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Ion Pair Strategy in Solid Lipid Nanoparticles: a Targeted Approach to Improve Epidermal Targeting with Controlled Adapalene Release, Resulting Reduced Skin Irritation

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Abstract

Purpose

Adapalene (AD) is one of the main retinoids used in the topical therapy of acne, an extremely common skin disease usually associated with psychological morbidity. However, like other retinoids, AD is frequently associated with skin irritation. To overcome the skin irritation, we proposed the encapsulation of AD in solid lipid nanoparticles (SLNs) using the ion pair strategy.

Methods

The developed SLN-AD was characterized by high-performance liquid chromatography, differential scanning calorimetry, X-ray diffraction, synchrotron small-angle X-ray scattering, and transmission electron microscopy. In vitro permeation tests using porcine skin and in vivo mice skin irritation test were performed to evaluate, respectively, the drug’s skin distribution and the skin irritation.

Results

The characterization studies were able to demonstrate that the proposed strategy effectively provided high AD encapsulation in SLNs and its incorporation into a hydrophilic gel. Sustained release, epidermal targeting, and less skin irritation were observed for SLN-AD gel in comparison to the marketed AD gel.

Conclusions

The studies demonstrated that the encapsulation of AD in SLNs through the formation of an ion pair is a valuable alternative to diminish the adverse skin reactions caused by AD and can optimize patient adherence to treatment.

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Abbreviations

AD:

Adapalene

DC-Chol® :

3β-[N-(Dimethylaminoethane)carbamoyl] cholesterol

DSC:

Differential scanning calorimetry

EE:

Encapsulation efficiency

FTIR:

Fourier-transform infrared spectroscopy

HPLC:

High performance liquid chromatography

MH:

Maprotiline hydrochloride

PBS:

Phosphate-buffered saline

PDI:

Polydispersity index

PU:

Pilosebaceous unit

RA:

All-trans retinoic acid

SA:

Stearylamine

SAXS:

Synchrotron Small Angle X-ray Scattering

SLN:

Solid lipid nanoparticles

TEM:

Transmission electron microscopy

XRD:

X-ray diffraction

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Campus Pampulha – Universidade Federal de Minas Gerais (UFMG), Av Antônio Carlos, 662, Belo Horizonte, MG, CEP 31270-901, Brazil

    Linna B. O. Rodrigues, Flávia A. Lima, Camila P. B. Alves, Marta M. G. Aguiar, Lucas A. M. Ferreira & Gisele A. C. Goulart

  2. Department of Morphology, Institute of Biological Sciences, UFMG, Belo Horizonte, MG, CEP 31270-901, Brazil

    Elisângela Martins-Santos & Cleida A. Oliveira

  3. Department of Metallurgical and Materials Engineering, UFMG, Belo Horizonte, MG, CEP 31270-901, Brazil

    Rodrigo L. Oréfice

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  1. Linna B. O. Rodrigues
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  2. Flávia A. Lima
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  3. Camila P. B. Alves
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Correspondence to Gisele A. C. Goulart.

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Rodrigues, L.B.O., Lima, F.A., Alves, C.P.B. et al. Ion Pair Strategy in Solid Lipid Nanoparticles: a Targeted Approach to Improve Epidermal Targeting with Controlled Adapalene Release, Resulting Reduced Skin Irritation. Pharm Res 37, 148 (2020). https://doi.org/10.1007/s11095-020-02866-0

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