Simultaneous optimization of cisplatin-loaded PLGA-mPEG nanoparticles with regard to their size and drug encapsulation

A central composite experimental design was applied to investigate the effect of five preparative variables on the size and cisplatin encapsulation efficiency of poly(lactide-co-glycolide)-methoxy poly(ethylene glycol) (PLGA-mPEG) nanoparticles. The nanoparticles were prepared by a nano-precipitation process and were characterized with regard to their morphology by scanning electron microscopy, their size by photon correlation spectroscopy and their drug content by atomic absorption spectroscopy respectively. The preparative variables investigated were: solids concentration, aqueous to organic phase volume ratio, temperature, rate of organic phase addition in aqueous phase and agitation. The nanoparticles prepared in this study appeared to be spherical and rather homogeneous in size under the scanning electron microscope. The size and the drug encapsulation of the prepared nanoparticles ranged between 90-180 nm and 0%-40%, respectively. The fitted model could adequately describe the experimental data. The statistical analysis showed that all preparative variables studied, except temperature, affected significantly both the size and the drug loading of nanoparticles. The size was most affected by the agitation whereas the loading was most affected by the phase ratio. Significant interactions between the preparative variables were also observed. The "desirability function" approach was applied to simultaneously optimize the nanoparticles with regard to their size and cisplatin encapsulation. The predictive power of the applied model was more satisfactory in the case of nanoparticles size than with cisplatin encapsulation efficiency. It appears to be feasible to select optimum conditions for the preparation of PLGA-mPEG nanoparticles of cisplatin based on a central composite design and the "desirability function" optimization approach. © 2008 Bentham Science Publishers Ltd

Economic evaluation of trimetazidine in the management of chronic stable angina in Greece

Background: To evaluate the cost-effectiveness of trimetazidine (TMZ) as add-on therapy to standard-of-care (SoC) compared to SoC alone in patients with chronic stable angina who did not respond adequately to first line therapy with b-blockers, nitrates or calcium channel antagonists in Greece. Methods: A Markov model with 3-month cycles and 1-year time horizon was developed to assess the comparators. The analysis was conducted from a third-party payer perspective. The clinical inputs and utility values were extracted from the published literature. Resource consumption data were obtained from local experts, using a questionnaire developed for the purpose of the study and were combined with unit cost data (in €2016) obtained from official sources. Cost effectiveness was assessed by calculating the incremental cost effectiveness ratio (ICER). Probabilistic sensitivity analysis (PSA) was performed to account for uncertainty and variation in the input parameters of the model. Results: The analysis showed that the cost of TMZ plus SoC was €1755.57 versus €1751.76 of SoC alone. In terms of health outcomes, TMZ plus SoC was associated with 0.6650 QALYs versus 0.6562 QALYs for SoC alone. The incremental analysis resulted in an ICER of €430.67 per QALY gained. PSA revealed that the probability of TMZ plus SoC being cost-effective over SoC was 89 %, at a threshold of €34,000 per QALY gained. Conclusion: The results indicate that TMZ as add -on treatment may be a highly cost-effective option for the symptomatic treatment of patients with chronic stable angina in Greece relative to SoC alone. © 2016 The Author(s)

Economic evaluation of ivabradine in the treatment of chronic heart failure in Greece

Background: The objective of our study was to assess the cost-effectiveness of ivabradine plus standard care (SoC) in chronic heart failure (CHF) patients with sinus rhythm and a baseline heart rate ≥ 75 b.p.m. in Greece, in comparison with current SoC alone. Methods: An existing cost-effectiveness model consisting of two health states, was adapted to the Greek health care setting. All clinical inputs of the model (i.e. mortality rates, hospitalization rates, NYHA class distribution and utility values) were estimated from SHIFT trial data. All costing data used in the model reflects the year 2013 (in €). An incremental cost effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was calculated. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. The horizon of analysis was over patient life time and both cost and outcomes were discounted at 3.5% per year. The analysis was conducted from a Greek third party-payer perspective. Results: The Markov analysis revealed that the discounted quality-adjusted survival was 4.27 and 3.99 QALYs in the ivabradine plus SoC and SoC alone treatment arms, respectively. The cumulative lifetime total cost per patient was €8,665 and €5,873, for ivabradine plus SoC and SoC alone, respectively. The ICER for ivabradine plus SoC versus SoC alone was estimated as €9,986 per QALY gained. The PSA showed that the likelihood of ivabradine plus SoC being cost-effective at a threshold of €36,000/QALY was found to be 95%. Conclusions: Ivabradine plus SoC may be regarded as a cost-effective option for the treatment in CHF patients in Greece. © 2014 Kourlaba et al.; licensee BioMed Central Ltd

ECONOMIC EVALUATION OF TRIMETAZIDINE IN THE MANAGEMENT OF CHRONIC STABLE ANGINA IN GREECE

Background: To evaluate the cost-effectiveness of trimetazidine (TMZ) as add-on therapy to standard-of-care (SoC) compared to SoC alone in patients with chronic stable angina who did not respond adequately to first line therapy with b-blockers, nitrates or calcium channel antagonists in Greece. Methods: A Markov model with 3-month cycles and 1-year time horizon was developed to assess the comparators. The analysis was conducted from a third-party payer perspective. The clinical inputs and utility values were extracted from the published literature. Resource consumption data were obtained from local experts, using a questionnaire developed for the purpose of the study and were combined with unit cost data (in €2016) obtained from official sources. Cost effectiveness was assessed by calculating the incremental cost effectiveness ratio (ICER). Probabilistic sensitivity analysis (PSA) was performed to account for uncertainty and variation in the input parameters of the model. Results: The analysis showed that the cost of TMZ plus SoC was €1755.57 versus €1751.76 of SoC alone. In terms of health outcomes, TMZ plus SoC was associated with 0.6650 QALYs versus 0.6562 QALYs for SoC alone. The incremental analysis resulted in an ICER of €430.67 per QALY gained. PSA revealed that the probability of TMZ plus SoC being cost-effective over SoC was 89 %, at a threshold of €34,000 per QALY gained. Conclusion: The results indicate that TMZ as add -on treatment may be a highly cost-effective option for the symptomatic treatment of patients with chronic stable angina in Greece relative to SoC alone. © 2016 The Author(s)