The increase in LMWS was confirmed to be a result of silk solubilizing over time (data not shown). hydration resistance, which are controlled by silk matrix chemistry, peptide domain name distribution and protein density. Secondary ionic repulsions are also crucial in antibody stabilization and release. Matrix modification by free methionine incorporation was found to be an effective strategy for mitigating encapsulation induced antibody oxidation. Additionally, these studies spotlight a characterization approach to improve the understanding and development of other protein sustained delivery systems, with broad applicability to the rapidly developing monoclonal antibody field. Keywords:Protein, Antibody, Stability, Sustained delivery, Silk, Hydrogel == 1. Introduction == Sustained local delivery of drugs offers many advantages over systemic delivery. The most obvious advantage is the potential for improved efficacy, by maintaining drug levels within the therapeutic window for longer periods of time [1]. Also, delivering drugs directly to the disease site eliminates the dependence on physiological targeting mechanisms and provides higher levels of therapeutic available at the targeted site [2,3]. Monoclonal antibodies are excellent therapeutic targets due to their specificity, modular structure, ability to leverage the patients own immune system, and ability to deliver a toxic payload [4-6]. Antibody based therapies are being developed for a wide range of indications in oncology, inflammation, immune mediated disorders, and wound healing [7]. Long-term repetitive dosing is usually common for antibody therapies, therefore drug efficacy and patient compliance would benefit significantly from the availability of sustained local delivery options [7]. While numerous systems and devices are available for sustained local delivery of small molecule therapeutics, none currently exist for monoclonal antibodies despite their broad therapeutic appeal [8]. The limited availability of sustained local delivery systems for antibody therapeutics can be attributed to two factors: material/processing incompatibility with proteins and a flawed development approach. First, the challenges in manufacturing inherently unstable protein therapeutics are exaggerated if a combination therapy is being Etomoxir (sodium salt) developed [8]. The materials and processing strategies commonly used for engineering delivery systems for Etomoxir (sodium salt) proteins have drawbacks, limiting their power. Organic solvents, chemical cross-linking brokers, pH extremes, mechanical stress, and acidic degradation products are frequently required or are present [9-11]. While often acceptable for small molecule therapeutics, these processing strategies are typically incompatible with relatively fragile protein therapeutics [12,13]. Second, and perhaps more importantly, there are limitations to the approach employed for development of combination Etomoxir (sodium salt) products, namely the impartial development and optimization paths for protein therapeutic and delivery matrices. Each product itself is usually complex and unique, requiring years of characterization, optimization, and engineering. It is unlikely that an after-the-fact merging Etomoxir (sodium salt) of a protein therapeutic with an off-the-shelf delivery matrix would be successful. Considering the nuances of each product, incompatibilities and instabilities emerge. The ideal approach would involve co-development of a protein therapeutic with its intended delivery matrix. In this approach, as incompatibilities or instabilities are identified, opportunities exist for matrix or Etomoxir (sodium salt) protein optimization to improve the probability of success. Also, the nature of antibody-matrix interactions must be thoroughly comprehended in order to optimize release profiles. The delivery matrix should be optimized for a specific protein therapeutic and vice versa. While there are many types of biomaterials potentially useful for the above needs, silk fibroin has the potential to address some of these limitations. Silk fibroin is a naturally occurring protein polymer which can be processed into a wide range of useful biomaterial formats including sponges, films, micro/nanoparticles, coatings and hydrogels with a high degree of control of structure and morphology [14]. The use of silk fibroin as a versatile biomaterial, specifically its biocompatibility, all aqueous and ambient manufacturing process, controllable degradation rates, impressive mechanical properties and favorable immunological properties PPIA are well documented [14-17]. Specifically, silk-based materials have been successfully used for sustained small molecule and protein delivery in addition to enzyme, antibiotic, and vaccine stabilization [18-24]. The studies presented here demonstrate the criticality of thorough antibody-matrix conversation characterization. Recently, silk fibroin lyogels, a novel matrix for sustained local delivery of monoclonal antibodies, was described [25]. In order to engineer silk lyogels to optimize antibody release profiles, recovery and stability, insight into the mechanisms regulating silkantibody and silk-solvent relationships was required. Such insights present to help expand refine this delivery and stabilization protocol for antibodies in silk matrices. The current function describes some mechanistic research on antibody packed silk lyogels. The partnership between silk denseness, hydration behavior, and antibody recovery was characterized and confirmed. Release studies had been utilized to characterize the type of silk-antibody relationships, a surfactant was utilized to judge the part of hydrophobic relationships.