title: Design, synthesis and ex-vivo release studies of colon-specific polyphosphazene-anticancer drug conjugates.
abstract: Colon-specific azo based polyphosphazene-anticancer drug conjugates (11-18) have been synthesized and evaluated by ex-vivo release studies. The prepared polyphosphazene drug conjugates (11-18) are stable in acidic (pH=1.2) buffer which showed that these polymer drug conjugates are protected from acidic environment which is the primary requirement of colon specific targeted drug delivery. The ex-vivo release profiles of polyphosphazene drug conjugates (11-18) have been performed in the presence as well as in the absence of rat cecal content. The results showed that more than 89% of parent drugs (methotrexate and gemcitabine) are released from polymeric backbone of polyphosphazene drug conjugates (14 and 18) having n-butanol (lipophilic moiety). The in-vitro cytotoxicity assay has also been performed which clearly indicated that these polymeric drug conjugates are active against human colorectal cancer cell lines (HT-29 and COLO 320 DM). The drug release kinetic study demonstrated that Higuchi's equation is found to be best fitted equation which showed that release of drug from polymeric backbone as square root of time dependent process based on non-fickian diffusion. Therefore, the synthesized polyphosphazene azo based drug conjugates of methotrexate and gemcitabine are the potential candidates for colon targeted drug delivery system with minimal undesirable side effects.
authors.affiliation: Polymer Chemistry and Technology Research Laboratory, Department of Pharmaceutical Chemistry, Indo-Soviet Friendship (I.S.F), College of Pharmacy, Ferozepur Road, Moga 142 001, India; Research Scholar, Uttarakhand Technical University, Dehradun 248 007, India. Electronic address: drrajiv81@yahoo.in.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Polymer Chemistry and Technology Research Laboratory, Department of Pharmaceutical Chemistry, Indo-Soviet Friendship (I.S.F), College of Pharmacy, Ferozepur Road, Moga 142 001, India; The University of Georgia, College of Pharmacy, GA 30602, USA.
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Rawal
authors.affiliation: Polymer Chemistry and Technology Research Laboratory, Department of Pharmaceutical Chemistry, Indo-Soviet Friendship (I.S.F), College of Pharmacy, Ferozepur Road, Moga 142 001, India.
authors.forename: Manav
authors.initials: M
authors.lastname: Malhotra
authors.affiliation: School of Pharmacy, Asmara College of Health Sciences, Asmara, Eritrea.
authors.forename: A K
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Polymer Chemistry and Technology Research Laboratory, Department of Pharmaceutical Chemistry, Indo-Soviet Friendship (I.S.F), College of Pharmacy, Ferozepur Road, Moga 142 001, India.
authors.forename: T R
authors.initials: TR
authors.lastname: Bhardwaj
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003106:Colon; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008727:Methotrexate / Q000737:chemistry / Q000493:pharmacokinetics; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009943:Organophosphorus Compounds; D011108:Polymers; C108974:poly(phosphazene); D003841:Deoxycytidine; D008727:Methotrexate; D000093542:Gemcitabine
keywords: Azoreductase; Colon-specific; Gemcitabine; Methotrexate; Polyphosphazene