Paradigm-shifting modalities to more efficiently deliver drugs to cancerous lesions require the following attributes: nanoscale-size, targetability and stability under physiological conditions. Often, these nanoscale drug delivery vehicles are limited due to agglomeration, poor solubility or cytotoxicity. Thus, we have designed a methodology to encapsulate hydrophobic antineoplastic chemotherapeutics within a 20-30 nm diameter, pH-responsive, non-agglomerating, non-toxic calcium phosphate nanoparticle matrix. In the present study, we report on calcium phosphate nanocomposite particles (CPNP) that encapsulate both fluorophores and chemotherapeutics, are colloidally stable in physiological solution for extended time at 37°C and can efficaciously deliver hydrophobic antineoplastic agents, such as ceramide, in several cell model systems.
ABSTRACT:Ceramide, an endogenous sphingolipid, has demonstrated antineoplastic activity in vitro and in vivo. However, the chemotherapeutic utility of ceramide is limited because of its insolubility. To increase the solubility of ceramide, liposomal delivery systems have been used. The objective of the present study was to characterize the pharmacokinetics and tissue distribution of C6-ceramide and control (non-C6-ceramide) nanoliposomes in rats, using
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