Research Article: Adapalene-loaded poly(ε-caprolactone) microparticles: Physicochemical characterization and in vitro penetration by photoacoustic spectroscopy

Date Published: March 21, 2019

Publisher: Public Library of Science

Author(s): Jessica Mendes Nadal, Guilherme dos Anjos Camargo, Andressa Novatski, William Roger Macenhan, Daniele Toniolo Dias, Fernanda Malaquias Barboza, Amanda Lyra, João Ricardo Roik, Josiane Padilha de Paula, Aloisi Somer, Paulo Vitor Farago, Thomas Webster.


Adapalene (ADAP) is an important drug widely used in the topical treatment of acne. It is a third-generation retinoid and provides keratolytic, anti-inflammatory, and antiseborrhoic action. However, some topical adverse effects such as erythema, dryness, and scaling have been reported with its commercial formula. In this sense, the microencapsulation of this drug using polyesters can circumvent its topical side effects and can lead to the enhancement of drug delivery into sebaceous glands. The goal of this work was to obtain ADAP-loaded poly(ε-caprolactone) (PCL) microparticles prepared by a simple emulsion/solvent evaporation method. Formulations containing 10 and 20% of ADAP were successfully obtained and characterized by morphological, spectroscopic, and thermal studies. Microparticles presented encapsulation efficiency of ADAP above 98% and showed a smooth surface and spherical shape. Fourier transform infrared spectroscopy (FTIR) results presented no drug-polymer chemical bond, and a differential scanning calorimetry (DSC) technique showed a partial amorphization of the drug. ADAP permeation in the Strat-M membrane for transdermal diffusion testing was evaluated by photoacoustic spectroscopy (PAS) in the spectral region between 225 and 400 nm after 15 min and 3 h from the application of ADAP-loaded PCL formulations. PAS was successfully used for investigating the penetration of polymeric microparticles. In addition, microencapsulation decreased the in vitro transmembrane diffusion of ADAP.

Partial Text

Adapalene (ADAP; C28H28O3; MW: 412.52 g.mol-1) or 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthalene-2-carboxylic acid (Fig 1) is a synthetic analog of retinol (vitamin A) used for the acne treatment [1,2]. The mechanism of action of ADAP is due to the selective interaction by specific retinoid intranuclear receptors (RARs), leading to the reduction of sebum production by sebaceous glands, reversing inflammatory lesions, follicular hyperkeratinization and the microcomedones formation [3–6]. The mechanism of action of ADAP also decreases the expression of the toll-like receptors 2 (TLR2) used by the Propionibacterium acnes, inhibiting the release of pro-inflammatory cytokines [4,5,7,8]. In addition, the modulation of the immune response occurs by altering the expression of CD1-d and IL10, causing an increase in the antimicrobial activity of the immune system [9–11]. During the early course of ADAP treatment, some local adverse events can be noticed such as: erythema, dryness, peeling, burning, and itching. To minimize these side effects, users need to decrease exposure to sunlight, avoid extreme temperatures, and use moisturizers [12].

ADAP-loaded PCL microparticles were effectively prepared by a simple emulsion/solvent evaporation method. Micrometer-sized formulations with high drug-loading efficiencies were obtained. No changes in FTIR assignments were recorded after the microencapsulation procedure. In addition, the photoacoustic spectroscopy showed that the microencapsulation decreased the in vitro transmembrane diffusion of ADAP, highlighting the particular characteristic of this technique to estimate the permeation of drugs through synthetic membranes. In summary, these formulations can be used in further innovative skin products intended for treating acne.