Co-delivery Of Multiple Agents Research Articles

Lipid-based Nanoparticulate Drug Delivery.

The emergence of lipid-based nanoparticulate systems has significantly reshaped the landscape of drug delivery. This review encapsulates the advancements, challenges, and potential of lipid-based nanoparticulate drug delivery in modern therapeutics. Lipid-based nanoparticles, including liposomes, lipid nanoparticles, and solid lipid nanoparticles, harness the biocompatibility and biodegradability of lipids to encapsulate and deliver a diverse range of therapeutic agents. This platform offers solutions to various drug delivery challenges, such as enhancing drug solubility and bioavailability, achieving controlled and sustained release, targeted delivery, and co-delivery of multiple agents. These nanoparticles have demonstrated potential in overcoming biological barriers, including the blood-brain barrier, mucosal barriers, and cellular barriers, enabling the delivery of drugs to previously inaccessible sites. Biocompatibility and reduced toxicity are intrinsic attributes of lipid-based nanoparticles, minimizing immune responses and systemic toxicity while promoting personalized medicine possibilities. However, challenges in formulation, stability, and regulatory approval underscore the need for ongoing research and innovation in this field.

Nanotechnology - a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer.

Genomic and proteomic mutation analysis is the standard of care for selecting candidates for therapies with tyrosine kinase inhibitors against the human epidermal growth factor receptor (EGFR TKI therapies) and further monitoring cancer treatment efficacy and cancer development. Acquired resistance due to various genetic aberrations is an unavoidable problem during EGFR TKI therapy, leading to the rapid exhaustion of standard molecularly targeted therapeutic options against mutant variants. Attacking multiple molecular targets within one or several signaling pathways by co-delivery of multiple agents is a viable strategy for overcoming and preventing resistance to EGFR TKIs. However, because of the difference in pharmacokinetics among agents, combined therapies may not effectively reach their targets. The obstacles regarding the simultaneous co-delivery of therapeutic agents at the site of action can be overcome using nanomedicine as a platform and nanotools as delivery agents. Precision oncology research to identify targetable biomarkers and optimize tumor homing agents, hand in hand with designing multifunctional and multistage nanocarriers that respond to the inherent heterogeneity of the tumors, may resolve the challenges of inadequate tumor localization, improve intracellular internalization, and bring advantages over conventional nanocarriers.

Individually coated microneedles for co-delivery of multiple compounds with different properties.

Microneedle (MN) patches provide a simple method for delivery of drugs that might otherwise require hypodermic injection. Conventional MN patch fabrication methods typically can load only one or possibly multiple miscible agents with the same formulation on all MNs, which limits the combination and spatial distribution of drugs and formulations having different properties (such as solubility) in a single patch. In this study, we coated MNs individually instead of coating all MNs from the same formulation, making possible a patch where each individual MN is coated with different formulations and drugs. In this way, individually coated MN patches co-delivered multiple agents with different physicochemical characteristics (immiscible molecules, proteins, and nanoparticles) and in different spatial patterns in the skin. MN loading was adjusted by modifying the number of coating layers, and co-delivery of multiple agents was demonstrated in the porcine skin. We conclude that individually coating MNs enables co-delivery of multiple different compounds and formulations with needle-by-needle spatial control in the skin.

Subcellular co-delivery of two different site-oriented payloads for tumor therapy.

Co-delivery of multiple agents via nanocarriers is of great interest in cancer therapy, but subcellular delivery to the corresponding site of action remains challenging. Here we report a smart nanovehicle which enables two different site-oriented payloads to reach their targeted organelles based on stimulus-responsive release and nucleus-targeted modification. First, all trans retinoic acid (RA) conjugated camptothecin (RA-CPT) was loaded in a polyhedral oligomericsilsesquioxane (POSS)-based core; docetaxel (DTX) was grafted on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. The POSS core grafted with semitelechelic HPMA copolymers then self-assembled into micelles. Once internalized into the cell, the two drugs were unleashed environment-responsively, and nuclear targeted RA remarkably facilitated the nuclear transport of CPT. Compared with single drug-loaded micelles, the dual drug-loaded platform showed superior synergic cytotoxicity, which was further strengthened by the involvement of RA. The ability to induce DNA damage and apoptosis was also enhanced by nucleus-targeted modification. Finally, dual drug-loaded micelles exhibited much better in vivo tumor inhibition (87.1%) and less systemic toxicity than the combination of single drug-loaded systems or the dual drug-loaded micelles without RA. Therefore, our study provides a novel "one platform, two targets" strategy in combinatory anti-cancer therapy.