Cornea-Derived Mesenchymal Stromal Cells Therapeutically Modulate Macrophage Immunophenotype and Angiogenic Function.

Macrophages are crucial drivers of inflammatory corneal neovascularization and thus are potential targets for immunomodulatory therapies. We hypothesized that therapeutic use of cornea-derived mesenchymal stromal cells (cMSCs) may alter the function of macrophages. We found that cMSCs can modulate the phenotype and angiogenic function of macrophages. In vitro, cMSCs induce apoptosis of macrophages while preferentially promoting a distinct CD14hi CD16hi CD163hi CD206hi immunophenotype that has significantly reduced angiogenic effects based on in vitro angiogenesis assays. In vivo, application of cMSCs to murine corneas after injury leads to reduced macrophage infiltration and higher expression of CD206 in macrophages. Macrophages cocultured ("educated") by cMSCs express significantly higher levels of anti-angiogenic and anti-inflammatory factors compared with control macrophages. In vivo, injured corneas treated with cMSC-educated macrophages demonstrate significantly less neovascularization compared with corneas treated with control macrophages. Knocking down the expression of pigment epithelial derived factor (PEDF) in cMSCs significantly abrogates its modulating effects on macrophages, as shown by the reduced rate of apoptosis, decreased expression of sFLT-1/PEDF, and increased expression of vascular endothelial growth factor-A in the cocultured macrophages. Similarly, cMSCs isolated from PEDF knockout mice are less effective compared with wild-type cMSCs at inhibiting macrophage infiltration when applied to wild-type corneas after injury. Overall, these results demonstrate that cMSCs therapeutically suppress the angiogenic capacity of macrophages and highlight the role of cMSC secreted PEDF in the modulation of macrophage phenotype and function. Stem Cells 2018;36:775-784.

Labrasol-Enriched Nanoliposomal Formulation: Novel Approach to Improve Oral Absorption of Water-Insoluble Drug, Carvedilol.

The purpose of the current study was to develop a novel liposomal formulation to improve the oral bioavailability of carvedilol, a Biopharmaceutics Classification System class II with poor aqueous solubility and extensive presystemic metabolism. Conventional and various surfactant-enriched carvedilol-loaded liposomes were prepared by thin film hydration technique and physicochemical properties of liposomes (including size, encapsulation efficiency, release behavior, and morphology) were evaluated. To assess the oral bioavailability, in vivo studies were carried out in eight groups of male Wistar rats (n = 6) and the drug plasma concentration was determined. Conventional and surfactant containing liposomes showed average particle size of 76-104 nm with a narrow size distribution, high encapsulation efficiency (80%≤) and a sustained release profile in simulated intestinal fluid. Compared to the suspension, conventional and Labrasol containing liposomes significantly improved the oral bioavailability and peak plasma concentration of carvedilol. Biocompatibility studies (cell cytotoxicity and histopathological analyses) showed that the enhancing effect might be achieved without any apparent toxicity in the intestine. Decreased oral absorption of carvedilol nanovesicles by using a chylomicron flow blocker indicated contribution of lymphatic transport in nanocapsules absorption. The results reported the successful development of biocompatible Labrasol-enriched carvedilol nanoliposomal formulation with a significant oral enhancement capability. Graphical Abstract ᅟ.

Implementation of an Automated Phone Call Distribution System in an Inpatient Pharmacy Setting.

Background: Inpatient pharmacies receive numerous phone calls from health care professionals and patients. This uncaptured workload poses potential staffing concerns for pharmacy administrators as unequal distribution or misdirected calls to the pharmacy team can lead to accountability and patient safety concerns. We aimed to implement and evaluate the effectiveness of an automated call distribution (ACD) system in an inpatient pharmacy setting at a US Department of Veterans Affairs hospital. Observations: A new inpatient pharmacy service phone line extension was implemented at the Edward Hines, Jr. Veterans Affairs Hospital in Illinois. The ACD phone system yielded positive performance metrics, including ≤ 30 seconds mean speed to answer and ≤ 5% abandonment rate in the 12 months after implementation. Conclusions: The ACD phone system is a promising, new application of available technology implemented in a nontraditional setting. The ACD system provides more actionable information and quality metrics data to pharmacy leadership. The implementation of the ACD system has improved accountability, efficiency, work distribution, and the allocation of resources.

The race to a COVID-19 vaccine: opportunities and challenges in development and distribution.

