BME Summer Seminar - July 24
Nanomaterials are widely used in a range of biomedical applications such as drug delivery, diagnostics and tissue engineering. Poly-N-isopropylacrylamide (NIPAm) is a well known thermoresponsive polymer systems due to its physiologically relevant lower critical solution temperature (LCST) between 31 and 33°C. Below the LCST poly(NIPAm) is water-soluble, which results in nanoparticle swelling with a coincident increase in water content. Above the LCST, the water is expelled as the poly(NIPAm) collapses on itself and entraps diffusible species inside. This property allows poly(NIPAm) to be quickly loaded with a drug by passive diffusion at temperatures below the LCST and slowly release the drug after the nanoparticles collapse above the LCST. Because of its revesible phase transition, NIPAm has been widely used in the preparation of stimuli responsive systems for biomedical applications, such as in the controlled release of drugs and in tissue engineering.
Prior work by our laboratory has demonstrated that MK2 inhibitor peptide (KAFAK) encapsulated in NIPAm nanoparticles was shielded from peptide degradation in serum. Poly(NIPAm) polymer with nondegradable crosslinker can be loaded by diffusion with up to 60% mass/mass of the cell-penetrating peptide mitogen-activated protein kinase-activated protein kinase 2 (MK2) inhibitor with an amino acid sequence KAFAKLAARLYRKALARQLGVAA (abbreviated KAFAK). However, we also found that only approximately 20% of the KAFAK entrapped inside the inner cores of the NIPAm polymer with nondegradable crosslinker (MBA) were released after 21 days.
In this study, we investigated the use of hydrolytically pH sensitive degradable cross-links to allow the majority of the KAFAK to release from the nanoparticles as the particles degrade. This study has demonstrated that incorporation of polyethylene glycol and various biodegradable crosslinker into traditional NIPAm nanoparticles presents a parameter for size, degradation kinetics, cellular uptake, peptide loading potential and control release potential. This synthesis results in a thermosensitive anionic nanoparticle system that is a potentially useful platform to deliver cationic MK2 inhibitor peptides onto inflammatory disease model.
Bring a sandwich (or equivalent) to seminar – BMEGSA will provide sides, desserts, and drinks.
~This is the last seminar of Summer 2013.~