Polymeric micelle formulations for the cutaneous delivery of sirolimus: A new approach for the treatment of facial angiofibromas in tuberous sclerosis complex
| Autor: | Julie Quartier, Maria Lapteva, Stéphane Guerrier, Younes Boulaguiem, Yogeshvar N. Kalia |
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| Rok vydání: | 2021 |
| Předmět: |
Biodistribution
Swine Pharmaceutical Science 02 engineering and technology Polyethylene glycol Pharmacology Angiofibroma 030226 pharmacology & pharmacy Micelle 03 medical and health sciences chemistry.chemical_compound Tuberous sclerosis 0302 clinical medicine Drug Delivery Systems Tuberous Sclerosis medicine Animals Tissue Distribution Micelles Sirolimus Epidermis (botany) Chemistry 021001 nanoscience & nanotechnology medicine.disease Bioavailability Self-healing hydrogels 0210 nano-technology medicine.drug |
| Zdroj: | International journal of pharmaceutics. 604 |
| ISSN: | 1873-3476 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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