title: Physical characterisation and long-term stability studies on quaternary ammonium palmitoyl glycol chitosan (GCPQ)--a new drug delivery polymer.
abstract: N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) is a self-assembling polymer, which enables the oral bioavailability of peptide and hydrophobic drugs. In preparation for clinical testing, here we examine GCPQ's synthesis reproducibility, pKa, thermal, and rheological properties. GCPQ was synthesised by acid degradation of glycol chitosan (GC), reaction with palmitic acid N-hydroxysuccinimide (PNS) and methylation. A GC monomer, PNS molar feed ratio of 0.92 together with a gravimetric feed ratio for N-palmitoyl-6-O-glycolchitosan, methyl iodide of 3.3, reproducibly produces GCPQ48 (Mw = 19.9 ± 9.9 kDa, Mn = 13.1 ± 2.4 kDa, mol % palmitoylation = 23 ± 2.7, mol % quaternisation = 10 ± 0.23, n = 56). GCPQ48 decomposes at 218 ± 4.3 °C, is glassy at room temperature (Tg = 164.4 ± 8.5 °C), is a weak base (pKa = 5.99 ± 0.15), and produces micellar dispersions at neutral pH. Below a concentration of 0.07 g mL(-1) , GCPQ48 dispersions showed Newtonian rheological behaviour but at higher concentrations, the polymer undergoes shear thinning because of the chain disentanglement at high shear rates. GCPQ48 forms a network of micelles and concentrated (0.09 g mL(-1) ) dispersions are viscoelastic, with the storage modulus exceeding the loss modulus at high frequencies. Solid GCPQ48 was stable when stored at room temperature for 18 months.
authors.affiliation: UCL School of Pharmacy, University College London, London, UK.
authors.forename: Kar Wai
authors.initials: KW
authors.lastname: Chooi
authors.forename: Margarida Isabel
authors.initials: MI
authors.lastname: Simão Carlos
authors.forename: Ramesh
authors.initials: R
authors.lastname: Soundararajan
authors.forename: Simon
authors.initials: S
authors.lastname: Gaisford
authors.forename: Natrah
authors.initials: N
authors.lastname: Arifin
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Schätzlein
authors.forename: Ijeoma F
authors.initials: IF
authors.lastname: Uchegbu
mesh_terms: D064751:Ammonium Compounds / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D012212:Rheology; D014783:Viscosity
chemical_list: D064751:Ammonium Compounds; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; C114305:palmitoyl glycol chitosan; D048271:Chitosan
keywords: drug delivery systems; micellar networks; nanoparticles; pKa; polymer synthesis; polymeric micelles; quaternary ammonium palmitoyl glycol chitosan (GCPQ); thermal analysis; viscosity