Self-assembled mPEG-hexPLA polymeric nanocarriers for the targeted cutaneous delivery of imiquimod

Article Article scientifique Article Self-assembled mPEG-hexPLA polymeric nanocarriers for the targeted cutaneous delivery of imiquimod eng 2019 author Lapteva Maria 631860 author Mignot Margaux 771549 author Mondon Karine author Möller Michael author Gurny Robert 24779 author Kalia Yogeshvar 0000-0001-9049-5489 503798 553-562 10.1016/j.ejpb.2019.01.008 30641138 0939-6411 mPEG-hexPLA micelles have shown their ability to improve delivery and cutaneous bioavailability of a wide range of poorly water soluble and lipophilic molecules. Although poorly water soluble, imiquimod (IMQ) is only moderately lipophilic and it was decided to investigate whether mPEG-hexPLA polymeric micelles could be used as a drug delivery system for this "less than ideal" candidate for encapsulation. Nanosized IMQ micelles (dn = 27 nm) were formulated and characterized. Moreover, the innovative use of size exclusion chromatography allowed the exact drug localization inside the formulation to be determined; it appeared that the use of acetic acid to solubilize IMQ led to a higher IMQ content outside the micelle than inside. IMQ micelles (0.05%) were formulated in a gel using carboxymethyl cellulose (CMC). In vitro application of this formulation to porcine and human skin led to promising delivery results. IMQ deposition in human skin was 1.4 ± 0.4 µg/cm2 while transdermal permeation was only 79 ± 19 ng/cm2: the formulation displayed >17-fold selectivity for cutaneous deposition over transdermal permeation. The optimized 0.05% gel significantly outperformed Aldara® cream (containing 5% IMQ) formulation in terms of delivery efficiency to human skin (2.85 ± 0.74% vs 0.04 ± 0.01%). Despite IMQ being only partially incorporated in the micelles, the biodistribution profile showed that the optimized 0.05% gel delivered as much as 518.2 ± 173.3 ng/cm2 (1.04 ± 0.35% of the applied dose) to the viable epidermis and 236.4 ± 88.2 ng/cm2 (0.47 ± 0.18% of the applied dose) to the upper dermis where the target antigen presenting cells reside. In contrast, for Aldara® cream, the delivery efficiencies in those layers were less than 0.02%. The optimal 0.05% gel thus allowed therapeutically relevant drug levels to be achieved in target tissues despite a 100-fold dose reduction. Administration, Cutaneous Animals Biological Availability Drug Carriers/chemistry Drug Delivery Systems/methods Epidermis/metabolism Humans Imiquimod/administration & dosage/chemistry Micelles Nanoparticles/chemistry Polyethylene Glycols/chemistry Polymers/chemistry Skin/metabolism Skin Absorption/drug effects Swine Tissue Distribution Dewey 615 31 Section des sciences pharmaceutiques 17 false European Journal of Pharmaceutics and Biopharmaceutics 142 73ff80fd-6101-4910-904f-b1f8a42c1252 Article (Published version) Restricted 19_Lapteva_EJPB.pdf 1608854 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Self-assembled mPEG-hexPLA polymeric nanocarriers for the targeted cutaneous delivery of imiquimod	European Journal of Pharmaceutics and Biopharmaceutics			2019	340	2

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Mignot, Margaux