title: Effect of fluidizing agents on paclitaxel penetration in cervical cancerous monolayer membranes.
abstract: The aim of this study was to compare modulation of paclitaxel penetration in cancerous and normal cervical monolayers by four fluidizing agents: PCPG (9:1 DPPC:PG), PCPE (9:1 DPPC:DOPE), ALEC (7:3 DPPC:PG) and Exosurf (13.5:1.5:1.0 DPPC:hexadecanol:tyloxapol). Presence of the fluidizing agents improved drug penetration significantly. PCPG and PCPE were promising penetration enhancers. PCPG 0.1% caused 3.8- and 1.7-fold higher maximum increments in surface pressure due to drug penetration, (Delta pi)(max), than the control in cancerous and normal monolayers, respectively, at 20 mN/m. In cancerous monolayer at 20 mN/m, presence of 0.1%, 0.5%, 1%, 5% and 10% PCPE produced 3.4-, 5.7-, 7.4-, 9.6- and 9.8-fold higher drug penetration compared to the control monolayer without PCPE, respectively. In cancerous monolayer at 20 mN/m, PCPG and PCPE liposomes having 1 mg lipid gave 2.1 and 3.6 times higher (Delta pi)(max )compared to the control, respectively. Further, the liposomal drug penetration was found to be directly proportional to the liposomal lipid content. The effect of the fluidizing agents was confirmed by increased calcein release from model cervical cancer liposomes. These results may have implications in using the above biocompatible lipids and surfactants as penetration enhancers along with anticancer drugs or as carriers for liposomal formulations of anticancer drugs for improved membrane penetration.
authors: School of Biosciences and Bioengineering, Indian Institute of Technology, Mumbai, 400076, India.
authors: A
authors: A
authors: Preetha
authors: N
authors: N
authors: Huilgol
authors: R
authors: R
authors: Banerjee
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000494:pharmacology; D005260:Female; D005452:Fluoresceins / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008560:Membrane Fluidity / Q000187:drug effects*; D008567:Membranes, Artificial; D008954:Models, Biological; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010743:Phospholipids / Q000494:pharmacology; D010767:Phosphorylcholine / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D005233:Fatty Alcohols; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D008567:Membranes, Artificial; D010743:Phospholipids; D013501:Surface-Active Agents; C068829:artificial lung expanding compound; D010767:Phosphorylcholine; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; D017239:Paclitaxel; C007740:fluorexon
references: J Cancer Res Ther. 2005 Jul-Sep;1(3):180-6
references: 17998650
references: Eur J Pharm Biopharm. 2005 Jan;59(1):177-87
references: 15567316
references: J Control Release. 2002 Oct 4;83(2):273-286
references: 12363453
references: J Colloid Interface Sci. 2004 Jun 1;274(1):55-68
references: 15120278
references: Biomaterials. 2003 Dec;24(27):5037-44
references: 14559017
references: FEBS Lett. 1991 Apr 9;281(1-2):133-6
references: 1707829
references: J Control Release. 2000 Jul 3;67(2-3):395-408
references: 10825570
references: J Control Release. 2000 Jan 3;63(1-2):19-30
references: 10640577
references: J Control Release. 2001 Mar 12;71(1):53-69
references: 11245908
references: Colloids Surf B Biointerfaces. 2006 Dec 1;53(2):179-86
references: 17046216
references: Pulm Pharmacol Ther. 2001;14 (2):85-91
references: 11273788
references: Int J Pharm. 2002 Mar 20;235(1-2):179-92
references: 11879753
references: Gynecol Oncol. 2004 Jan;92(1):59-63
references: 14751139
references: Int J Pharm. 2005 Apr 27;294(1-2):149-55
references: 15814239
references: Adv Drug Deliv Rev. 2004 Sep 22;56(11):1649-59
references: 15350294
references: Int J Pharm. 2006 Jan 3;307(1):89-92
references: 16310989
references: Int J Pharm. 2000 Aug 10;203(1-2):245-53
references: 10967446
references: Biophys Chem. 2004 Jul 1;110(1-2):101-17
references: 15223148
references: Eur J Pharm Biopharm. 2004 Jan;57(1):53-63
references: 14729080
references: Int J Pharm. 2000 Sep 25;206(1-2):35-42
references: 11058808
references: J Colloid Interface Sci. 2005 May 1;285(1):326-35
references: 15797430
references: J Colloid Interface Sci. 2006 Aug 1;300(1):314-26
references: 16603177
references: J Control Release. 2004 Sep 30;99(2):259-69
references: 15380635
references: Crit Rev Oncol Hematol. 2003 Dec;48(3):323-7
references: 14693346
references: Biochim Biophys Acta. 1986 Jan 29;854(2):231-9
references: 3942728
references: Adv Drug Deliv Rev. 2004 Apr 23;56(7):947-65
references: 15066754
references: Acta Paediatr Jpn. 1994 Dec;36(6):613-8
references: 7871968
references: Biomed Pharmacother. 2005 Oct;59(9):491-7
references: 16202557