Sonopermeation using microbubbles is an emerging extracorporeal drug delivery technique for impenetrable tumors. Utilizing the sonopermeation effect while enhancing the bioavailability of clinical chemotherapeutics using nanoparticle strategies is a potentially powerful combination. Clinically available topotecan, a chemotherapeutic, has limited bioavailability and therapeutic efficacy, which is attributed to poor solubility, rapid clearance, and inactivation under physiologic conditions. To overcome this, topotecan has been conjugated with phospholipids converting it into a lipid-prodrug (2T-T) for use in lipid-based carriers, such as liposomes, for sonopermeation. In this presentation, we present the characterization results of topotecan lipid-prodrug liposomes, preliminary in vitro efficacy in several neuroblastoma cell lines, and in vivo proof-of-concept in neuroblastoma xenograft tumors. Lipid-prodrug characterization demonstrates stable, high-drug loading liposomes are attainable while maintaining cytotoxicity. Liposome formulations, analyzed using ultraviolet-visible spectrometry and dynamic light scattering, indicate peak incorporation limits are attained for 100 nm extruded 60 mol. % 2T-T liposomes with no change in size over a 2 month period. In vivo xenograft neuroblastoma studies co-injected with lipid-prodrug liposomes (40 mol% 2T-T, 10 mg/kg) and microbubbles, for sonopermeation, were performed to determine the extent of 2T-T delivery with sonoporation over liposomal delivery alone at 24 hours post-treatment.
The world is facing major issues related to antibiotic resistance, specific drugs targeting and its side effects. Such obstacles can be rectified by nanotechnology as they have essential characteristics with smaller size, target specificity, easy deliverable with lesser side effects. The prime nature of the nanoparticles are, it can probe into the cell wall of the pathogenic microbes and even have the capacity to intrude into cellular pathways. Nanoparticles themselves are capable of destroying unwanted foreign particles or toxic cells, which enter into our bodies. Nanoparticles can be treated as carriers, in which they combine with specific drugs and deliver to target specific cells with lesser side effects. Nanoparticles are used as a drug delivery agent for various kinds of diseases related to cancer. Nanoparticles with drugs increase the antibiotic release at the different target sites and these nanoparticles have a great tendency to deliver a large number of drugs to a cell. In this current review, we discuss the bright future of NPs as drug delivery agents as it can overcome all conventional problems.
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