Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: An ex vivo and in vivo study using an NC/Nga mouse model

• Published in: International journal of pharmaceutics 2013-02, Vol.444 (1-2), p.109-119
• Main Authors: Hussain, Zahid, Katas, Haliza, Mohd Amin, Mohd Cairul Iqbal, Kumolosasi, Endang, Buang, Fhataheya, Sahudin, Shariza
• Format: Article
• Language: English
• Subjects: adverse effects; Allergic contact dermatitis; animal models; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - chemistry; antioxidants; atopic dermatitis; chitosan; Chitosan - chemistry; Corticosteroid; cortisol; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - metabolism; Dermatitis, Atopic - pathology; Dinitrofluorobenzene; Disease Models, Animal; Drug Carriers - administration & dosage; Drug Carriers - chemistry; erythema; Hydrocortisone - administration & dosage; Hydrocortisone - chemistry; in vivo studies; Mice; nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Phenylethyl Alcohol - administration & dosage; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - chemistry; Polymeric nanoparticles; Polyphenol; Skin - metabolism; Skin Absorption; Topical co-delivery; zeta potential
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.01.024

In this study, hydroxytyrosol (HT; a potent antioxidant) was co-administered with hydrocortisone (HC) to mitigate the systemic adverse effects of the latter and to provide additional anti-inflammatory and antioxidant benefits in the treatment of atopic dermatitis (AD). The co-loaded nanoparticles (NPs) prepared had shown different particle sizes, zeta potentials, loading efficiencies, and morphology, when the pH of the chitosan solution was increased from 3.0 to 7.0. Ex vivo permeation data showed that the co-loaded NPs formulation significantly reduced the corresponding flux (17.04μg/cm2/h) and permeation coefficient (3.4×10−3cm/h) of HC across full-thickness NC/Nga mouse skin. In addition, the NPs formulation showed higher epidermal (1560±31μg/g of skin) and dermal (880±28μg/g of skin) accumulation of HC than did a commercial HC formulation. Moreover, an in vivo study using an NC/Nga mouse model revealed that compared to the other treatment groups, the group treated with the NPs formulation efficiently controlled transepidermal water loss (13±2g/m2/h), intensity of erythema (207±12), and dermatitis index (mild). In conclusion, NPs co-loaded with HC/HT is proposed as a promising system for the percutaneous co-delivery of anti-inflammatory and antioxidative agents in the treatment of AD.