title: In-vivo dermal pharmacokinetics, efficacy, and safety of skin targeting nanoparticles for corticosteroid treatment of atopic dermatitis.
abstract: The objective of this study was to investigate the in-vivo behavior of topically applied cationic polymeric chitosan nanoparticles (CSNPs) loaded with anti-inflammatory (hydrocortisone, HC) and antimicrobial (hydroxytyrosol, HT) drugs, to elucidate their skin targeting potential for the treatment of atopic dermatitis (AD). Compared to the commercial formulation, the HC-HT loaded CSNPs showed significantly improved drug penetration into the epidermal and dermal layers of albino Wistar rat skin without saturation. Dermal pharmacokinetic of CSNPs with a size of 228.5±7nm and +39±5mV charges revealed that they penetrated 2.46-fold deeper than the commercial formulation did, and had greater affinity at the skin target site without spreading to the surrounding tissues, thereby providing substantial safety benefits. In repeated dermal application toxicity studies, the HC-HT CSNPs showed no evidence of toxicity compared to the commercial formulation, which induced skin atrophy and higher liver enzyme levels. In conclusion, the positively charged HC-HT CSNP formulation exhibited promising local delivery and virtually no treatment-related toxicities, suggesting it may be an efficient and viable alternative for commercially available AD treatments.
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz 50300, Kuala Lumpur, Malaysia.
authors.forename: Muhammad Irfan
authors.initials: MI
authors.lastname: Siddique
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz 50300, Kuala Lumpur, Malaysia. Electronic address: haliza.katas@ukm.edu.my.
authors.forename: Haliza
authors.initials: H
authors.lastname: Katas
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz 50300, Kuala Lumpur, Malaysia.
authors.forename: Mohd Cairul Iqbal Mohd
authors.initials: MC
authors.lastname: Amin
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz 50300, Kuala Lumpur, Malaysia.
authors.forename: Shiow-Fern
authors.initials: SF
authors.lastname: Ng
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz 50300, Kuala Lumpur, Malaysia.
authors.forename: Mohd Hanif
authors.initials: MH
authors.lastname: Zulfakar
authors.affiliation: Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
authors.forename: Adawiyah
authors.initials: A
authors.lastname: Jamil
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000009:adverse effects; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D000893:Anti-Inflammatory Agents; C005975:3,4-dihydroxyphenylethanol; D048271:Chitosan; D010626:Phenylethyl Alcohol; D006854:Hydrocortisone
keywords: Antimicrobial activity; Chitosan; Dermal pharmacokinetics; Polymeric nanoparticles; Safety; Skin disease; Topical glucocorticoids