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Liposomes for targeting hepatocellular carcinoma: use of conjugated arabinogalactan as targeting ligand.
Shah, Sanket M; Goel, Peeyush N; Jain, Ankitkumar S; Pathak, Pankaj O; Padhye, Sameer G; Govindarajan, Srinath; Ghosh, Sandipto S; Chaudhari, Pradip R; Gude, Rajiv P; Gopal, Vijaya; Nagarsenker, Mangal S.
Affiliation
  • Shah SM; Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai-400098, India.
  • Goel PN; Tata Memorial Centre, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai 410210, India.
  • Jain AS; Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai-400098, India.
  • Pathak PO; Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai-400098, India.
  • Padhye SG; Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai-400098, India.
  • Govindarajan S; Council of Scientific and Industrial Research-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500007, India.
  • Ghosh SS; Small Animal Imaging Facility (SAIF), Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Kharghar, Mumbai 410210, India.
  • Chaudhari PR; Small Animal Imaging Facility (SAIF), Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Kharghar, Mumbai 410210, India.
  • Gude RP; Tata Memorial Centre, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai 410210, India.
  • Gopal V; Council of Scientific and Industrial Research-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500007, India.
  • Nagarsenker MS; Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai-400098, India. Electronic address: mangal.nagarsenker@gmail.com.
Int J Pharm ; 477(1-2): 128-39, 2014 Dec 30.
Article in En | MEDLINE | ID: mdl-25311181
Present study investigates the potential of chemically modified (Shah et al., 2013) palmitoylated arabinogalactan (PAG) in guiding liposomal delivery system and targeting asialoglycoprotein receptors (ASGPR) which are expressed in hepatocellular carcinoma (HCC). PAG was incorporated in liposomes during preparation and doxorubicin hydrochloride was actively loaded in preformed liposomes with and without PAG. The liposomal systems with or without PAG were evaluated for in vitro release, in vitro cytotoxicity, in vitro cell uptake on ASGPR(+) cells, in vivo pharmacokinetic study, in vivo biodistribution study, and in vivo efficacy study in immunocompromised mice. The particle size for all the liposomal systems was below 200 nm with a negative zeta potential. Doxorubicin loaded PAG liposomes released significantly higher amount of doxorubicin at pH 5.5 as compared to pH 7.4, providing advantage for targeted tumor therapy. Doxorubicin in PAG liposomes showed superior cytotoxicity on ASGPR(+) HepG2 cells as compared to ASGPR(-), MCF7, A549, and HT29 cells. Superior uptake of doxorubicin loaded PAG liposomes as compared to doxorubicin loaded conventional liposomes was evident in confocal microscopy studies. Higher AUC in pharmacokinetic study and higher deposition in liver was observed for PAG liposomes compared to conventional liposomes. Significantly higher tumor suppression was noted in immunocompromised mice for mice treated with PAG liposomes as compared to the conventional liposomes. Targeting ability and superior activity of PAG liposomes is established pre-clinically suggesting potential of targeted delivery system for improved treatment of HCC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Doxorubicin / Carcinoma, Hepatocellular / Galactans / Liver Neoplasms Limits: Animals / Female / Humans / Male Language: En Journal: Int J Pharm Year: 2014 Document type: Article Affiliation country: India Country of publication: Netherlands

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Doxorubicin / Carcinoma, Hepatocellular / Galactans / Liver Neoplasms Limits: Animals / Female / Humans / Male Language: En Journal: Int J Pharm Year: 2014 Document type: Article Affiliation country: India Country of publication: Netherlands