Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

Background

Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues.

Methods

PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells.

Results

Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, −11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, −5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg).

Conclusion

In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may represent a promising drug delivery system in cancer therapy.     

Long-term upper and lower urinary tract functions in children with posterior urethral valves

ObjectiveSeveral factors have been identified as predictive of future renal function in children with posterior urethral valves (PUV). Our aim was to analyse upper and lower urinary tract outcome in patients with PUV, and determine any factors from the period of early management that were predictive of future renal function.MethodsThe charts of 67 boys (mean age 2.4 years) diagnosed with PUV were reviewed. The most common presenting symptom was dribbling in 43.2% and UTI in 28.3%. Twenty-three (34.8%) patients developed end-stage renal disease aged 1–15 years. The mean time of renal survival was calculated as 7.8 (SEM = 0.73) years.ResultsIncontinence in patients over 5 years old, lower urinary tract dysfunction, serum creatinine level in first year or at the time of diagnosis, and presence of vesicoureteral reflux and high-grade bilateral reflux were significant risk factors for occurrence of renal failure in the future. Lower tract dysfunction was seen in 58.6% of patients. Postnatal diagnosis and presence of high-grade reflux were significant risk factors for the future occurrence of lower urinary tract dysfunction.ConclusionIt is important to recognize that PUV have consequences not only during childhood or before treatment, but also during or after the treatment period. Long-term assessment and follow-up of upper and lower urinary tract functions after valve ablation is necessary.     

Lack of any Association between the Hogg1 Ser326Cys Polymorphism and Breast Cancer Risk: a Systematic Review And Meta-Analysis Of 18 Studies

Background: The human 8-oxoguanine DNA glycosylase (hOGG1) gene may be linked with cancer susceptibility. The aim of this study was to quantitatively summarize any association between the hOGG1 Ser326Cys polymorphism and breast cancer (BC) risk. Materials and Methods: A comprehensive search of the PubMed, Embase, and ISI web of knowledge databases for papers published before 1 October 2016 was conducted. Summary odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CIs) were estimated, with fixed-effects or random-effects models when appropriate, to assess any association. Results: A total of 9,434 cases and 10,497 controls from 18 studies were included in this meta-analysis. When the eligible studies were pooled, there was no evidence found for a significant association between the hOGG1 Ser326Cys polymorphism and BC in in all genetic contrast models G vs. C (OR=1.19, 95% CI 0.92– 1.53), CG vs. CC (OR = 0.97, 95% CI 0.91-1.04, p = 0.46), GG vs. CC (OR = 1.11, 95% CI 0.91-1.35, p = 0.30), GG + CG vs. CC (OR = 0.98, 95% CI 0.92-1.05, p = 0.67), and GG vs. CG + CC (OR = 1.22, 95% CI 0.98-1.52, p = 0.07). According to subgroup analysis, we also did not find a significant association between the hOGG1 Ser326Cys polymorphism and BC risk in Asians and Caucasians considered separately. Conclusions: The current meta-analysis suggests that the hOGG1 Ser326Cys polymorphism is not significantly associated with BC risk.