Recent Advancement in Biotechnology and Drug Development Using Cutting-Edge Platforms

One strategy to prevent islet rejection is to create a favorable immune-protective local environment at the transplant site. Herein, we utilize localized cyclosporine A (CsA) delivery to islet grafts via poly(lactic-co-glycolic acid) (PLGA) microparticles to attenuate allograft rejection. CsA-eluting PLGA microparticles were prepared using a single emulsion (oil-in-water) solvent evaporation technique. CsA microparticles alone significantly delayed islet allograft rejection compared to islets alone (p < 0.05). Over 50% (6/11) of recipients receiving CsA microparticles and short-term cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig) therapy displayed prolonged allograft survival for 214 days, compared to 25% (2/8) receiving CTLA4-Ig alone. CsA microparticles alone and CsA microparticles + CTLA4-Ig islet allografts exhibited reduced T-cell (CD4⁺ and CD8⁺ cells, p < 0.001) and macrophage (CD68⁺ cells, p < 0.001) infiltration compared to islets alone. We observed the reduced mRNA expression of proinflammatory cytokines (IL-6, IL-10, INF-γ, and TNF-α; p < 0.05) and chemokines (CCL2, CCL5, CCL22, and CXCL10; p < 0.05) in CsA microparticles + CTLA4-Ig allografts compared to islets alone. Long-term islet allografts contained insulin⁺ and intra-graft FoxP3⁺ T regulatory cells. The rapid rejection of third-party skin grafts (C3H) in islet allograft recipients suggests that CsA microparticles + CTLA4-Ig therapy induced operational tolerance. This study demonstrates that localized CsA drug delivery plus short-course systemic immunosuppression promotes an immune protective transplant niche for allogeneic islets. Full article

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality globally. Despite significant advancements in the development of pharmacological therapies, the challenges of targeted drug delivery to the cardiovascular system persist. Innovative drug-delivery systems have been developed to address these challenges and improve therapeutic outcomes in CVDs. This comprehensive review examines various drug delivery strategies and their efficacy in addressing CVDs. Polymeric nanoparticles, liposomes, microparticles, and dendrimers are among the drug-delivery systems investigated in preclinical and clinical studies. Specific strategies for targeted drug delivery, such as magnetic nanoparticles and porous stent surfaces, are also discussed. This review highlights the potential of innovative drug-delivery systems as effective strategies for the treatment of CVDs. Full article

The discovery and development of first-in-class (FIC) drugs are becoming increasingly important due to increasing reimbursement pressure and personalized medication. To investigate the technological trends and origin of FIC drugs, the FIC drugs approved in the U.S. from January 2011 to December 2022 were analyzed. The analysis shows that previous major target families, viz. enzymes, G-protein coupled receptors, transporters, and transcription factors, are no longer considered major in recent years. Instead, the shares of secreted proteins/peptides and mRNAs have continuously increased from 2011–2014 to 2019–2022, suggesting that the target family of FIC drugs has shifted to molecules previously considered challenging as drug targets. Small molecules were predominant in 2011–2014, followed by a large increase in antibody medicines in 2015–2018 and further diversification of antibody medicine modalities in 2019–2022. Nucleic acid medicine has also continuously increased its share, suggesting that diversifying modalities supports the creation of FIC drugs toward challenging target molecules. Over half of FIC drugs were created by small and medium enterprises (SMEs), especially young companies established in the 1990s and 2000s. All SMEs that produced more than one FIC drug approved in 2019–2022 have the strong technological capability in a specific modality. Investment in modality technologies and facilitating mechanisms to translate academic modality technologies to start-ups might be important for enhancing FIC drug development. Full article