Sridhar Kota

Direct delivery of Messenger RNA (mRNA) via inhalation to the lungs could revolutionize the treatment of various pulmonary diseases. By utilizing the target's cellular machinery to produce therapeutic proteins, this approach bypasses the challenges and side effects associated with traditional systemic administration. This non-invasive approach holds the potential to improve the treatment of genetic and infectious pulmonary diseases. This study aimed at the development of Chitosan-tripolyphosphate (CS-TPP) nanoparticles, known for their biocompatibility and the ability to encapsulate nucleic acids, as a means for inhalation delivery of mRNA. The study established an in-house, cost-effective approach for mRNA extraction. The mRNA-incorporated CS-TPP nanoparticles (NPs) were prepared using ionotropic gelation with two formulation approaches based on differing concentrations of chitosan and chitosan to mRNA (w/w) ratios. These NPs were characterized by their particle size and encapsulation efficiencies. Aerodynamic properties were assessed using a vibrating mesh nebulizer and passing through a Next-generation impactor, revealing optimal aerodynamic diameters between 1-5 µm. Transfection efficiency and cellular uptake were evaluated in lung adenocarcinoma (A549) and epithelial (BEAS-2b) cell lines, with protein expression monitored via Confocal imaging. Immunogenicity studies indicated a dose-dependent cytokine release, which could be pivotal for therapeutic outcomes. These findings underscore the potential of CS-TPP mRNA NPs in pulmonary drug delivery systems. The study successfully developed and characterized CS-TPP nanoparticles for inhalable mRNA delivery. These nanoparticles demonstrated successful aerosolization, cellular uptake, and protein expression. Further research is required to optimize nebulization parameters and chitosan-mediated immunogenicity to ultimately enhance safety and therapeutic potential for clinical development.

Though they are compliant, nimble and morpho-logically intelligent, fluidic soft robots often rely on bulky components for power and actuation. This work contributes a design methodology which enables development of soft fluidic robots that move in a sequenced fashion, enabling lightweight devices with embodied intelligence. Bezier-curved beams were introduced as a design building block whose antagonistic placement results in Representative Auxetic Element (RAE) that can be patterned on inflatable shells. Kinematics and loading behaviour of these design building blocks were studied through Finite Element Analysis (FEA). We give a methodology for patterning RAEs on cylindrical and conic shells to create soft fluidic components that move (motion components) and those that delay fluid flow (pinch components). We verify the physical concepts governing the design methodology through two prototype devices that produce sequenced motion under a single fluidic input. Devices using this framework have the potential to perform complicated sequenced motions with lightweight control components.

A pivotless compliant structure is disclosed that can be used to increase the geometric advantage or mechanical advantage of a microelectromechanical (MEM) actuator such as an electrostatic comb actuator, a capacitive-plate electrostatic actuator, or a thermal actuator. The compliant structure, based on a combination of interconnected flexible beams and cross-beams formed of one or more layers of polysilicon or silicon nitride, can provide a geometric advantage of from about 5:1 to about 60:1 to multiply a 0.25-3 .mu.m displacement provided by a short-stroke actuator so that such an actuator can be used to generate a displacement stroke of about 10-34 .mu.m to operate a ratchet-driven MEM device or a microengine. The compliant structure has less play than conventional displacement-multiplying devices based on lever arms and pivoting joints, and is expected to be more reliable than such devices. The compliant structure and an associated electrostatic or thermal actuator can be formed on a common substrate (e.g. silicon) using surface micromachining.