title: In Vitro Evaluation of Novel Phenytoin-Loaded Alkyd Nanoemulsions Designed for Application in Topical Wound Healing.
abstract: Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity. Phenytoin-loaded alkyd nanoemulsions generally resulted in higher mean cell viability compared with equivalent concentration of phenytoin solutions, suggesting that the nanoemulsions provided a controlled-release property that maintained the optimum phenytoin level for keratinocyte growth. HaCaT cell proliferation, measured by 5-bromo-2-deoxyuridine uptake, was found to increase following exposure to increasing phenytoin concentration from 25 to 50 μg/mL in solution or encapsulated in nanoemulsions but declined at a drug concentration of 100 μg/mL. An in vitro cell monolayer wound scratch assay revealed that phenytoin solution or nanoemulsions producing 50 μg/mL phenytoin concentration resulted in 75%-82% "scratch closure" after 36 h, similar to medium containing 10% fetal bovine serum as a cell growth promoter. These findings indicate that phenytoin-loaded alkyd nanoemulsions show potential for promoting topical wound healing through enhanced proliferation of epidermal cells.
authors: School of Postgraduate Studies and Research, International Medical University, Kuala Lumpur, Malaysia.
authors: Siew Yong
authors: SY
authors: Teo
authors: Jeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia, Subang Jaya, Selangor, Malaysia.
authors: Mei Yeng
authors: MY
authors: Yew
authors: Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia; Colloids and Interface Science Centre (CISC), Centre of Excellence (COE), RRIM Sungai Buloh Research Station, Malaysian Rubber Board (MRB), Sungai Buloh, Selangor, Malaysia. Electronic address: leesiangyin@lgm.gov.my.
authors: Siang Yin
authors: SY
authors: Lee
authors: School of Postgraduate Studies and Research, International Medical University, Kuala Lumpur, Malaysia; ULTI Pharmaceuticals, Hamilton, New Zealand.
authors: Michael J
authors: MJ
authors: Rathbone
authors: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Seng Neon
authors: SN
authors: Gan
authors: Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
authors: Allan G A
authors: AGA
authors: Coombes
mesh_terms: D000287:Administration, Topical; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004655:Emulsions / Q000737:chemistry*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D009821:Oils / Q000737:chemistry*; D010672:Phenytoin / Q000008:administration & dosage* / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D004655:Emulsions; D009821:Oils; D010672:Phenytoin
keywords: alkyd nanoemulsion; phenytoin; topical; wound healing