title: pH-Responsive polymeric micelles based on amphiphilic chitosan derivatives: Effect of hydrophobic cores on oral meloxicam delivery.
abstract: The amphiphilic chitosan derivatives, N-naphthyl-N,O-succinyl chitosan (NSCS), N-octyl-N-O-succinyl chitosan (OSCS) and N-benzyl-N,O-succinyl chitosan (BSCS), were synthesized. Meloxicam (MX) was loaded into polymeric micelles (PMs), and the effects of hydrophobic moieties of the inner core segment on the loading efficiency, stability of MX-loaded PMs, cytotoxicity, drug release, and porcine small intestine permeation were investigated. Among the hydrophobic cores, the N-octyl moiety revealed the highest MX loading efficiency and most stable MX-loaded PMs compared to the other hydrophobic cores. All PMs were spherically shaped (size 213-282 nm) and had low toxicity against Caco-2 cells. The release of MX from PMs was found to be dependent on both hydrophobic cores and hydrophilic shells. In acidic medium at 0-2h, low cumulative MX release was obtained in the MX-loaded OSCS PMs compared to MX-loaded NSCS PMs and MX-loaded BSCS PMs as well as MX free drug. However, when the pH was increased to 6.8, the MX release significantly increased in all MX-loaded PMs. Furthermore, the intestinal permeation rates of MX from all MX-loaded PMs were not significantly different. These results suggest that MX was successfully incorporated into the PMs at high efficiency and good stability by optimizing the hydrophobic moieties of the inner core segments.
authors.affiliation: Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
authors.forename: Thisirak
authors.initials: T
authors.lastname: Woraphatphadung
authors.affiliation: National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani 12120, Thailand. Electronic address: warayuth@nanotec.or.th.
authors.forename: Warayuth
authors.initials: W
authors.lastname: Sajomsang
authors.affiliation: National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani 12120, Thailand.
authors.forename: Pattarapond
authors.initials: P
authors.lastname: Gonil
authors.affiliation: National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani 12120, Thailand.
authors.forename: Alongkot
authors.initials: A
authors.lastname: Treetong
authors.affiliation: Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
authors.forename: Prasert
authors.initials: P
authors.lastname: Akkaramongkolporn
authors.affiliation: Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
authors.forename: Tanasait
authors.initials: T
authors.lastname: Ngawhirunpat
authors.affiliation: Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand. Electronic address: opanasopit_p@su.ac.th.
authors.forename: Praneet
authors.initials: P
authors.lastname: Opanasopit
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007421:Intestine, Small / Q000378:metabolism; D000077239:Meloxicam; D008823:Micelles; D010316:Particle Size; D010539:Permeability; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013552:Swine; D013843:Thiazines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D013844:Thiazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D013843:Thiazines; D013844:Thiazoles; D048271:Chitosan; D000077239:Meloxicam
keywords: Chitosan; Hydrophobic cores; Meloxicam; pH Responsive polymeric micelles