Thermosensitive hydrogels for nasal drug delivery: the formulation and characterisation of systems based on N-trimethyl chitosan chloride.
Towards the development of a thermosensitive drug-delivery vehicle for nasal delivery, a systematic series of N-trimethyl chitosan chloride polymers, synthesised from chitosans of three different average molecular weights, have been co-formulated into a hydrogel with poly(ethylene glycol) and glycerophosphate. Rheological evaluations have shown that hydrogels derived from N-trimethyl chitosan with a low degree of quaternisation and high or medium average molecular weight exhibit relatively short sol-gel transition times at physiologically relevant temperatures. Also, the same hydrogels display good water-holding capacity and strong mucoadhesive potential, and their mixtures with mucus exhibit rheological synergy. An aqueous hydrogel formulation, derived from N-trimethyl chitosan of medium average molecular weight and low degree of quaternisation, appears particularly promising in that it exhibits most favourable rheological and mucoadhesive behaviour and a sol-gel transition that occurs at 32.5°C within 7 min.
School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
H
H
Nazar
D G
DG
Fatouros
S M
SM
van der Merwe
N
N
Bouropoulos
G
G
Avgouropoulos
J
J
Tsibouklis
M
M
Roldo
D000281:Administration, Intranasal; D055598:Chemical Phenomena; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D009079:Mucociliary Clearance; D044367:Phase Transition; D012212:Rheology; D013696:Temperature; D044366:Transition Temperature; D014783:Viscosity; D014867:Water / Q000737:chemistry
D004337:Drug Carriers; D020100:Hydrogels; C118071:N-trimethyl chitosan chloride; D014867:Water; D048271:Chitosan