ABSTRACT
Currently, commercially available antibody therapies must be delivered via parenteral administration. Oral delivery of antibodies could increase patient compliance and improve quality of life, however there is currently no viable system for delivering antibodies orally. In this work, a self-assembled, pH-responsive nanoparticle delivery system was developed to load and deliver antibodies via the oral route. The nanoparticles were synthesized via nanoprecipitation using the pH-responsive copolymers based on poly(methacrylic acid-co-methyl methacrylate)-block-poly(ethylene glycol). The reversibly hydrophobic nature of this polymer allowed it to function as an antibody delivery system via self-assembly. Characteristics of the polymer, including monomer ratios and molecular weight, as well as parameters of the nanoprecipitation process were optimized using Design of Experiments to achieve nanoparticles with desired size, polydispersity, loading efficiency, and release characteristics. Ultimately, the synthesized and optimized nanoparticles exhibited a hydrodynamic size within a range that avoids premature clearance, a low polydispersity index, and high IgG loading efficiency. In in vitro antibody release studies at physiologically relevant pH values, the nanoparticles exhibit promising release profiles. The nanoparticles presented in this work show potential as oral delivery vehicles for therapeutic antibodies.
Subject(s)
Nanoparticles , Polymers , Humans , Polymers/chemistry , Quality of Life , Polyethylene Glycols/chemistry , Micelles , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Drug Delivery Systems , Drug Carriers/chemistryABSTRACT
The field of biomaterials has advanced significantly in the past decade. With the growing need for high-throughput manufacturing and screening, the need for modular materials that enable streamlined fabrication and analysis of tissue engineering and drug delivery schema has emerged. Microparticles are a powerful platform that have demonstrated promise in enabling these technologies without the need to modify a bulk scaffold. This building block paradigm of using microparticles within larger scaffolds to control cell ratios, growth factors and drug release holds promise. Gelatin microparticles (GMPs) are a well-established platform for cell, drug and growth factor delivery. One of the challenges in using GMPs though is the limited ability to modify the gelatin post-fabrication. In the present work, we hypothesized that by thiolating gelatin before microparticle formation, a versatile platform would be created that preserves the cytocompatibility of gelatin, while enabling post-fabrication modification. The thiols were not found to significantly impact the physicochemical properties of the microparticles. Moreover, the thiolated GMPs were demonstrated to be a biocompatible and robust platform for mesenchymal stem cell attachment. Additionally, the thiolated particles were able to be covalently modified with a maleimide-bearing fluorescent dye and a peptide, demonstrating their promise as a modular platform for tissue engineering and drug delivery applications.
ABSTRACT
The aim of our study was to identify potential critical levels of implantation of an osseointegrated prosthesis for above-knee amputees. The implant used was the OPRA system. It was inserted in the femur at four different amputation heights, characterized by their residual limb ratios (0.299, 0.44, 0.58 and 0.73). The stress and strain distribution was evaluated in the bone-implant system during walking, considering a body mass of 100 kg. Considerably high stimulus (11,489 µÎµ) in the tissue near the tip was found at the highest implantation level. All models presented small non-physiologic stress values in the tissue around the implant. The results revealed that the implantation level has a decisive effect on bone-implant performance. Mainly, the analysis indicates adverse biomechanical conditions for implantations in very short residual limbs.
