A highly tuneable inverse emulsion polymerization for the synthesis of stimuli-responsive nanoparticles for biomedical applications.

Polymeric nanomaterials have seen widespread use in biomedical applications as they are highly tuneable to achieve the desired stimuli-responsiveness, targeting, biocompatibility, and degradation needed for fields such as drug delivery and biosensing. However, adjustments to composition and the introduction of new monomers often necessitate reoptimization of the polymer synthesis to achieve the target parameters. In this study, we explored the use of inverse emulsion polymerization to prepare a library of polymeric nanoparticles with variations in pH and temperature response and examined the impact of overall batch volume and the volume of the aqueous phase on nanoparticle size and composition. We were able to prepare copolymeric nanoparticles using three different nonionic and three different anionic comonomers. Varying the non-ionizable comonomers, acrylamide (AAm), 2-hydroxyethyl methacrylate, and N-isopropylacrylamide (NIPAM), was found to alter the mass percentage of methacrylic acid (MAA) incorporated (from 26.7 ± 3.5 to 45.8 ± 1.8 mass%), the critical swelling pH (from 5.687 ± 0.194 to 6.637 ± 0.318), and the volume swelling ratio (from 1.389 ± 0.064 to 2.148 ± 0.037). Additionally, the use of NIPAM was found to allow for temperature-responsive behavior. Varying the ionizable comonomers, MAA, itaconic acid, and 2-acrylamido-2-methylpropane sulfonic acid (AMPSA), was found to significantly alter the critical swelling pH and, in the case of AMPSA, remove the pH-responsive behavior entirely. Finally, we found that for the base P(AAm-co-MAA) formulation, the pH-responsive swelling behavior was independent of the scale of the reaction; however, variations in the aqueous volume relative to the volume of the continuous phase significantly affected both the nanoparticle size and the critical swelling pH.

Stimuli-responsive self-assembled polymer nanoparticles for the oral delivery of antibodies.

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.

Recent Advances in Smart Biomaterials for the Detection and Treatment of Autoimmune Diseases.

Autoimmune diseases are a group of debilitating illnesses that are often idiopathic in nature. The steady rise in the prevalence of these conditions warrants new approaches for diagnosis and treatment. Stimuli-responsive biomaterials also known as "smart", "intelligent" or "recognitive" biomaterials are widely studied for their applications in drug delivery, biosensing and tissue engineering due to their ability to produce thermal, optical, chemical, or structural changes upon interacting with the biological environment. This critical analysis highlights studies within the last decade that harness the recognitive capabilities of these biomaterials towards the development of novel detection and treatment options for autoimmune diseases.

Engineered microscale hydrogels for drug delivery, cell therapy, and sequencing.

Engineered microscale hydrogels have emerged as promising therapeutic approaches for the treatment of various diseases. These microgels find wide application in the biomedical field because of the ease of injectability, controlled release of therapeutics, flexible means of synthesis, associated tunability, and can be engineered as stimuli-responsive. While bulk hydrogels of several length-scale dimensions have been used for over two decades in drug delivery applications, their use as microscale carriers of drug and cell-based therapies is relatively new. Herein, we critically summarize the fundamentals of hydrogels based on their equilibrium and dynamics of their molecular structure, as well as solute diffusion as it relates to drug delivery. In addition, examples of common microgel synthesis techniques are provided. The ability to tune microscale hydrogels to obtain controlled release of therapeutics is discussed, along with microgel considerations for cell encapsulation as it relates to the development of cell-based therapies. We conclude with an outlook on the use of microgels for cell sequencing, and the convergence of the use of microscale hydrogels for drug delivery, cell therapy, and cell sequencing based systems.