title: Development of zolmitriptan loaded PLGA/poloxamer nanoparticles for migraine using quality by design approach.
abstract: The purpose of this investigation was to develop Poly (D,L Lactide-co-Glycolide) (PLGA)/poloxamer nanoparticles (NPs) of the hydrophilic drug Zolmitriptan using quality-by-design approach for brain targeting. Randomized 2(4) full factorial design was employed to achieve the critical quality attributes of minimized particle size and maximized encapsulation efficiency. The PLGA/poloxamer NPs were fabricated using modified double emulsion solvent diffusion technique and particle size varied from 165.4-245.4 nm, encapsulation efficiency was in the range of 48.96-95.97% and percent cumulative drug release varied from 43.32 to 100%. The optimized nanoparticles were characterized by FTIR spectroscopy and powder X-ray diffraction technique which indicated the loading of drug in NPs without any chemical interactions between drug and the excipients. The uniform and spherical shape of the particles was affirmed from TEM analysis. The in-vivo studies for determination of brain uptake potential demonstrated a 14.13 fold increase in drug delivered to brain from the NPs as compared to the free drug. The pharmacodynamic studies involving Swiss albino mice further confirmed successful delivery of drug to brain circumventing the blood brain barrier, through significantly enhanced anti-migraine potential. This investigation thus presents the suitability of zolmitriptan loaded PLGA/poloxamer NPs in brain targeting for the efficient treatment of migraine.
authors.affiliation: Department of Pharmaceutical Sciences, G.J. University of Sci. & Tech., Hisar 125001, India.
authors.forename: Priti
authors.initials: P
authors.lastname: Girotra
authors.affiliation: Department of Pharmaceutical Sciences, G.J. University of Sci. & Tech., Hisar 125001, India. Electronic address: sksingh_gju@rediffmail.com.
authors.forename: Shailendra Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, G.J. University of Sci. & Tech., Hisar 125001, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D015195:Drug Design; D065546:Drug Liberation; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008881:Migraine Disorders / Q000188:drug therapy / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014363:Tryptamines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D023303:Oxazolidinones; D058825:Serotonin 5-HT1 Receptor Agonists; D014363:Tryptamines; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C089750:zolmitriptan; D019344:Lactic Acid
keywords: Brain targeting; Full factorial design; Migraine