In Vitro Skin Retention and Drug Permeation through Intact and Microneedle Pretreated Skin after Application of Propranolol Loaded Microemulsions.
PURPOSE
Topical beta-blockers are efficacious for treating infantile hemangiomas, but no formulations have been specifically optimized for skin delivery. Our objective was to quantify skin concentrations and drug permeation of propranolol (a nonselective beta-blocker) after application of microemulsions to intact and microneedle pretreated skin.


METHODS
Four propranolol-loaded microemulsions were characterized for droplet size, surface charge, conductivity, pH, drug solubility, and drug release. Skin concentrations and drug permeation through skin were quantified using LC-MS. Skin-to-receiver ratios were used to compare the microemulsion formulations to a drug-in-PBS solution.


RESULTS
Propranolol solubility was significantly greater in microemulsions vs PBS. Cumulative drug release from the microemulsions over 24 h ranged from 13 to 26%. Skin concentrations and drug permeation through intact skin was significantly higher from PBS; however, the skin-to-receiver ratios were significantly higher for water-rich microemulsions compared to PBS or surfactant-rich microemulsions. Microneedle pretreatment significantly increased skin concentrations for all formulations. Skin-to-receiver ratios significantly increased after microneedle pretreatment for surfactant-rich microemulsions.


CONCLUSIONS
Microemulsion formulation can be altered to elicit different drug delivery profiles through MN-treated skin. This could be advantageous for maximizing local skin drug concentrations and improving dosing schedules for infantile hemangioma treatment.
['Kelchen|Megan N|MN|', 'Brogden|Nicole K|NK|http://orcid.org/0000-0001-6838-8847']
D000279:Administration, Cutaneous D000319:Adrenergic beta-Antagonists D000818:Animals D000959:Antihypertensive Agents D004337:Drug Carriers D016503:Drug Delivery Systems D065546:Drug Liberation D004655:Emulsions D006863:Hydrogen-Ion Concentration D009339:Needles D010316:Particle Size D011433:Propranolol D012867:Skin D012869:Skin Absorption D012995:Solubility D055672:Static Electricity D013552:Swine
skin microneedle propranolol microemulsion infantile hemangioma