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.

Circumferential adjustment of ultrasound probe position to determine the optimal approach to the internal jugular vein: a noninvasive geometric study in adults.

Circumferential adjustment of the position of a two-dimensional ultrasound (US) probe around the neck has been recommended as a strategy for reducing the potential for unintentional common carotid artery puncture during internal jugular venous (IJV) cannulation. We obtained multiple high-resolution US images bilaterally from the necks of 107 adult subjects and analyzed these to determine the degree to which this strategy permits identification of a pathway from the skin to the IJV that minimizes venoarterial overlap while maximizing venous target (angular) width. The method consistently permitted identification of an approach to the IJV superior to that obtainable with any one of four popular surface anatomy-based ("blind") approaches and was even more powerful if used in concert with a US-guided 1) adjustment of the degree of head rotation, 2) choice between a high and low approach, and 3) choice between the right and left IJV. Use of a high-resolution US imaging device also permitted identification of the precise boundaries of additional cervical anatomic structures (nontarget vessels, lymph nodes, and the thyroid gland) potentially relevant to selection of an optimal approach to the IJV.