title: Nanostructured lipid carriers based nanogel for meloxicam delivery: mechanistic, in-vivo and stability evaluation.
abstract: OBJECTIVE
  Our investigation was aimed to investigate the potential suitability of meloxicam-loaded nanostructured lipid carriers (MLX-NLC) gel for topical application.
  
  
  METHODS
  MLX-NLC gel was prepared and in vivo skin penetration ability of the NLC gel was evaluated using confocal laser scanning microscopy. We studied the effect of MLX-NLC gel on the changes in lipid profile of skin to get an insight into its skin penetration enhancement mechanism. Acetic acid induced writhing test was performed to evaluate the analgesic effect. Drug concentration-time profile of MLX in rat plasma and skin after topical and oral treatment with MLX-NLC gel and oral MLX-solution, respectively, was observed. MLX-NLC gel was subjected to primary skin irritation test, sub-acute dermal toxicity study. Storage stability of MLX-NLC gel was also assessed for 90 days.
  
  
  RESULTS
  NLC gel was effective in permeating Rhodamine 123 to deeper layers of rat skin. Changes in skin lipid prolife were observed in the rat skin on treatment with MLX-NLC gel and the results supported skin lipid extraction as a possible penetration enhancement mechanism. MLX-NLC gel demonstrated sustained pain inhibitory effect. Pharmacokinetics study established that topical application of MLX-NLC gel had the potential to avoid systemic uptake and hence the risk of systemic adverse effects. MLX-NLC gel demonstrated good skin tolerability and biosafety. Excellent physical stability of nanogel was observed at 4 ± 2 °C.
  
  
  CONCLUSIONS
  The study revealed that NLC gel is a promising carrier system for the topical application of MLX without side effects.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University , Amritsar, Punjab , India and.
authors.forename: S
authors.initials: S
authors.lastname: Khurana
authors.forename: N K
authors.initials: NK
authors.lastname: Jain
authors.forename: P M S
authors.initials: PM
authors.lastname: Bedi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D005260:Female; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D000077239:Meloxicam; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D013843:Thiazines / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D013844:Thiazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D008055:Lipids; D000080385:Nanogels; D013843:Thiazines; D013844:Thiazoles; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D000077239:Meloxicam
keywords: Analgesic; meloxicam; nanostructured lipid carriers; skin tolerance; storage stability