Enhancement of Skin Delivery of Drugs Using Proposome Depends on Drug Lipophilicity

Abstract

The study aims to investigate the propylene glycol-based liposomes named ‘proposomes’ in enhancing skin permeation of drugs with different physicochemical properties. Ibuprofen, tofacitinib citrate, rhodamine B, and lidocaine were loaded into proposomes. These drug formulations were analyzed for particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro skin permeation. The confocal laser scanning microscopy was performed on skin treated with calcein and rhodamine B laden proposomes. The transdermal delivery relative to physicochemical properties of drugs such as logP, melting point, molecular weight, solubility, etc., were analyzed. We tested the safety of the proposomes using reconstructed human skin tissue equivalents, which were fabricated in-house. We also used human cadaver skin samples as a control. The proposomes had an average diameter of 128 to 148 nm. The drug’s entrapment efficiencies were in the range of 42.9–52.7%, translating into the significant enhancement of drug permeation through the skin. The enhancement ratio was 1.4 to 4.0, and linearly correlated to logP, molecular weight, and melting point. Confocal imaging also showed higher skin permeation of calcein and rhodamine B in proposome than in solution. The proposome was found safe for skin application. The enhancement of skin delivery of drugs through proposomes was dependent on the lipophilicity of the drug. The entrapment efficiency was positively correlated with logP of the drug, which led to high drug absorption.

Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

“…High lipophilicity promotes the nonspecific binding of drug molecules with plasma proteins, thus contributing to the reduced penetration of these compounds through the BBB. The literature data indicate that compounds with a moderate lipophilicity oscillating around 2 show optimal abilities to reach molecular targets [ 13 , 14 , 15 ].…”

Prediction of drug permeation through microneedled skin by machine learning

“…To build the machine learning models, seven features were selected for MLR, RF, and XGBoost, including the skin type (rat and human), type of the MN (hydrogel and plastic), MN length, surface area of the MN, drug loading in MN, drug permeation time, and the MW of the drug. Skin type, 9 drug permeation time, 33 and drug MW 42 are found affecting drug permeation through skin in our previous studies on non-MN facilitated transdermal drug delivery. The type of MN, MN length, surface area of MN, and drug loading in MN are potentially important parameters we identified for MNfacilitated transdermal drug delivery, hence included in the models in the current study.…”

Naringin: Nanotechnological Strategies for Potential Pharmaceutical Applications

“…In general, proposomes are used for the epidermal, dermal, and transdermal delivery of skin drugs and other therapeutic applications by varying their lipid and PG composition [ 55 , 56 ]. Like ethanol in ethosomes, PG is added to improve drug and formulation stability, which has as a result enhanced penetration and drug deposition on the skin.…”