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Scientific article
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Polymeric micelle formulations for the cutaneous delivery of sirolimus: A new approach for the treatment of facial angiofibromas in tuberous sclerosis complex

Published inInternational journal of pharmaceutics, vol. 604, p. 120736
Publication date2021-07
Abstract

Facial angiofibromas are benign tumors characteristic of tuberous sclerosis complex. The disease involves the mTOR pathway and the cutaneous manifestation responds to topical treatment with sirolimus (SIR). However, there are no approved topical SIR products and extemporaneous formulations have been sub-optimal. The aims of this study were (i) to develop aqueous formulations of SIR loaded in polymeric micelles prepared using D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and (ii) to use the cutaneous biodistribution method, in conjunction with a new statistical approach, to investigate the feasibility of SIR delivery to the viable epidermis. Optimized micelle solutions and hydrogels (0.2%) were developed and stable at 4 °C for at least 6 and 3 months, respectively. Cutaneous delivery experiments (infinite and finite dose) using porcine skin demonstrated that both formulations increased SIR cutaneous bioavailability as compared to the control (ointment 0.2%). Moreover, studies with the micellar hydrogel 0.2% demonstrated SIR deposition in the viable epidermis with no transdermal permeation. These encouraging results confirmed that polymeric micelles enabled development of aqueous SIR formulations capable of targeted epidermal delivery. Furthermore, the cutaneous biodistribution provided a detailed insight into drug bioavailability in the different skin compartments that could complement/explain clinical observations of formulation efficacy.

eng
Keywords
  • Facial angiofibromas
  • Polymeric micelles
  • Sirolimus
  • Skin
  • TPGS
  • Thermodynamic activity
  • Topical delivery
Citation (ISO format)
QUARTIER, Julie et al. Polymeric micelle formulations for the cutaneous delivery of sirolimus: A new approach for the treatment of facial angiofibromas in tuberous sclerosis complex. In: International journal of pharmaceutics, 2021, vol. 604, p. 120736. doi: 10.1016/j.ijpharm.2021.120736
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ISSN of the journal0378-5173
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Technical informations

Creation06/22/2023 3:58:15 PM
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Update time06/23/2023 7:27:17 AM
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