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Development of a Nanoliposomal Transdermal Drug Delivery System
- Julia Finkel, M.D.
- Zenaide Quezado, M.D.
- Don deVoe, Ph.D.
- Renee Hood, Ph.D.
- Luis Almeida, M.D., Ph.D.
- Alfia Khaibullina, Ph.D.
- Sayuri Kamimura, MS
- Li Wang, M.D., Ph.D.
Transdermal drug administration holds great utility for pain-free and non-invasive drug delivery. In addition to obviating the need for injections, it has several advantages over the oral route. Transdermal drug delivery bypasses the liver first-pass effect that can prematurely metabolize drugs, is noninvasive, can be self-administered for longer periods of time, and greatly improves patient compliance. Transdermal delivery of free Dex is limited by poor transport across the structured lipid/protein matrix that comprises the stratum corneum (SC) layer, with reduced bioavailability due to the limited penetration of free drug through the skin. Nanoparticle-enhanced delivery offers a solution to this challenge. Organic and inorganic nanoparticles in the 20~40nm range can successfully traverse the SC and enter circulation for systemic drug delivery, but they suffer from high toxicity and low drug loading levels. In contrast, liposomal nanoparticles have low innate toxicity, support high drug payloads, and can extend a drug’s period of action by significantly increasing blood circulation times and taking advantage of nanoparticle-controlled release of drug at the site of action. However, conventional liposomal particles either cannot traverse the SC in significant numbers or become lysed by the SC, negating their ability to extend duration of action through nanoparticle-mediated drug release. Here we propose the development of a unique nanoliposomal Dex/opioid polypharmaceutical enabling direct transdermal administration and extended duration of action, with Dex serving as an adjunct to opioid therapy.
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