being the most easily accessible route for drug delivery, provides an appealing alternative to the commonly utilized routes. Transdermal drug delivery has multiple benefits including bypassing first-pass metabolism and reduced fluctuations in plasma drug concentrations. However, for passive permeation of a drug molecule through the transdermal route, the molecule should ideally have a molecular weight of < 500 Da, moderate lipophilicity (log P 1-3), and a melting point of < 250 ºC. To achieve the therapeutic plasma concentration for a drug lacking these properties, several chemical and physical enhancement techniques can be implemented. Transcutol, oleic acid, and isopropyl myristate are examples of commonly used chemical penetration enhancers that have been studied in this research. Furthermore, we investigated physical enhancement techniques such as iontophoresis and microneedles to facilitate transdermal delivery. Conversely, microsponges were used to retard the delivery of drug into and across the skin by limiting the amount of drug available for absorption at a given time. In one of the aims, we have explored the effect of chemical penetration enhancers and microsponges on the delivery of a chemical warfare antidote: 4-phenyl butyric acid (4-PBA). We aimed to explore techniques that can modify the delivery of 4-PBA, so that a suitable formulation could be prepared to meet the exact drug delivery profile required to treat any given complication arising from arsenical chemical warfare. Dose titration is important in the case of baclofen (GABAb agonist) treatment since the effective dose varies depending on the individual and disease condition. Maltose microneedles and iontophoresis were investigated to deliver baclofen to reach a therapeutically relevant plasma concentration. Microneedles were observed to be the most promising method in delivering baclofen. Cannabidiol (CBD) is a non-psychoactive component of cannabis extract. CBD is used in the treatment of myriad skin disorders, including atopic dermatitis and psoriasis. Hence, there is a need for topical formulation development for the delivery of CBD. Semisolid preparations such as cream and emulgel of CBD were prepared and evaluated for percutaneous delivery of cannabidiol. Additionally, the effect of drug concentration, chemical penetration enhancers, and essential oils on drug delivery was explored in this study.