Design and Optimization of Cationic Nanocapsules for Topical Delivery of Tretinoin: Application of the Box-Behnken Design, In Vitro Evaluation, and Ex Vivo Skin Deposition Study

Abstract

Cationic nanocapsules represent a promising approach for topical delivery purposes. We elaborated on a novel formulation based on the cationic nanocapsules to enhance the pharmacodynamic efficacy, user compliance, and photostability of tretinoin (TTN). To achieve this goal, TTN nanocapsules were prepared by the nanoprecipitation method. In order to statistically optimize formulation variables, a Box-Behnken design, using Design-Expert software, was employed. Three independent variables were evaluated: total weight of the cationic acrylic polymer ( X 1 ), oil volume ( X 2 ), and TTN amount ( X 3 ). The particle size and encapsulation efficiency percent (EE%) were selected as dependent variables. The optimal formulation demonstrated spherical morphology under scanning electron microscopy (SEM), optimum particle size of 116.3 nm, and high EE% of 83.2%. TTN-loaded nanocapsules improved photostability compared to its methanolic solution. The in vitro release study data showed that tretinoin was released in a sustained manner compared to the free drug. The ex vivo skin permeation study demonstrated that greater drug deposition into the epidermal region rather than the deep skin was observed with a gel containing TTN-loaded nanocapsules than that of drug solution, respectively. The skin irritation test revealed that the nanoencapsulation of the drug decreased its irritancy compared to the free drug. These results revealed the promising potential of cationic nanocapsules for topical delivery of tretinoin

Eco-Friendly Synthesis of Silver Nanoparticles by Nitrosalsola vermiculata to Promote Skin Wound Healing

“…Samples of 1 mL aliquots were withdrawn regularly and replaced by an equal volume of fresh buffer. The samples were then analyzed spectrophotometrically at λ max 396.46 nm for dissolved content quantification [30].…”

Use of Retinoids in Topical Antiaging Treatments: A Focused Review of Clinical Evidence for Conventional and Nanoformulations

“…In most studies, in vitro permeation studies and drug release tests were performed. Some authors have also performed in vivo skin irritation tests in rats [ 50 , 56 ] or rabbits [ 52 ] comparing the developed nanoformulations with conventional formulations containing tretinoin. Overall, prolonged release of the active ingredient, improved stability, and reduced irritation were achieved.…”

Lipo-polymeric nano-complexes for dermal delivery of a model protein

“…Increased drug deposition in the epidermis, reduced skin irritation, and higher photostability were all seen in TTN-loaded nanocapsules. 11 In contrast, cationic nanocarriers, especially cationic polymers, have shown encouraging outcomes in drug delivery despite these drawbacks, further can be complexed with proteins and peptides, resulting in enhancing their stability and bioavailability. [10][11][12] The lack of stability and bioavailability of proteins and peptides, despite their importance as therapeutic agents, severely restricts their utilization.…”

“…11 In contrast, cationic nanocarriers, especially cationic polymers, have shown encouraging outcomes in drug delivery despite these drawbacks, further can be complexed with proteins and peptides, resulting in enhancing their stability and bioavailability. [10][11][12] The lack of stability and bioavailability of proteins and peptides, despite their importance as therapeutic agents, severely restricts their utilization. 13 To prevent breakdown and facilitate transport across cell membranes, proteins and peptides may be complexed with cationic polymers.…”