title: Glycoside-based niosomal nanocarrier for enhanced in-vivo performance of Cefixime.
abstract: This study aimed to evaluate the potential of a novel glycoside non-ionic surfactant synthesized and characterized in our laboratory for increased oral bioavailability of Cefixime. The surfactant was synthesized by simple etherification of bergenin with bromoundecane and characterized by (1)H NMR and mass spectroscopy (MS). Biocompatibility of the surfactant (BRM-BG) was assessed by in-vitro cytotoxicity against NIH/3T3 cells and human blood hemolysis. In-vivo acute toxicity was evaluated in mices. Cefixime loaded BRM-BG niosomes were investigated for drug entrapment efficiency using HPLC and surface morphology and vesicle size by atomic force microscopy (AFM) and dynamic light scattering (DLS). The in-vivo oral bioavailability and pharmacokinetics studies were carried out using rabbits. Cefixime loaded BRM-BG vesicles were spherical in the size range of 178.66±8.17nm with a polydipersity index (PDI) of 0.20±0.01, offering an entrapment efficiency as high as 78.4±0.83%. When the surfactant was applied on NIH 3T3 tissue culture, as high as 90.77±3.15% and 86.86±3.02%, cell viability at 1000μg/mL concentration after 24 and 48h respectively were observed. The surfactant also caused 5.49±1.62% haemolysis and was found to be safe at a dose up to 2000mg/kg. In-vivo drug plasma concentration (Cmax) was found to be 9.69±1.22μg/mL, much higher than that resulting from the intake of commercial suspension and capsules. BRM-BG demonstrated to be safe and effective as carrier of Cefixime following oral dosing in rabbits. The BRM-BG surfactant delivery nano-system is relatively safe and in animal models it is an appropriate carrier for Cefixime, offering enhanced bioavailability compared to commercially available formulations of the drug.
authors.affiliation: Department of Pharmacy, University of Malakand, Khyber Pakhtoonkhwa 18000, Pakistan. Electronic address: imranbjr.khan@gmail.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Imran
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, Karachi University, Karachi 74200, Pakistan. Electronic address: raza.shah@iccs.edu.
authors.forename: Muhammad Raza
authors.initials: MR
authors.lastname: Shah
authors.affiliation: Department of Pharmacy, University of Malakand, Khyber Pakhtoonkhwa 18000, Pakistan. Electronic address: farhataziz80@hotmail.com.
authors.forename: Farhat
authors.initials: F
authors.lastname: Ullah
authors.affiliation: Department of Pharmacy, University of Malakand, Khyber Pakhtoonkhwa 18000, Pakistan. Electronic address: shafi_ullah34@yahoo.com.
authors.forename: Shafi
authors.initials: S
authors.lastname: Ullah
authors.affiliation: College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar. Electronic address: aelhissi@qu.edu.qa.
authors.forename: Abdelbary M A
authors.initials: AM
authors.lastname: Elhissi
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210000, Jiangsu, China. Electronic address: imwaqasnawaz@yahoo.com.
authors.forename: Waqas
authors.initials: W
authors.lastname: Nawaz
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, Karachi University, Karachi 74200, Pakistan. Electronic address: farids_ahmad@yahoo.com.
authors.forename: Farid
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacy, University of Malakand, Khyber Pakhtoonkhwa 18000, Pakistan. Electronic address: sadiquom@yahoo.com.
authors.forename: Abdul
authors.initials: A
authors.lastname: Sadiq
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, Karachi University, Karachi 74200, Pakistan. Electronic address: imdadchemist26@gmail.com.
authors.forename: Imdad
authors.initials: I
authors.lastname: Ali
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001578:Benzopyrans / Q000737:chemistry; D001682:Biological Availability; D020682:Cefixime / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D000067493:Dynamic Light Scattering / Q000379:methods; D005260:Female; D006027:Glycosides / Q000737:chemistry; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D018625:Microscopy, Atomic Force / Q000379:methods; D041681:NIH 3T3 Cells; D010316:Particle Size; D011817:Rabbits; D013501:Surface-Active Agents / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D001578:Benzopyrans; D004337:Drug Carriers; D006027:Glycosides; D008081:Liposomes; D013501:Surface-Active Agents; D020682:Cefixime; C006741:bergenin
keywords: Biocompatibility; Novel nonionic surfactant; Oral bioavailability; Vesicular drug carrier