title: Hydrophobically modified inulin as an amphiphilic carbohydrate polymer for micellar delivery of paclitaxel for intravenous route.
abstract: Micellization offers several advantages for the delivery of water insoluble drugs including a nanoparticulate 'core-shell' delivery system for drug targeting. Recently, hydrophobically modified polysaccharides (HMPs) are gaining recognition as micelle forming polymers to encapsulate hydrophobic drugs. In this manuscript, for the first time, we have evaluated the self-assembling properties of a lauryl carbamate derivative of the poly-fructose natural polymer inulin (Inutec SP1(®) (INT)) to form paclitaxel (PTX) loaded micelles. INT self-assembled into well-defined micellar structures in aqueous environment with a low critical micellar concentration of 27.8 μg/ml. INT micelles exhibited excellent hemocompatibility and low toxicity to cultured cells. PTX loaded INT micelles exhibited a mean size of 256.37 ± 10.45 nm with excellent drug encapsulation efficiency (95.66 ± 2.25%) and loading (8.69 ± 0.22%). PTX loaded micelles also displayed sustained release of PTX and enhanced anti-cancer efficacy in-vitro in mouse melanoma cells (B16F10) compared to Taxol formulation with Cremophor EL as solvent. In addition, PTX loaded INT micelles exhibited comparable in-vivo antitumor activity in B16F10 allograft mouse model at half the dose of Taxol. In conclusion, INT offers safe, inexpensive and natural alternative to widely used PEG-modified polymers for the formulation of micellar delivery systems for paclitaxel.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, SAV # 255, Box 2202C, Brookings, South Dakota 57007, United States.
authors.forename: Pratik
authors.initials: P
authors.lastname: Muley
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, SAV # 255, Box 2202C, Brookings, South Dakota 57007, United States.
authors.forename: Sunny
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, SAV # 255, Box 2202C, Brookings, South Dakota 57007, United States.
authors.forename: Fadoua
authors.initials: F
authors.lastname: El Kourati
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, SAV # 255, Box 2202C, Brookings, South Dakota 57007, United States.
authors.forename: Siddharth S
authors.initials: SS
authors.lastname: Kesharwani
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, SAV # 255, Box 2202C, Brookings, South Dakota 57007, United States. Electronic address: hemachand.tummala@sdstate.edu.
authors.forename: Hemachand
authors.initials: H
authors.lastname: Tummala
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D065546:Drug Liberation; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007444:Inulin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D008810:Mice, Inbred C57BL; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D007444:Inulin; D017239:Paclitaxel
keywords: Carbohydrate polymer; Inulin; Inutec SP1(®); Melanoma; Micelles; Paclitaxel; Xenograft