Abstract
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.
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Joshi, R., Arora, V., Desjardins, J.P. et al. In Vivo Properties of an In Situ Forming Gel for Parenteral Delivery of Macromolecular Drugs. Pharm Res 15, 1189–1195 (1998). https://doi.org/10.1023/A:1011979505697
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DOI: https://doi.org/10.1023/A:1011979505697