In Vivo Properties of an In Situ Forming Gel for Parenteral Delivery of Macromolecular Drugs

Purpose. This study characterizes the in vivoproperties of an in situforming gel, comprising an IPC of water-soluble polymers, PMA and PEG, for sustained release of macromolecular drugs.Methods. 40, 50 or 60% w/v formulations were injected subcutaneously in a rat model either alone, or containing model macromolecules, 3A2-ATG-psODN or REV-psODN, to (i) determine the approximate gelling and residence time of the gel at the site of injection, (ii) assess the biological efficacy of the formulation using a MZ sleep time model, and (iii) demonstrate specificity of the sequence and selectivity of the psODNs by measuring changes in microsomal enzyme levels and urine volumes.Results. A sol to gel transition requires 15 min in vivo, and the 60% w/v IPC gel remains at the site of injection for up to 72 hr. The MZ sleep times and CYP3A2 expression due to 3A2-ATG-psODNs released from the gel are significantly different compared to that of REV-psODNs.Conclusions. The IPC solutions exhibit phase transformation in vivo, and demonstrate no evidence of toxicity. The pharmacological effects observed from the of release of 3A2-ATG-psODNs suggest that the formulation can entrap, protect, and sustain the delivery of macromolecules.