Evaluation of carboplatin sustained‐release delivery system in dogs with cancer

Abstract

The objective of the study was to assess the carboplatin sustained‐release (CSR) as an injectable, biodegradable polymer system designed to uniformly release carboplatin over 30 days at a dose of 350 mg m−2. The study involved seven client‐owned dogs with histologically or cytologically confirmed neoplasia that were treated with CSR intramuscularly. Platinum levels were measured at days 0, 7, 14, 21 and 28. Complete blood cell (CBC) counts, body weight, local toxicity and side effects were also evaluated at the time of platinum measurement at days 0, 7, 14, 21 and 28. CSR released carboplatin steadily over 30 days. Neutropenia was noted as Grade 3 in one dog (14%) and Grade 4 in two dogs (29%) at day 14, and Grade 4 in one dog (14%) at day 21. Thrombocytopenia was noted as Grade 2 in four dogs (57%), Grade 3 in one dog (14%) and Grade 4 in one dog (14%) at day 14; Grade 2 in two dogs (29%) and Grade 3 in one dog (14%) at days 21 and 28. Grade 1 lethargy in one dog (14%) and Grade 1 nausea in dog (14%) occurring within 7 days after administration. No obvious local injection site reactions were noted. CSR administered at 350 mg m−2 intramuscularly resulted in a steady release over 30 days. Myelosuppression (Grade 4) was noted in 86% of patients. CSR released the drug slowly and steadily, however additional studies are needed to assess acceptable dosage requirements.

Modified Carboxyl-Terminated PAMAM Dendrimers as Great Cytocompatible Nano-Based Drug Delivery System

“…After crossing the cell membrane and entering cells, CPT molecules are intracellularly activated by undergoing the hydrolysis of 1,1-cyclobutanedicarboxylate, becoming positively charged [3]. This allows CPT to form reactive platinum complexes that create inter-strand and intra-strand crosslinks with DNA and protein, thereby impeding DNA replication, transcription, and translation and suppressing proliferation [4]. In spite of having a similar molecular mechanism of action in cancer cells, CPT exhibits lower reactivity and toxicity compared to the first generation platinum-containing cisplatin, with no nephrotoxicity, ototoxicity, and neurotoxicity [5].…”