Disturbances in social interaction occur along with pathophysiological deficits following sub-chronic phencyclidine administration in the rat.

A sub-chronic administration of phencyclidine to the rat brings about enduring pathophysiological and cognitive changes that resemble some features of schizophrenia. The present study aimed to determine whether the behavioural consequence of this phencyclidine regime extends to a long-term disruption of social interaction that might provide a parallel with some negative symptoms of the disease. Rats were treated with phencyclidine (2mg/kg bi-daily for 1 week) or vehicle followed by a drug-free period. Social interaction was assessed 24h, 1 week, 3 weeks and 6 weeks post-treatment. A long-lasting disturbance of social behaviour was observed in the phencyclidine group, namely more contact and non-contact interaction with an unfamiliar target rat at all time points. Six weeks post-phencyclidine, analysis of brains showed a reduction in expression of parvalbumin immunoreactive neurons in the hippocampus with significant reductions localised to the CA1 and dentate gyrus regions. These results show that sub-chronic phencyclidine produces long-lasting disruptions in social interaction that, however, do not model the social withdrawal seen in patients with schizophrenia. These disturbances of social behaviour may be associated with concurrent pathophysiological brain changes.

Characterization of the Rheological, Mucoadhesive, and Drug Release Properties of Highly Structured Gel Platforms for Intravaginal Drug Delivery

This investigation describes the formulation and characterization of theologically structured vehicles (RSVs) designed for improved drug delivery to the vagina. Interactive, multicomponent, polymeric platforms were manufactured containing hydroxyethylcellulose (HEC, 5% w/w) polyvinylpyrrolidone (PVP, 4% w/w), Pluronic (PL, 0 or 10% w/w), and either polycarbophil (PC, 3% w/w) or poly(methylvinylether-co-maleic anhydride) (Gantrez S97, 3% w/w) as a mucoadhesive agent. The rheological (torsional and dynamic), mechanical (compressional), and mucoadhesive properties were characterized and shown to be dependent upon the mucoadhesive agent used and the inclusion/exclusion of PL. The dynamic theological properties of the gel platforms were also assessed following dilution with simulated vaginal fluid (to mimic in vivo dilution). RSVs containing PC were more rheologically structured than comparator formulations containing GAN. This trend was also reflected in formulation hardness, compressibility, consistency, and syringeability. Moreover, formulations containing PL (10% w/w) were more theologically structured than formulations devoid of PL. Dilution with simulated vaginal fluids significantly decreased rheological structure, although RSVs still retained a highly elastic stnicture (G' > G '' and tan delta <1). Furthermore, RSVs exhibited sustained drug release properties that were shown to be dependent upon their rheological structure. It is considered that these semisolid drug delivery systems may be useful as site-retentive platforms for the sustained delivery of therapeutic agents to the vagina.

An examination of the rheological and mucoadhesive properties of poly(Acrylic acid) organogels designed as platforms for local drug delivery to the oral cavity

This study examined the rheological/mucoadhesive properties of poly (acrylic acid) PAA organogels as platforms for drug delivery to the oral cavity. Organogels were prepared using PAA (3%, 5%, 10% w/w) dissolved in ethylene glycol (EG), propylene glycol (PG), 1,3-propylene glycol (1,3-PG), 1,5-propanediol (1,5-PD), polyethylene glycol 400 (PEG 400), or glycerol. All organogels exhibited pseudoplastic flow. The increase in storage (G') and loss (G '') moduli of organogels as a function of frequency was minimal, G '' was greater than G '' (at all frequencies), and the loss tangent <1, indicative of gel behavior. Organogels prepared using EG, PG, and 1,3-propanediol (1,3-PD) exhibited similar flow/viscoelastic properties. Enhanced rheological structuring was associated with organogels prepared using glycerol (in particular) and PEG 400 due to their interaction with adjacent carboxylic acid groups on each chain and on adjacent chains. All organogels (with the exception of 1,5-PD) exhibited greater network structure than aqueous PAA gels. Organogel mucoadhesion increased with polymer concentration. Greatest mucoadhesion was associated with glycerol-based formulations, whereas aqueous PAA gels exhibited the lowest mucoadhesion. The enhanced network structure and the excellent mucoadhesive properties of these organogels, both of which may be engineered through choice of polymer concentration/solvent type, may be clinically useful for the delivery of drugs to the oral cavity.