title: Lecithin and PLGA-based self-assembled nanocomposite, Lecithmer: preparation, characterization, and pharmacokinetic/pharmacodynamic evaluation.
abstract: The present study investigates the drug delivery potential of polymer lipid hybrid nanocomposites (Lecithmer®) composed of poly(D,L-lactide-co-glycolide (PLGA) and soya lecithin. Core-shell structure of Lecithmer was evident from cryo-TEM images. Daunorubicin (DNR) and lornoxicam (LNX)-incorporated Lecithmer nanocomposites were evaluated for anticancer and anti-inflammatory activity. DNR- and LNX-loaded Lecithmer had mean particle size of ∼335 and ∼282.7 nm, respectively. Lecithmer formulated with different cationic lipids resulted in lower particle size (∼120 nm) and positive zeta potential. Entrapment efficiency of DNR and LNX was 93.16 and 88.59 %, respectively. In vitro release of DNR from Lecithmer was slower compared to PLGA nanoparticles. DNR release from Lecithmer was significantly higher at pH 5.5 (80.96 %) as compared to pH 7.4 (55.95 %), providing advantage for selective tumor therapy. Similarly, sustained release of LNX (30 % in 10 h) was observed at pH 7.4. DNR in Lecithmer showed superior cytotoxicity on human erythroleukemic K562 cells. Pharmacokinetic study in Wistar rats with i.v. administered DNR-loaded Lecithmer showed higher volume of distribution, lower elimination rate constant, and longer half-life (81.68 L, 0.3535 h(-1), 1.96 h) as compared to DNR solution (57.46 L, 0.4237 h(-1), 1.635 h). Pharmacodynamic evaluation of orally administered LNX-loaded Lecithmer showed superior anti-inflammatory activity with maximum inhibition of 81.2 % vis-à-vis 53.57 % in case of LNX suspension. In light of these results, Lecithmer can be envisaged as a promising nanosystem for parenteral as well as oral drug delivery.
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400 098, India.
authors.forename: Seby Elsy
authors.initials: SE
authors.lastname: Varghese
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400 098, India.
authors.forename: Mayur K
authors.initials: MK
authors.lastname: Fariya
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400 098, India.
authors.forename: Gopal Singh
authors.initials: GS
authors.lastname: Rajawat
authors.affiliation: Center for Electron Microscopy of the Medical Faculty, Friedrich-Schiller-University Jena, Ziegelmühlenweg 1, 07740, Jena, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Steiniger
authors.affiliation: Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Lessingstr. 8, 07743, Jena, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Fahr
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400 098, India. mangal.nagarsenker@gmail.com.
authors.forename: Mangal S
authors.initials: MS
authors.lastname: Nagarsenker
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003630:Daunorubicin / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004487:Edema / Q000517:prevention & control; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D054709:Lecithins / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000494:pharmacology; D011091:Polyesters / Q000493:pharmacokinetics*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats
chemical_list: D003692:Delayed-Action Preparations; D054709:Lecithins; C000625733:Lecithmer; D011091:Polyesters; D010894:Piroxicam; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C059451:lornoxicam; D003630:Daunorubicin
keywords: Anti-inflammatory; Anticancer; Daunorubicin; Hybrid nanocomposite; Lornoxicam