The retention of 14C-labelled poly(acrylic acids) on gastric and oesophageal mucosa: an in vitro study
Smart, J.D., Riley, R.G., Tsibouklis, J., Young, S.A., Hampson, F.C., Davis, J.A., Kelly, G., Dettmar, P.W. and Wilber, W.R. (2003) The retention of 14C-labelled poly(acrylic acids) on gastric and oesophageal mucosa: an in vitro study European journal of pharmaceutical sciences, 20 (1). pp. 83-90. ISSN 0928-0987
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Official URL: http://dx.doi.org/10.1016/S0928-0987(03)00175-1
Polymers that bind from solution onto gastric mucosa can be used either as a means of facilitating localised drug delivery, or can act as therapeutic agents in their own right (e.g. by forming a protective layer or by inhibiting enzymes). In our previous study [Int. J. Pharm. 236 (2002) 87], the binding and retention of labelled poly(acrylic acid)s on sections of gastric mucosa from pigs was evaluated using ‘dynamic flow’ conditions and a high molecular weight poly(acrylic acid) was found to bind most avidly. In the current study, 3% solutions of ‘low’, ‘high’ and ‘ultra high’ molecular weight polymers were evaluated in the ‘dynamic flow’ model for their ability to bind to tissues from the fundic and pyloric regions of the stomach and the oesophagus of pigs. All the polymers tested were retained on each mucosa for extended periods; the high and ultra high molecular weight polymers showed the greatest retention. Examination of the kinetics of polymer elution suggested that two fractions exist, ‘bound’ and ‘unbound’ polymer, showing differing retention profiles. The high molecular weight polymer showed the greatest retention on pyloric tissue, particularly on the upper sections. The retention of the ultra high and high molecular weight polymer was similar on the fundic and oesophageal mucosa, and the distribution was even across the tissue. It was concluded that poly(acrylic acid) binding from solution presents a therapeutic opportunity, and the differences in binding and retention of the polymers on the different mucosae could present an opportunity for targeting.
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