Native PLGA nanoparticles attenuate Aß-seed induced tau aggregation under in vitro conditions: potential implication in Alzheimer's disease pathology.

Evidence suggests that beta-amyloid (Aß)-induced phosphorylation/aggregation of tau protein plays a critical role in the degeneration of neurons and development of Alzheimer's disease (AD), the most common cause of dementia affecting the elderly population. Many studies have pursued a variety of small molecules, including nanoparticles conjugated with drugs to interfere with Aß and/or tau aggregation/toxicity as an effective strategy for AD treatment. We reported earlier that FDA approved PLGA nanoparticles without any drug can attenuate Aß aggregation/toxicity in cellular/animal models of AD. In this study, we evaluated the effects of native PLGA on Aß seed-induced aggregation of tau protein using a variety of biophysical, structural and spectroscopic approaches. Our results show that Aß1-42 seeds enhanced aggregation of tau protein in the presence and absence of heparin and the effect was attenuated by native PLGA nanoparticles. Interestingly, PLGA inhibited aggregation of both 4R and 3R tau isoforms involved in the formation of neurofibrillary tangles in AD brains. Furthermore, Aß seed-induced tau aggregation in the presence of arachidonic acid was suppressed by native PLGA. Collectively, our results suggest that native PLGA nanoparticles can inhibit the Aß seed-induced aggregation of different tau protein isoforms highlighting their therapeutic implication in the treatment of AD.

The Impact of Free Radical Stabilization Techniques on in vivo Mechanical Changes in Highly Cross-Linked Polyethylene Acetabular Liners.

INTRODUCTION: Numerous thermal free radical stabilization techniques are used in the production of highly cross-linked polyethylene (HXLPE) to improve oxidative stability. Little knowledge exists on the effects of in vivo time on the mechanical properties of HXLPE. The purpose of this study was to determine if free radical stabilization of HXLPE impacts mechanical properties as well as oxidative stability of acetabular liner rims after extended in vivo time. METHODS: Retrieved and control remelted, single annealed and sequentially annealed HXLPE liner rims were tested for mechanical properties. Oxidation was measured with FTIR spectroscopy and crystalline phase composition measured with Raman spectroscopy. RESULTS: No correlation was found between in vivo, ex vivo time and hardness for annealed groups. A statistically significant difference in hardness was identified between free radical stabilization groups. No correlation between maximum rim oxidation and in vivo time was found. Detectable levels of rim oxidation were present in 100% of single annealed, 75% of sequentially annealed, and 25% of remelted retrieved liners. Single and sequentially annealed liners demonstrated oxidation and increased crystallinity. Rim mechanical properties change in vivo for implant types. With in vivo time, retrieved remelted HXLPE demonstrated decreased mechanical properties, whereas retrieved single and sequentially annealed HXLPE properties remained stable. All liner cohorts demonstrated evidence of rim oxidation. Subsequent changes in crystallinity were only observed in oxidized annealed liners. CONCLUSION: HXLPE acetabular liner rims show evidence of in vivo mechanical property degradation, notably in remelted HXLPE, which may be a risk factor in rim fracture and catastrophic implant failure.