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Pharmaceutics. 2021 Nov 26;13(12). doi: 10.3390/pharmaceutics13122016.

Transdermal Drug Delivery in the Pig Skin.

Pharmaceutics

Ignacio Ordiz, José A Vega, Raquel Martín-Sanz, Olivia García-Suárez, Miguel E Del Valle, Jorge Feito

Affiliations

  1. Departamento de Morfología y Biología Celular, Universidad de Oviedo, 33006 Oviedo, Spain.
  2. Grupo SINPOS, Universidad de Oviedo, 33006 Oviedo, Spain.
  3. Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Providencia, 7500912 Santiago de Chile, Chile.
  4. Servicio de Oftalmología, Complejo Asistencial Universitario de Salamanca, 37007 Salamanca, Spain.
  5. Servicio de Anatomía Patológica, Complejo Hospitalario Universitario de Salamanca, 37007 Salamanca, Spain.

PMID: 34959299 PMCID: PMC8707795 DOI: 10.3390/pharmaceutics13122016

Abstract

Transdermal delivery can be accomplished through various mechanisms including formulation optimization, epidermal stratum corneum barrier disruption, or directly by removing the stratum corneum layer. Microneedling, electroporation, a combination of both and also the intradermal injection known as mesotherapy have proved efficacy in epidermal-barrier disruption. Here we analyzed the effects of these methods of epidermal-barrier disruption in the structure of the skin and the absorption of four compounds with different characteristics and properties (ketoprofen, biotin, caffein, and procaine). Swine skin (Pietrain x Durox) was used as a human analogue, both having similar structure and pharmacological release. They were biopsied at different intervals, up to 2 weeks after application. High-pressure liquid chromatography and brightfield microscopy were performed, conducting a biometric analysis and measuring histological structure and vascular status. The performed experiments led to different results in the function of the studied molecules: ketoprofen and biotin had the best concentrations with intradermal injections, while delivery methods for obtaining procaine and caffein maximum concentrations changed on the basis of the lapsed time. The studied techniques did not produce significant histological alterations after their application, except for an observed increase in Langerhans cells and melanocytes after applying electroporation, and an epidermal thinning after using microneedles, with variable results regarding dermal thickness. Although all the studied barrier disruptors can accomplish transdermal delivery, the best disruptor is dependent on the particular molecule.

Keywords: electroporation; intradermal injection; mesotherapy; microneedling; morphology; skin; transdermal delivery

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