ArticlePharmaceutical research2026
Liposomal Formulation of a Tetravalent Oxaliplatin Prodrug: Preparation and Antitumor Efficacy.
Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveTo overcome the limitations of oxaliplatin (OXA) in triple-negative breast cancer (TNBC) therapy-including glutathione (GSH)-induced resistance, poor lipophilicity, low cellular uptake, and significant off-target toxicity.
methodsBased on the "like dissolves like" concept, two amphiphilic tetravalent oxaliplatin (OXA(IV)) prodrugs modified with double long alkyl chains were synthesized. Through formulation screening and optimization, liposomes loaded with OXA(IV) prodrugs containing octane (OXA(IV)-C8LIP) and dodecane (OXA(IV)-C12LIP) alkyl chains were effectively prepared using microfluidic technology, achieving good encapsulation efficiency and drug loading.
resultsCompared with free OXA, the liposomal formulations exhibited higher cellular uptake, improved cytotoxicity against TNBC cells, and dramatically enhanced tumor accumulation via the enhanced permeability and retention (EPR) effect. In vivo, they substantially extended plasma half-life, demonstrated excellent antitumor efficacy, and showed low systemic toxicity. According to the well-established mechanism of Pt(IV) prodrugs, the reductive activation of these compounds is expected to deplete intracellular glutathione (GSH) and elevate reactive oxygen species (ROS), potentially contributing to the reversal of drug resistance and enhanced cytotoxicity.
conclusionThese OXA(IV) liposomes represent a promising nanomedicine for TNBC therapy. Moreover, the simple prodrug encapsulation strategy may be extended to other antitumor drugs with poor stability and short half-life.
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