The unprecedented toll of severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus 2019 disease (COVID-19), jumpstarted the race towards the development and distribution of effective treatment and prevention options. With an urgent need to slow viral transmission, lessen disease severity, and reduce mortality, biopharmaceutical companies rapidly began investigating potential COVID-19 vaccinations. While typical vaccine development can take upwards of 10-15 years, COVID-19 vaccines were developed in less than a year after the identification of COVID-19. To accomplish this feat, clinical development, manufacturing scale-up and distribution are occurring in parallel for the four COVID-19 vaccine front-runners. This remarkable opportunity will forever change the drug development process and would not be possible without tremendous dedication from the public and private sectors, researchers, and clinical trial volunteers. However, many challenges still lie ahead. Comprehensive plans for equitable vaccine education, distribution, administration and post-marketing surveillance must be implemented successfully to overcome vaccine hesitancy, supply-chain obstacles and healthcare provider shortages in an already overburdened healthcare system. We are moving forward at a remarkable pace but worldwide immunity through vaccination will take time to achieve. Thus, current prevention efforts of masking, hand hygiene and social distancing must remain in effect for the foreseeable future. We must remain diligent and not fatigue in our efforts. Ending the COVID-19 pandemic cannot rest on the promise of vaccination alone - it will require a continued, robust and multi-faceted approach to disease treatment and prevention.

Effective attenuation of vascular restenosis following local delivery of chitosan decorated sirolimus liposomes.

Assuring the efficient local delivery via biocompatible nanosystems can be considered as a promising therapy for restenosis. The aim of the present study was preparation, in vitro characterization, and in vivo efficacy evaluation of sirolimus containing chitosan decorated liposomes for restenosis treatment. Liposomes were coated with chitosan, leading to ∼38nm increase in the particle size and a positive shift in the zeta potential from -1mV to +21mV. Chitosan modification was also confirmed by TEM, increased stability against detergent solubilization, and FTIR analyses. High entrapment efficiency (≥83%) and sustained release behaviors were demonstrated in both coated and uncoated vesicles. Compared to control groups, treatment of balloon injured rats with uncoated and chitosan-coated liposomes (50µg sirolimus) significantly reduced stenosis by 39% and 62%, respectively. The effect was also confirmed by immunohistochemical and in vivo CT angiography imaging studies. Chitosan-coated liposomes could be a novel platform for restenosis treatment.

Evaluating the effect of Matricaria recutita and Mentha piperita herbal mouthwash on management of oral mucositis in patients undergoing hematopoietic stem cell transplantation: A randomized, double blind, placebo controlled clinical trial.

OBJECTIVES: To investigate the effects of Matricaria recutita and Mentha piperita on oral mucositis (OM) in patients undergoing hematopoietic stem cell transplantation (HSCT). DESIGN: Randomized double blind placebo controlled clinical trial. SETTING: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, and Bone Marrow Transplantation Center at Taleghani Teaching Hospital, Tehran, Iran. PARTICIPANTS: Sixty patients undergoing HSCT were randomly assigned to two groups: placebo (n=33), and herbal mouthwash group (n=27). INTERVENTIONS: All patients received the mouthwash one week before HSCT and were instructed to use it three times daily for at least 30s. MAIN OUTCOME MEASURES: OM was graded using National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale (grade 0-5). The Numerical Rating Scale (NRS: 0-10 scale) measured the severity of OM symptoms. RESULTS: The duration, maximum and average daily grade of OM were significantly reduced in the treatment group (P<0.05). The use of herbal mouthwash led to significant improvements in pain intensity (P=0.009), dryness (P=0.04) and dysphagia (P=0.009). Other significant results included: reduced need for complementary medications (P=0.03), narcotic analgesics (P=0.047), total parenteral nutrition (TPN) (P=0.02) and the duration of TPN (P=0.03). CONCLUSION: This study shows that patients receiving the herbal mouthwash experienced less complications and symptoms associated with OM. In summary, it seems that the use of our prepared herbal mouthwash is beneficial for patients undergoing HSCT.

Effects of Pharmacist Intervention on the Utilization of Vancomycin in a Teaching Hospital.

In order to investigate the effect of pharmacist intervention on vancomycin use, this study was performed on all patients receiving vancomycin in the intensive care unit (ICU) and hematology-oncology ward of Taleghani Educational Hospital in Tehran, Iran. Vancomycin use was assessed during a pre- and post-intervention period in accordance with the Center of Disease Control and prevention (CDC) and Infectious Diseases Society of America (IDSA) guidelines. Following the intervention, there was a significant change in appropriate initiation of vancomycin (P = 0.009) and no significant improvement was observed in adequate dosage and the duration of therapy (P = 0.15 and P = 0.54 respectively); however, informing the physician resulted in discontinuation of the drug in 50% of inappropriate cases and vancomycin dosage was adjustedin 31% of cases. Temperature charts, culture results and pre-treatment CBC tests changed significantly (P = 0.02, P = 0.009 and P = 0.04 respectively). The rate of infusion related adverse drug reactions did not decrease significantly (P = 0.06); yet in 100% of patients, these reactions were resolved after notifying the nursing team. After pharmacist intervention,vancomycin use improved in some aspects. A significant improvement in appropriate initiation of therapy was observed; however, treatments continued despite negative cultures. It is necessary to optimize the use of vancomycin by performing more educational interventions.