Development and Characterization of a Topical Gel Formulation of Adapalene-TyroSpheres and Assessment of Its Clinical Efficacy

Abstract

In this study we aimed to develop a semi-solid formulation of polymeric nanoparticles loaded with adapalene to enhance the efficacy and improve the skin tolerability in acne therapy. An amphiphilic and biocompatible copolymer that self-assembles to nanospheres (known as TyroSpheres) was used to encapsulate adapalene and increase its solubility. A water-soluble viscous agent was applied to prepare a gel formulation of adapalene-loaded TyroSpheres (aapalene-TyroSphere). Particle size, morphology, homogeneity, and rheological characteristics of the adapalene-TyroSphere gel formulations were studied. The formulation with the preferred physical and structural properties was further investigated for in vitro skin irritation and in vivo comedolytic activity in a rhino mouse model. Based on the in vitro skin irritation study encapsulation of adapalene in TyroSphere significantly decreased secretion of pro-inflammatory cytokines (IL-1α and IL-8), confirming that the TyroSphere formulation of adapalene is less irritant than the commercial gel (Differin). TyroSphere gel formulation of adapalene improved the comedolytic properties of the formulation by significantly reducing the size of open utricles in rhino mice compared to Differin treatment. Using TyroSpheres, we were able to develop an alternative topical formulation of adapalene, which is potentially less irritant and more potent than the commercial product.

Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation

“…From the other experiments, as mentioned in Sections 3.3-3.5, the selected colloidal dispersion was NLC, so the gel formulation containing the chili extract-loaded NLC with 0.075% capsaicin was our sample of interest. The percentages of EpiDerm TM cell viability after exposure to samples and controls were over 50%, indicating that all formulations were non-irritant [25,26], compared with 5% SDS (positive control), which showed strong irritancy. However, the percentage of cell viability from Gel NLC_C (91.85% ± 0.16%) was significantly (p < 0.05) higher than that of chili extract gel (86.49% ± 4.34%), revealing that the skin irritation of NLC was lower than the free form alternative, similar to the findings of previous reports [10,25].…”

“…From the other experiments, as mentioned in Sections 3.3 to 3.5, 545 the selected colloidal dispersion was NLC, so the gel formulation containing the chili extract-loaded 546 NLC with 0.075% capsaicin was our sample of interest. The percentages of EpiDerm TM cell viability 547 after exposure to samples and controls were over 50%, indicating that all formulations were non-548 irritant [25,26], compared with 5% SDS (positive control), which showed strong irritancy. However,…”

“…The OD values were determined using a spectrophotometer at 570 nm. The percent cell viability was calculated using Equation 9 [25,26].…”

“…The release of IL-1α after a 24-h incubation period with the test samples from the EpiDerm RHE tissue to the culture medium was collected and quantified using Quantikine ® ELISA kits according to the assay protocol provided by the manufacturer. UV-visible spectrophotometric measurements were performed at 450 nm using a microplate reader (Biotek Power Wave X, VT, USA) [25,26].…”

Advanced development of a non-ionic surfactant and cholesterol material based niosomal gel formulation for the topical delivery of anti-acne drugs

“…ADP showed poor therapeutic applications clinically because it causes irritation of the skin, dryness, a burning or stinging sensation, peeling/ exfoliation and photosensitivity with pigmentation. To overcome these limitations, various approaches have been studied such as liposomes, 5 TyroSpheres, 6 polymeric micelles 7 and hydrogel matrices 8 to control and improve the ADP permeation. Nanovesicles have shown huge potential in topical delivery due to their advantages such as prolonged therapeutic effect and avoidance of the entry of the drug into the systemic circulation, thereby controlling the side effects.…”