Journal of Controlled Release最新文献

Acute kidney injury (AKI) represents a rapid decline in kidney function, often associated with significant morbidity and mortality. Inefficient management of acute-phase inflammation and inadequate repair of established damage exacerbate AKI and facilitate its progression to chronic kidney disease (CKD). Platelet membrane (PM) has emerged as a promising targeting ligand in various studies. PM proteins can also facilitate the recruitment and differentiation of CD34⁺ cells (hematopoietic stem cells and endothelial progenitor cells) through both direct and indirect mechanisms, including enhancing adhesion of CD34⁺ cells to damaged tissues and elevating stromal cell-derived factor-1 (SDF-1) levels in ischemia-reperfusion injury (IRI) kidneys. In parallel, extensive research has demonstrated that rapamycin shows high potential as an anti-inflammatory therapy for AKI. Herein, we design a PM hybrid rapamycin liposome (Rapa@PM-Lipo), which not only improves the delivery efficiency of rapamycin, but also leverages the potential of PM to achieve long-lasting repair. Rapa@PM-Lipo significantly reduced Acute renal Tubular Necrosis (ATN) score in IRI kidneys following intravenous administration, both as a single and multiple doses. This study exploits the therapeutic potential of PM and explores its novel applications for facilitating tissue repair, presenting a promising strategy for the treatment of AKI and mitigating its progression to CKD.

Predicting the release performance of subcutaneous (SC) drug formulations is challenging due to the complex interplay between physicochemical properties and the physiological microenvironment, which includes the extracellular matrix (ECM), fluid composition, and fluid availability, factors that collectively influence bioavailability and absorption rates. The ECM often acts as a bandpass filter modulated by local ion and protein content. In this study, we introduce the BioJect cell, a modern release test method based on the compendial flow-through cell, integrating a perfusion system with customizable biomatrix components. We systematically investigated the release mechanisms of four insulin formulations: regular human insulin, insulin aspart, insulin glulisine, and Neutral Protamine Hagedorn (NPH) insulin. A modified simulated subcutaneous interstitial fluid (mSSIF) comprising multiple components of the SC physiological environment was employed. It incorporates important ions and proteins (138.5 mM sodium, 10 mM potassium, 1.8 mM calcium, 0.8 mM magnesium, 111.3 mM chloride, 28 mM bicarbonate, 0.5 mM sulfate, 5 mM acetate, 4.2 mM phosphate, 30 g/L total protein added as bovine serum albumin). Our release test method discriminated the tested formulations under varying biorelevant conditions, demonstrating its biopredictive capabilities. Notably, we discovered a previously undocumented albumin binding affecting the release rate of insulin glulisine, likely occurring in the low-shear environment of SC tissue only. Additionally, the inclusion of biorelevant components like hyaluronic acid and collagen into the biomatrix of the BioJect cell provided profound insights into potential absorption and release mechanisms, supported by two in vitro-in vivo relationships (level C and level A). The BioJect cell represents a significant advancement in simulating the SC environment for drug release testing. Our findings highlight the importance of considering protein binding and ECM components in predicting drug absorption, offering a promising tool for the development and optimization of SC formulations.

Although there are many challenges in using nanobodies for treating various complex tumor diseases, including rapid renal clearance and the complex blood-brain barrier environment, nanobodies have shown great potential due to their high antigen affinity, excellent tumor penetration ability, and favorable safety profile. Since the discovery of the variable domain (VHH) of camelid heavy-chain antibodies in 1993, nanobodies have been progressively applied to various cancer therapy platforms, such as antagonistic drugs and targeting agents for effector domains. In recent years, several nanobody-based drugs, including Caplacizumab, KN-035, and Ozoralizumab, have been approved for clinical use. Among them, KN-035 is used for treating advanced solid tumors, and these advancements have propelled nanobody development to new heights. Currently, nanobodies are being rapidly applied to the treatment of a wide range of diseases, from viral infections to cancer, demonstrating strong advantages in areas such as targeted protein degradation, bioimaging, nanobody-drug conjugation, bispecific T-cell engagers, and vaccine applications. Bibliometric tools, including CiteSpace, HisCite Pro, and Alluvial Generator, were employed to trace the historical development of nanobodies in cancer research. The contributions of authors, countries, and institutions in this field were analyzed, and research hotspots and emerging trends were identified through keyword analysis and influential articles. Future trends were also predicted. This study provides a unique, comprehensive, and objective perspective on the use of nanobodies in tumor research, laying a foundation for future research directions and offering valuable insights for researchers in the field.