title: Pharmacodynamic study of eprosartan mesylate-loaded transfersomes Carbopol®gel under Dermaroller®on rats with methyl prednisolone acetate-induced hypertension.
abstract: The objective of present study was to prepare eprosartan mesylate (EM)-loaded transfersomes Carbopol®gel and characterized for various parameters, including in vitro skin permeation, in vivo antihypertensive study, skin irritation, and histological study. Furthermore, effect of transfersomes gel on angiotensin II type-1 receptor (AT1R) mRNA and protein expressions on smooth vascular muscles of aorta was determined by real-time polymerase chain reaction (RT-PCR) and western blot analysis. The physical evaluation parameters were detected to be in correspondence with reference marketed gel formulation. The transdermal flux, permeability coefficient, and Tlagof EM from transfersomes gel were found to be 26.76 ± 1.66μg/cm2/h, 8.93 ± 0.55 ×10-3cm/h, and 2.17 ± 0.29h, respectively, across rat skin pretreated with microneedle (Dermaroller®). Pharmacodynamic study showed prolonged and better management of hypertension after the application of transfersomes gel in experimentally induced hypertensive Wistar rats as compared with oral control formulation. The in vivo angiotensin II type-1 blocking efficacy of prepared transfersomes gel and control formulation was also supported with RT-PCR and western blot analysis of AT1R mRNA and protein expressions on smooth vascular muscles of aorta. Skin irritation and skin histological assessment showed that the prepared transfersomes Carbopol®gel was safe to be used for transdermal route. It is concluded that the incorporation of transfersomes into gel formulation offered enhanced skin contact, ease of application, and found to be a suitable drug reservoir for the transdermal delivery of EM for the management of hypertension in Wistar rats.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: abdulahad20@yahoo.com.
authors.forename: Abdul
authors.initials: A
authors.lastname: Ahad
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulmohsen A
authors.initials: AA
authors.lastname: Al-Saleh
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Al-Mohizea
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Fahad I
authors.initials: FI
authors.lastname: Al-Jenoobi
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Raish
authors.affiliation: Pharmaceutical Sciences Department, College of Pharmacy-3163, King Saud bin Abdulaziz University for Health Sciences, and King Abdullah International Medical Research Center, Ministry of National Guard, Health Affairs, Riyadh 11426, Saudi Arabia.
authors.forename: Alaa Eldeen B
authors.initials: AEB
authors.lastname: Yassin
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Mohd Aftab
authors.initials: MA
authors.lastname: Alam
mesh_terms: D000179:Acrylates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000180:Acrylic Resins; D000279:Administration, Cutaneous; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005782:Gels; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007509:Irritants / Q000633:toxicity; D008775:Methylprednisolone / Q000031:analogs & derivatives; D000077555:Methylprednisolone Acetate; D009339:Needles; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000473:pathology; D012869:Skin Absorption; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000179:Acrylates; D000180:Acrylic Resins; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D004337:Drug Carriers; D005782:Gels; D007093:Imidazoles; D007509:Irritants; D013876:Thiophenes; C006912:carboxypolymethylene; C068373:eprosartan; D000077555:Methylprednisolone Acetate; D008775:Methylprednisolone
keywords: Antihypertensive activity; Carbopol(®) gel; Eprosartan mesylate; Skin irritation; Transfersomes; Western blot