5 research outputs found
Nanoscaled Poly(l‑glutamic acid)/Doxorubicin-Amphiphile Complex as pH-responsive Drug Delivery System for Effective Treatment of Nonsmall Cell Lung Cancer
Nonsmall cell lung cancer (NSCLC)
is the leading cause of cancer-related death worldwide. Herein, we
develop a polypeptide-based block ionomer complex formed by anionic
methoxy poly(ethylene glycol)-<i>b</i>-poly(l-glutamic
acid) (mPEG-<i>b</i>-PLG) and cationic anticancer drug doxorubicin
hydrochloride (DOX·HCl) for NSCLC treatment. This complex spontaneously
self-assembled into spherical nanoparticles (NPs) in aqueous solutions
via electrostatic interaction and hydrophobic stack, with a high loading
efficiency (almost 100%) and negative surface charge. DOX·HCl
release from the drug-loaded micellar nanoparticles (mPEG-<i>b</i>-PLG-DOX·HCl) was slow at physiological pH, but obviously
increased at the acidic pH mimicking the endosomal/lysosomal environment.
In vitro cytotoxicity and hemolysis assays demonstrated that the block
copolypeptide was cytocompatible and hemocompatible, and the presence
of copolypeptide carrier could reduce the hemolysis ratio of DOX·HCl
significantly. Cellular uptake and cytotoxicity studies suggested
that mPEG-<i>b</i>-PLG-DOX·HCl was taken up by A549
cells via endocytosis, with a slightly slower cellular internalization
and lower cytotoxicity compared with free DOX·HCl. The pharmacokinetics
study in rats showed that DOX·HCl-loaded micellar NPs significantly
prolonged the blood circulation time. Moreover, mPEG-<i>b</i>-PLG-DOX·HCl exhibited enhanced therapeutic efficacy, increased
apoptosis in tumor tissues, and reduced systemic toxicity in nude
mice bearing A549 lung cancer xenograft compared with free DOX·HCl,
which were further confirmed by histological and immunohistochemical
analyses. The results demonstrated that mPEG-<i>b</i>-PLG
was a promising vector to deliver DOX·HCl into tumors and achieve
improved pharmacokinetics, biodistribution and efficacy of DOX·HCl
with reduced toxicity. These features strongly supported the interest
of developing mPEG-<i>b</i>-PLG-DOX·HCl as a valid
therapeutic modality in the therapy of human NSCLC and other solid
tumors
Clopidogrel and Aspirin versus Aspirin Alone for Stroke Prevention: A Meta-Analysis
<div><p>Background and Purpose</p><p>Antiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet therapy, and dual therapy with clopidogrel and aspirin is of particular interest. We conducted this meta-analysis to systematically review studies about dual therapy comparing monotherapy with aspirin alone.</p><p>Methods</p><p>Randomized controlled trials were searched in PubMed (1966-May, 2015), EMBASE (1947-May, 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (1948-May, 2015), WHO International Clinical Trial (ICTRP) (2004-May, 2015), China Biology Medicine disc (CBM disc) (1978-May, 2015) and were included into the final analysis according to the definite inclusion criteria mentioned in the study selection section. Risk ratio (RR) was pooled with 95% confidence interval (CI) for dichotomous data. The heterogeneity was considered significant if the χ<sup>2</sup> test was significant (P value < 0.10) or the I<sup>2</sup> > 50.00%. Subgroup analyses were carried out on the long and short time periods, the race and region.</p><p>Results</p><p>We included 5 studies involving 24,084 patients. A pooled analysis showed that dual therapy with clopidogrel and aspirin had a lower stroke incidence than monotherapy in both the short term and long term (RR = 0.69, 95% CI: 0.59–0.82, P <0.05; RR = 0.84, 95% CI: 0.72–0.98, P = 0.03, respectively). With regard to safety, dual therapy had a higher risk of bleeding than monotherapy for both periods (RR = 1.51, 95% CI: 1.03–2.23, P = 0.04; RR = 1.54, 95% CI: 1.32–1.79, P<0.05, respectively).</p><p>Conclusions</p><p>Dual therapy with clopidogrel and aspirin could be a preferable choice to prevent stroke in patients who have had a previous stroke or transient ischemic attack, as well as those who are at high risk for stroke. And the effect of dual therapy seems to be more obvious for short-term. However, it is associated with a higher risk of bleeding.</p></div
Risk of bias summary for each included study.
<p>Risk of bias summary for each included study.</p