Journal
POLYMERS
Volume 13, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/polym13060933
Keywords
microneedle; poloxamers; transdermal drug delivery; naltrexone
Categories
Funding
- National Institute of General Medical Sciences [R35GM124551]
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Transdermal delivery of naltrexone (NTX) can be enhanced by using thermosensitive polymer Poloxamer 407 (P407) gel, which may provide more sustained drug release. Microneedle treatment can enhance NTX permeation, and P407 gels show better permeability and more sustained release compared to aqueous solutions.
Transdermal delivery of naltrexone (NTX) can be enhanced using microneedles, although micropores generated this way can reseal by 48 h in humans, which prevents further drug delivery from a formulation. Poloxamer 407 (P407) is a thermosensitive polymer that may extend microneedle-assisted NTX delivery time by creating an in situ gel depot in the skin. We characterized gelation temperature, drug release, and permeation of P407 gels containing 7% NTX-HCl. To investigate microneedle effects on NTX-HCl permeation, porcine skin was treated with microneedles (600 or 750 mu m length), creating 50 or 100 micropores. The formulations were removed from the skin at 48 h to simulate the effect of micropores resealing in vivo, when drug delivery is blunted. Gelation temperature increased slightly with addition of NTX-HCl. In vitro NTX-HCl release from P407 formulations demonstrated first order release kinetics. Microneedle treatment enhanced NTX-HCl permeation both from aqueous solution controls and P407 gels. Steady-state flux was overall lower in the P407 conditions compared to the aqueous solution, though ratios of AUCs before and after gel removal demonstrate that P407 gels provide more sustained release even after gel removal. This may be beneficial for reducing the required application frequency of microneedles for ongoing treatment.
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