Synergetic Effect of rHDL and LXR Agonist on Reduction of Atherosclerosis in Mice.

High-density lipoproteins (HDLs) are unique in that they play an important role in the reverse cholesterol transport process. However, reconstituted HDL (rHDL) infusions have demonstrated limited beneficial effect in clinical practice. This is perhaps a consequence of the limited cholesterol efflux abilities of atheroma macrophages due to decreased expression of cholesterol transporters in advanced atheromas and following rHDL infusion treatment. Thus, we propose that a combination therapy of rHDL and a liver X receptor (LXR) agonist could maximize the therapeutic benefit of rHDL by upregulating ATP-binding cassette transporters A-1 (ABCA1) and ATP-binding cassette transporter G-1 (ABCG1), and enhancing cholesterol efflux to rHDL. In macrophages, rHDL downregulated the expression of ABCA1/G1 in a dose- and rHDL composition-dependent manner. Although LXR agonist, T0901317 (T1317), upregulated the expression of ABCA1 and ABCG1, the drug itself did not have any effect on cholesterol efflux (6.6 ± 0.5%) while the combination of rHDL and T1317 exhibited enhanced cholesterol efflux from [3H]-cholesterol loaded J774A.1 macrophages (23.3 ± 1.3%). Treatment with rHDL + T1317 significantly reduced the area of aortic plaque in ApoE-/- mice compared to PBS treated control animals (24.16 ± 1.42% vs. 31.59 ± 1.93%, p < 0.001), while neither rHDL nor T1317 treatment alone had a significant effect. Together, we show that rHDL paired with an LXR agonist can induce a synergetic effect in reducing atheroma burden. This synergy could lead to lower overall effective dose for both drugs, potentially overcoming the existing barriers in clinical development and renewing pharmaceutical interest in these two drug classes.

An ultraviolet-curable, core-shell vaccine formed via phase separation.

One of the central challenges in the field of vaccine delivery is to develop a delivery method that maintains antigen stability while also enabling control over the system's release kinetics. Addressing these challenges would not only allow for expanded access to vaccines worldwide but would also help significantly reduce mortality rates in developing countries. In this article, we report the development of single-injection vaccine depots for achieving novel delayed burst release. Synthesized poly(ε-caprolactone) and poly(ε-caprolactone) triacrylate were used to form stationary bubbles within an aqueous solution of 10% carboxymethylcellulose. These polymeric bubbles (referred to as "polybubbles") can then be injected with an aqueous solution of cargo, resulting in the formation of a polymeric shell. The puncture resulting from cargo injection self-heals prior to ultraviolet (UV) curing. UV curing and lyophilization were shown to enhance the stability of the polybubbles. BSA- CF 488 and HIV1 gp120/41 were used as the antigen in the study as a proof-of-concept. Further endeavors to automate the production of polybubbles are underway.

Clinically advancing and promising polymer-based therapeutics.

In this review article, we will examine the history of polymers and their evolution from provisional World War II materials to medical therapeutics. To provide a comprehensive look at the current state of polymer-based therapeutics, we will classify technologies according to targeted areas of interest, including central nervous system-based and intraocular-, gastrointestinal-, cardiovascular-, dermal-, reproductive-, skeletal-, and neoplastic-based systems. Within each of these areas, we will consider several examples of novel, clinically available polymer-based therapeutics; in addition, this review will also include a discussion of developing therapies, ranging from the in vivo to clinical trial stage, for each targeted area of treatment. Finally, we will emphasize areas of patient care in need of more effective, accessible, and targeted treatment approaches where polymer-based therapeutics may offer potential solutions.