title: Fractional Laser Ablation for the Cutaneous Delivery of Triamcinolone Acetonide from Cryomilled Polymeric Microparticles: Creating Intraepidermal Drug Depots.
abstract: The efficacy of some dermatological therapies might be improved by the use of "high dose" intraepidermal drug reservoir systems that enable sustained and targeted local drug delivery, e.g., in the treatment of keloids and hypertrophic scars. Here, a fractionally ablative erbium:YAG laser was used to enable "needle-less" cutaneous deposition of polymeric microparticles containing triamcinolone acetonide (TA). The microparticles were prepared using a freeze-fracture technique employing cryomilling that resulted in drug loading efficiencies of ∼100%. They were characterized by several different techniques, including scanning electron microscopy, powder X-ray diffraction and differential scanning calorimetry. TA was quantified by validated HPLC-UV and UHPLC-MS/MS analytical methods. In vitro release studies demonstrated the effect of polymer properties on TA release kinetics. Confocal laser scanning microscopy enabled visualization of cryomilled microparticles containing fluorescein and Nile Red in the cutaneous micropores and the subsequent release of fluorescein into the micropores and its diffusion throughout the epidermis and upper dermis. The biodistribution of TA, i.e. the amount of drug as a function of depth in skin, following microparticle application was much more uniform than with a TA suspension and delivery was selective for deposition with less transdermal permeation. These findings suggest that this approach may provide an effective, targeted and minimally invasive alternative to painful intralesional injections for the treatment of keloid scars.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva & University of Lausanne , 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland.
authors.forename: Mayank
authors.initials: M
authors.lastname: Singhal
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva & University of Lausanne , 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland.
authors.forename: Sergio
authors.initials: S
authors.lastname: Del Río-Sancho
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva & University of Lausanne , 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland.
authors.forename: Kiran
authors.initials: K
authors.lastname: Sonaje
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva & University of Lausanne , 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland.
authors.forename: Yogeshvar N
authors.initials: YN
authors.lastname: Kalia
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D016503:Drug Delivery Systems; D053685:Laser Therapy; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012867:Skin / Q000187:drug effects*; D013552:Swine; D014222:Triamcinolone Acetonide / Q000008:administration & dosage*
chemical_list: D000893:Anti-Inflammatory Agents; D011108:Polymers; D014222:Triamcinolone Acetonide
keywords: cryomilling; fractional laser ablation; keloid; microparticle; skin