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Antibody therapeutics are limited in treating brain diseases due to poor blood-brain barrier (BBB) penetration. We have discovered that poly 2-methacryloyloxyethyl phosphorylcholine (PMPC), a biocompatible polymer, effectively facilitates BBB penetration via receptor-mediated transcytosis and have developed a PMPC-shell-based platform for brain delivery of therapeutic antibodies, termed nanocapsule. Yet, the platform results in functional loss of antibodies due to epitope masking by the PMPC polymer network, which necessitates the incorporation of a targeting moiety and degradable crosslinker to enable on-site antibody release. In this study, we developed a novel platform based on site-oriented conjugation of PMPC to the antibody, allowing it to maintain key functionalities of the original antibody. With an optimized PMPC chain length, the PMPC-antibody conjugate exhibited enhanced brain delivery while retaining epitope recognition, cellular internalization, and antibody-dependent cellular phagocytic activity. This simple formula incorporates only the antibody and PMPC without requiring additional components, thereby addressing the issues of the nanocapsule platform and paving the way for PMPC-based brain delivery strategies for antibodies.

 

With the increasing interest in biopolymer nanofibers for diverse applications, the characterization of these materials in the physiological environment has become of equal interest and importance. This study performs first‐time simulated body fluid (SBF) degradation and tensile mechanical analyses of blended fish gelatin (FGEL) and polycaprolactone (PCL) nanofibrous meshes prepared by a high‐throughput free‐surface alternating field electrospinning. The thermally crosslinked FGEL/PCL nanofibrous materials with 84–96% porosity and up to 60 wt% PCL fraction demonstrate mass retention up to 88.4% after 14 days in SBF. The trends in the PCL crystallinity and FGEL secondary structure modification during the SBF degradation are analyzed by Fourier transform infrared spectroscopy. Tensile tests of such porous, 0.1–2.2 mm thick FGEL/PCL nanofibrous meshes in SBF reveal the ultimate tensile strength, Young's modulus, and elongation at break within the ranges of 60–105 kPa, 0.3–1.6 MPa, and 20–70%, respectively, depending on the FGEL/PCL mass ratio. The results demonstrate that FGEL/PCL nanofibrous materials prepared from poorly miscible FGEL and PCL can be suitable for selected biomedical applications such as scaffolds for skin, cranial cruciate ligament, articular cartilage, or vascular tissue repair.