title: Formulation, functional evaluation and ex vivo performance of thermoresponsive soluble gels - A platform for therapeutic delivery to mucosal sinus tissue.
abstract: Mucoadhesive in situ gelling systems (soluble gels) have received considerable attention recently as effective stimuli-transforming vectors for a range of drug delivery applications. Considering this fact, the present work involves systematic formulation development, optimization, functional evaluation and ex vivo performance of thermosensitive soluble gels containing dexamethasone 21-phosphate disodium salt (DXN) as the model therapeutic. A series of in situ gel-forming systems comprising the thermoreversible polymer poloxamer-407 (P407), along with hydroxypropyl methyl cellulose (HPMC) and chitosan were first formulated. The optimized soluble gels were evaluated for their potential to promote greater retention at the mucosal surface, for improved therapeutic efficacy, compared to existing solution/suspension-based steroid formulations used clinically. Optimized soluble gels demonstrated a desirable gelation temperature with Newtonian fluid behaviour observed under storage conditions (4-8°C), and pseudoplastic fluid behaviour recorded at nasal cavity/sinus temperature (≈34°C). The in vitro characterization of formulations including rheological evaluation, textural analysis and mucoadhesion studies of the gel form were investigated. Considerable improvement in mechanical properties and mucoadhesion was observed with incorporation of HPMC and chitosan into the gelling systems. The lead poloxamer-based soluble gels, PGHC4 and PGHC7, which were carried through to ex vivo permeation studies displayed extended drug release profiles in conditions mimicking the human nasal cavity, which indicates their suitability for treating a range of conditions affecting the nasal cavity/sinuses.
authors: School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, Australia.
authors: Preeti
authors: P
authors: Pandey
authors: School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, Australia.
authors: Peter J
authors: PJ
authors: Cabot
authors: School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, Australia; Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, Australia.
authors: Benjamin
authors: B
authors: Wallwork
authors: Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, Australia; School of Medicine, The University of Queensland, Brisbane, Australia.
authors: Benedict J
authors: BJ
authors: Panizza
authors: School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, Australia. Electronic address: h.parekh@uq.edu.au.
authors: Harendra S
authors: HS
authors: Parekh
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005782:Gels; D006801:Humans; D065347:Hypromellose Derivatives / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010256:Paranasal Sinuses / Q000187:drug effects / Q000378:metabolism; D020442:Poloxamer / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013552:Swine; D013696:Temperature
chemical_list: D005782:Gels; D020442:Poloxamer; D065347:Hypromellose Derivatives; D048271:Chitosan
keywords: Dexamethasone; Human nasal mucosa; Intranasal soluble gels; Poloxamer 407; Sinusitis