Senior PharmAssist: Decreased Hospital Use with Enrollment in an Innovative Community-Based Program

OBJECTIVES: To evaluate changes in acute health services use of Senior PharmAssist participants. DESIGN: Retrospective analysis. SETTING: Community-based, nonprofit program in Durham County, North Carolina. PARTICIPANTS: Adults aged 60 and older with income of 200% of the federal poverty level or less who enrolled in the Senior PharmAssist program (N = 191) between August 1, 2011, and March 15, 2017. INTERVENTION: Medication therapy management (MTM), customized community referrals, Medicare insurance counseling, and medication copayment assistance provided by Senior PharmAssist. MEASUREMENTS: Primary outcomes were self-reported emergency department (ED) visits and hospital admissions in the previous year, assessed at baseline and every 6 months for up to 2 years. RESULTS: Mean number of ED visits declined over time (0.83 visits per year at baseline to 0.53 visits per year at 24 months, P = .002), as did the percentage of participants reporting an ED visit in the past year (49% at baseline to 31% at 24 months, P = .003). Mean hospital admissions also decreased (0.56 admissions per year at baseline to 0.4 admissions per year at 24 months, P = .02). There was no significant change in percentage of participants reporting a hospital admission in the past year (33% at baseline to 25% at 24 months, P = .23). CONCLUSION: Older adults who enrolled in a community-based program that helps them manage medications, connect with community resources, and overcome barriers to medication access experienced reductions in acute health services use

Overcoming anti-PEG antibody mediated accelerated blood clearance of PEGylated liposomes by pre-infusion with high molecular weight free PEG

Antibodies that specifically bind polyethylene glycol (PEG), i.e. anti-PEG antibodies (APA), are associated with reduced efficacy and increased risk of serious adverse events for several PEGylated therapeutics. Here, we explored the concept of using free PEG molecules to saturate circulating APA. Surprisingly, we found that 40 kDa free PEG effectively restored the prolonged circulation of PEGylated liposomes in the presence of high titers of pre-existing APA for at least 48 hours in mice. In contrast, lower molecular weight free PEG (≤ 10 kDa) failed to restore circulation beyond a few hours. These in vivo results were consistent with estimates from a minimal physiologically based pharmacokinetic model. Importantly, the infusion of free PEG appeared to be safe in mice previously sensitized by injection of PEGylated liposomes, and free PEG did not elicit excess APA production even in mice with pre-existing adaptive immunity against PEG. Our results support further investigation of high molecular weight free PEG as a potential method to control and overcome high titers of APA, restoring the prolonged circulation of PEGylated liposomes and possibly other PEGylated therapeutics

Minibeam radiation therapy enhanced tumor delivery of PEGylated liposomal doxorubicin in a triple-negative breast cancer mouse model

Background: Minibeam radiation therapy is an experimental radiation therapy utilizing an array of parallel submillimeter planar X-ray beams. In preclinical studies, minibeam radiation therapy has been shown to eradicate tumors and cause significantly less damage to normal tissue compared to equivalent radiation doses delivered by conventional broadbeam radiation therapy, where radiation dose is uniformly distributed. Methods: Expanding on prior studies that suggested minibeam radiation therapy increased perfusion in tumors, we compared a single fraction of minibeam radiation therapy (peak dose:valley dose of 28 Gy:2.1 Gy and 100 Gy:7.5 Gy) and broadbeam radiation therapy (7 Gy) in their ability to enhance tumor delivery of PEGylated liposomal doxorubicin and alter the tumor microenvironment in a murine tumor model. Plasma and tumor pharmacokinetic studies of PEGylated liposomal doxorubicin and tumor microenvironment profiling were performed in a genetically engineered mouse model of claudin-low triple-negative breast cancer (T11). Results: Minibeam radiation therapy (28 Gy) and broadbeam radiation therapy (7 Gy) increased PEGylated liposomal doxorubicin tumor delivery by 7.1-fold and 2.7-fold, respectively, compared to PEGylated liposomal doxorubicin alone, without altering the plasma disposition. The enhanced tumor delivery of PEGylated liposomal doxorubicin by minibeam radiation therapy is consistent after repeated dosing, is associated with changes in tumor macrophages but not collagen or angiogenesis, and nontoxic to local tissues. Our study indicated that the minibeam radiation therapy’s ability to enhance the drug delivery decreases from 28 to 100 Gy peak dose. Discussion: Our studies suggest that low-dose minibeam radiation therapy is a safe and effective method to significantly enhance the tumor delivery of nanoparticle agents