Poly(lactic acid) microspheres for the sustained release of a selective A(1) receptor agonist

A study concerning the feasibility of microsphere use as sustained delivery systems for N-6-cyclopentyladenosine (CPA) administration has been perform ed. The release of this drug and the related stability effects in human who le blood have been rested. Moreover. the impact of the delivery system on C PA interaction toward human adenosine A, receptor and the related cellular responses has been analyzed. The microspheres were prepared by an emulsion- solvent evaporation method using poly(lactic acid). Free and encapsulated C PA was incubated in fresh blood and the drug stability was analyzed with HP LC. The affinity of CPA to human A, receptor expressed by CHO cells was obt ained by binding experiments. Activity was evaluated by measurements of the inhibition of forskolin-stimulated 3',5'-cyclic adenosine monophosphate (c -AMP) performing competitive binding assays. Encapsulated CPA was released within 72 h and its degradation in blood was negligible. Affinity and activ ity values of CPA obtained in the absence and in the Presence of unloaded m icrospheres were the same. CPA encapsulation in microspheres allows its sus tained release and its stabilization in human whole blood to be obtained. T he presence of this release system does not interfere with the CPA activity at its action site. (C) 2001 Elsevier Science B.V. All rights reserved.