scholarly journals Pre-existing anti-polyethylene glycol antibody reduces the therapeutic efficacy and pharmacokinetics of PEGylated liposomes

Theranostics ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 3164-3175 ◽  
Author(s):  
Yuan-Chin Hsieh ◽  
Hsin-Ell Wang ◽  
Wen-Wei Lin ◽  
Steve R. Roffler ◽  
Ta-Chun Cheng ◽  
...  
2021 ◽  
Author(s):  
Vedagopuram Sreekanth ◽  
Sanjay Pal ◽  
Sandeep Kumar ◽  
Varsha Komalla ◽  
Poonam Yadav ◽  
...  

Herein, we present the engineering of a supramolecular nanomicellar system that is composed of self-assembled units of PEGylated lithocholic acid (LCA)-Docetaxel (DTX) conjugate (LCA-DTX-PEG). We tethered a short polyethylene glycol...


2001 ◽  
Vol 45 (5) ◽  
pp. 1487-1492 ◽  
Author(s):  
Irma A. J. M. Bakker-Woudenberg ◽  
Marian T. ten Kate ◽  
Luke Guo ◽  
Peter Working ◽  
Johan W. Mouton

ABSTRACT Animal and clinical data show that high ratios of the area under the concentration-time curve and the peak concentration in blood to the MIC of fluoroquinolones for a given pathogen are associated with a favorable outcome. The present study investigated whether improvement of the therapeutic potential of ciprofloxacin could be achieved by encapsulation in polyethylene glycol (PEG)-coated long-circulating sustained-release liposomes. In a rat model of unilateralKlebsiella pneumoniae pneumonia (MIC = 0.1 μg/ml), antibiotic was administered at 12- or 24-h intervals at twofold-increasing doses. A treatment period of 3 days was started 24 h after inoculation of the left lung, when the bacterial count had increased 1,000-fold and some rats had positive blood cultures. The infection was fatal within 5 days in untreated rats. Administration of ciprofloxacin in the liposomal form resulted in delayed ciprofloxacin clearance and increased and prolonged ciprofloxacin concentrations in blood and tissues. The ED50 (dosage that results in 50% survival) of liposomal ciprofloxacin was 3.3 mg/kg of body weight/day given once daily, and that of free ciprofloxacin was 18.9 mg/kg/day once daily or 5.1 mg/kg/day twice daily. The ED90 of liposomal ciprofloxacin was 15.0 mg/kg/day once daily compared with 36.0 mg/kg/day twice daily for free ciprofloxacin; 90% survival could not be achieved with free ciprofloxacin given once daily. In summary, the therapeutic efficacy of liposomal ciprofloxacin was superior to that of ciprofloxacin in the free form. PEG-coated liposomal ciprofloxacin was well tolerated in relatively high doses, permitting once daily administration with relatively low ciprofloxacin clearance and without compromising therapeutic efficacy.


2020 ◽  
Vol 12 (2) ◽  
pp. 271-277
Author(s):  
Eman R. Abbase ◽  
Medhat W. Shafaa ◽  
Mohsen M. Mady

In order to improve liposomal doxorubicin stability, differentiation between Heparin and Polyethylene Glycol (PEG) as biofunctionalization for liposomal doxorubicin has been investigated by measuring the entrapment efficiency, size distribution, zeta potential, evaluating the in vitro potential cytotoxicity against MCF-7 (Breast cancer cell) and stability in serum by measuring the drug release rate. We synthesized Four liposomal formulations: (A) Conventional liposomes; DPPC:DOX, (B) Positively charged PEGylated liposomes; DPPC:CHOL:SA:PEG:DOX (C) Negatively charged PEGylated liposomes: DPPC:CHOl:DCP:PEG:DOX (D) positively charged liposomes to conjugate heparin; DPPC:CHOL:SA:DOX. Entrapment efficiency of doxorubicin dramatically increased after PEGylation and conjugation with heparin. In addition, zeta potential was changed upon the encapsulation of doxorubicin into conventional and PEGylated liposomes which indicates that DOX encapsulated completely into liposomes. For heparin conjugated liposomes, zeta potential was slightly changed. Sulphorhodamine-B (SRB) assay showed a greater cytotoxic effect of the liposomal doxorubicin formulations at different concentrations with respect to free drug against MCF-7 cell lines. The anticancer activity order was observed between the various liposome formulations, especially those observed with conjugated heparin liposomes. Slower drug release rate showed an order of D > C > B > A that means stability showed an order of D > C > B > A. From above results, the most stable liposomal doxorubicin formulation was the liposomal formulation D. The results optimized using heparin than PEG as biofunctionalization. Further studies are suggested for better understanding why heparin improves the stability of liposomal doxorubicin.


2015 ◽  
Vol 136 ◽  
pp. 885-891 ◽  
Author(s):  
Ehsan Marzban ◽  
Seyedeh Hoda Alavizadeh ◽  
Maral Ghiadi ◽  
Mostafa Khoshangosht ◽  
Zahra Khashayarmanesh ◽  
...  

RSC Advances ◽  
2016 ◽  
Vol 6 (44) ◽  
pp. 37740-37749 ◽  
Author(s):  
Daizheng Lian ◽  
Yuhan Chen ◽  
Gang Xu ◽  
Xiaowei Zeng ◽  
Zhuangling Li ◽  
...  

Nanoformulation of siRNA targeting HIF-1α loaded chitosan modified TPGS-b-(PCL-ran-PGA) NPs could increase the therapeutic potential of cisplatin for nasopharyngeal carcinoma.


2012 ◽  
Vol 160 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Alberto Gabizon ◽  
Yasmine Amitay ◽  
Dina Tzemach ◽  
Jenny Gorin ◽  
Hilary Shmeeda ◽  
...  

2021 ◽  
Author(s):  
Anna Adler ◽  
Yuuki Inoue ◽  
Yuya Sato ◽  
Kazuhiko Ishihara ◽  
Kristina N Ekdahl ◽  
...  

Polyethylene glycol (PEG) is frequently used for liposome surface modification. However, as PEGylated liposomes are cleared rapidly from circulation upon repeated injections, substitutes of PEG are being sought. We focused...


2021 ◽  
Vol 22 (17) ◽  
pp. 9226
Author(s):  
Lidia Gómez-Cid ◽  
María Luisa López-Donaire ◽  
Diego Velasco ◽  
Víctor Marín ◽  
María Isabel González ◽  
...  

Stem-cell-derived extracellular vesicles (EVs) have demonstrated multiple beneficial effects in preclinical models of cardiac diseases. However, poor retention at the target site may limit their therapeutic efficacy. Cardiac extracellular matrix hydrogels (cECMH) seem promising as drug-delivery materials and could improve the retention of EVs, but may be limited by their long gelation time and soft mechanical properties. Our objective was to develop and characterize an optimized product combining cECMH, polyethylene glycol (PEG), and EVs (EVs–PEG–cECMH) in an attempt to overcome their individual limitations: long gelation time of the cECMH and poor retention of the EVs. The new combined product presented improved physicochemical properties (60% reduction in half gelation time, p < 0.001, and threefold increase in storage modulus, p < 0.01, vs. cECMH alone), while preserving injectability and biodegradability. It also maintained in vitro bioactivity of its individual components (55% reduction in cellular senescence vs. serum-free medium, p < 0.001, similar to EVs and cECMH alone) and increased on-site retention in vivo (fourfold increase vs. EVs alone, p < 0.05). In conclusion, the combination of EVs–PEG–cECMH is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy.


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