A smart O2-generating nanocarrier optimizes drug transportation comprehensively for chemotherapy improving

@#Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.

Leukocytoclastic Vasulitis Induced by Methoxy Polyethylene Glycol-Epoetin Beta / 대한피부과학회지

Methoxy polyethylene glycol-epoetin beta (Mircera(R), Roche), a third-generation erythropoiesis-stimulating agent (ESA) is known as a continuous erythropoietin receptor activator (CERA). In patients with anemia associated with chronic kidney disease (CKD), it is administered intravenously or subcutaneously. Treatment-related adverse events induced by methoxy polyethylene glycol-epoetin beta occurred in 6%. Hypertension, diarrhea and nasopharyngitis were the most commonly reported adverse events. Cutaneous adverse reactions are rarely experienced with methoxy polyethylene glycol-epoetin beta including maculopapular eruption, facial erythema, and tinea pedis. To the best of our knowledge, no cases of leukocytoclastic vasculitis associated with methoxy polyethylene glycol-epoetin beta have ever been published in medical literature. Herein, we report on a case of leukocytoclastic vasulitis induced by methoxy polyethylene glycol-epoetin beta in a patient with anemia associated with chronic kidney disease.

The study of MePEG content and chain density on MePEG-PLGA-NP surface with 1H-NMR method / 中国药学杂志

OBJECTIVE: 1H-NMR (Nuclear Magnetic Resonance Method) was used to quantitatively determine the MePEG (me-thoxy polyethylene glycol) content and chain density on MePEG-PLGA-NP surface, and study the influences of MePEG molecular weights and proportion on the chemical and physical properties of MePEG-PLGA-NP surface. METHODS: MePEG-PLGA-NP were prepared by self-emulsion solvent diffusion method with methoxy polyethylene glycol-poly(lactic acid-hydroxyl acid) copolymer (Me-PEG-PLGA) as the carriers. And the particle average size and Zeta potential were characterized. 1H-NMR method were used to ascertain the composition of the MePEG-PLGA copolymer and determine the MePEG content and chain density on the MePEG-PLGA-NP surface, and compared with colorimetric assay. RESULTS: The composition of MePEG-PLGA copolymer are basically the same with the labelled amount. When the Molecular weight is at the same, along with the increase of proportion of MePEG, the average size of MePEG-PLGA-NP decrease, the absolute value of the Zeta potential also decrease gradually, MePEG content on particles surface (α) increase gradually, the MePEG chain density on nanoparticles surface (δ) increase gradually, the distance between two adjacent MePEG chains on the surface of the particles (D) decrease; When there is the same proportions, with MePEG chain length increases, nanoparticles are not significantly different on the particle average size and the Zeta potential, whereas α increase gradually, the δ decreases, and D increases; Theavalue of the same MePEG-PLGA-NP determined by colorimetric assay is higher than which is determined by 1H-NMR. CONCLUSION: 1H-NMR method can be used to quantitatively determine the MePEG content and chain density on MePEG-PLGA-NP surface; Compared with the traditional method, the results determined by 1H-NMR method are more accurate. With the experimental limits, MePEG molecular weighs and proportion have influences on the chemical and physical properties of MePEG-PLGA NP surface, such as mean size, Zeta potential and the MePEG content and chain density on nanoparticles surface. Copyright 2012 by the Chinese Pharmaceutical Association.

Chemical Modification of RBC Surface Antigen with Methoxy Polyethylene Glycol / 대한임상병리학회지

BACKGROUND: Today, blood group antigens are a strong barrier of safe transfusion. We evaluated the change of agglutinability of antibody to RBC surface antigen before and after activated methoxy polyethylene glycol (mPEG) modification. METHODS: We collected blood from healthy volunteers and the blood were treated by activated mPEG (MW 5,000, Sigma, USA). Agglutinability of RBC was measured using anti-sera (Green Cross, Korea) in ABO and Rh(D) groups, and compared the agglutinability changes before and after mPEG treatment. RESULTS: The agglutinability of Rh(D) surface antigen (n=20) was disappeared after mPEG treatment. However, ABO antigens showed variable agglutinability against antisera, some of which showed no change at all. CONCLUSIONS: In the case of Rh(D) antigen, it would be useful to apply mPEG treated RBCs for clinical use, if the safety problem were solved. But in the case of ABO antigen, the more evaluation of the condition of reaction and the concentration of mPEG should be needed.

Chemical camouflage of like human B antigens on Rhesus monkey red blood cells with methoxy polyethylene glycol / 中国输血杂志

Objective To observe the chemical camouflage effects of methoxy polyethylene glycol(mPEG) on like human B antigens on Rhesus monkey red blood cell(rRBC) and to study the safety of transfusion with mPEG modified monkey RBC(mPEG rRBC).Methods rRBC were modified with 3mg/ml mPEG. The rRBC blood group and the effects of mPEG modification on blood conversion were assayed by absorption and elution methods.The structural and functional changes of mPEG rRBC were also tested.The survival fraction of mPEG modified like B rRBC in like A recipient monkey were examined by flow cytometry.The transfusion effects of mPEG modified rRBC on recipient's blood and urine were also observed.Results mPEG have been covalently bound to the surface of Rhesus monkey RBC (like human B blood group),mPEG could cover rRBC like B antigen.Transfusion of mPEG modified like B rRBC to like A Rhesus monkey had no harmful effects on the recipient.Conclusion The present study suggests that transfusion of mPEG modified RBC could be safety in experimental animals