Thermosensitive Gels Used to Improve Microneedle-Assisted Transdermal Delivery of Naltrexone

Abstract

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 μm 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.

Application of microneedle patches for drug delivery; doorstep to novel therapies

“… 79 Commensurate with these comments, any disruption on the expected local temperature can lead to undesirable aggregation or disassembly that limits the application of thermoresponsive materials in the clinical setting. 79 …”

“…Data showed that the increase of ambient temperature up to 27°C caused P407 gelation and a steady release rate up to 48 h. The aqueous-loaded NTX-HCl had a higher and fast release rate. 79 Commensurate with these comments, any disruption on the expected local temperature can lead to undesirable aggregation or disassembly that limits the application of thermoresponsive materials in the clinical setting. 79 Due to distinct pH values in different parts of the body and cellular segments, biomaterials with the ability to respond to acidic or physiological conditions have been developed.…”

“…79 Commensurate with these comments, any disruption on the expected local temperature can lead to undesirable aggregation or disassembly that limits the application of thermoresponsive materials in the clinical setting. 79 Due to distinct pH values in different parts of the body and cellular segments, biomaterials with the ability to respond to acidic or physiological conditions have been developed. 80 The pH-responsive materials are materials with acidic or alkaline groups (PKa value between 3 and 10) and ionized with electrostatic interactions following the alteration of environmental pH.…”

“…have been used to deliver drugs into the target area. 77 , 78 In an experiment, the permeability of porcine skin was successfully increased after the insertion of a solid microneedle with 600 µm length for 48 h. 79 To this end, NTX-HCl was encapsulated in poloxamer 407 (P407) and applied to the skin. Data showed that the increase of ambient temperature up to 27°C caused P407 gelation and a steady release rate up to 48 h. The aqueous-loaded NTX-HCl had a higher and fast release rate.…”

Recent Advances in Polymer Microneedles for Drug Transdermal Delivery: Design Strategies and Applications

“…This type of microneedle can improve the ability of cross skin transmission. [ 54 ] They can be fabricated from silicon, metal, and polymer ( Table 3 ), and the morphology of some reported solid MNs are listed in Figure . [ 64 ] Silicon is the first material used to manufacture MNs.…”