May 22, 2024
Targeted Drug Delivery

Advancements in Targeted Drug Delivery Nanoparticle-Based Approaches, Cell-Mediated Delivery, and Prodrug Strategies

Nanoparticle-Based Delivery

Nanoparticles have emerged as a leading platform for targeted drug delivery. They can encapsulate or conjugate drugs and guide them towards specific destinations inside the body. Their nanoscale sizes allow them to extravasate from leaky vasculature in diseased tissues like tumors. Various materials like lipids, polymers and inorganic compounds have been engineered to fabricate drug-loaded nanoparticles. Ligands are attached on their surfaces to bind selectively to biomarkers overexpressed on diseased cells.

Liposomes, which are spherical lipid vesicles, were among the earliest nanoparticles explored for delivery. Drugs can be entrapped within their aqueous interiors or embedded in their lipid bilayers. Stealth liposomes containing PEG polymers on their surfaces show evade uptake by the reticuloendothelial system. This enhances their circulation times, allowing increased accumulation at targeted sites. Doxil, the first FDA approved nanomedicine containing liposomal doxorubicin, demonstrated superior treatment of ovarian cancer and Kaposi’s sarcoma.

Polymeric nanoparticles fabricated from materials like PLA, PLGA and chitosan have also generated much interest. Their tunable sizes, shapes and mechanical properties make them versatile carriers. Biodegradable linkages within the polymers enable programmed release of encapsulated drugs. Functionalization with antibodies, peptides or small molecules facilitates active targeting. Abraxane, an albumin-bound nanoparticle formulation of paclitaxel has demonstrated high efficacy against metastatic breast cancers with limited toxicity.

Inorganic nanoparticles such as gold have seen applications in diagnostics, theranostics and photothermal ablation therapies. Their surfaces offer high loading of targeting ligands. Development of silica and magnetic nanoparticles continues for multimodal imaging and delivery applications.

Cell-Mediated Delivery

An Targeted Drug Delivery innovative approach utilizes circulating cells as Trojan horses to selectively deliver therapeutic payloads. Mesenchymal stem cells have an innate ability to home towards sites of injury, inflammation and tumors following systemic administration. They can be pre-loaded with drugs, genes, other cargos or engineered to secrete therapeutic factors. Upon reaching diseased targets, these factors are released from the cells.

Several preclinical and clinical studies have demonstrated effectiveness of stem cell-based delivery of antitumor agents, imaging probes and cytokines against cancers. Genetically modified T cells have also shown promise for delivery of tumor-targeting monoclonal antibodies. Platelets loaded with drugs demonstrate specificity for injured vasculature as they accumulate at sites of arterial thrombi. The biocompatibility and targeting capabilities of cells provide them advantages over other delivery platforms. Optimization of loading techniques and tracking the fate of delivered cells remains an active area of research.

Prodrug Strategies

Prodrugs are pharmacologically inactive derivatives of drug molecules that undergo in vivo transformation to release the active drug. This approach masks reactive functionalities and improves physicochemical properties of drugs to enhance safety and targeting. Several anticancer prodrugs have been designed to selectively release cytotoxic payloads at tumor tissues by exploiting dysregulated enzymes at these sites.

A classical example is 5-fluorouracil, an antimetabolite prodrug converted to the active 5-FU by elevated thymidine phosphorylase levels in tumors. Glufosfamide prodrug exploits tumor-specific glutathione levels to release the alkylating agent phosphoramide mustard. Other strategies have utilized tumor-associated matrix metalloproteinases and low pH microenvironments within tumors to activate prodrugs at these sites. Advancements in understanding tumor biology will facilitate more targeted design of activation-triggered prodrugs with improved therapeutic indices.

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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it