Poly(ethylene glycol)-Conjugation and Deoxygenation Enable Long-Term Preservation of Hemoglobin-Vesicles as Oxygen Carriers in a Liquid State

2000 ◽  
Vol 11 (3) ◽  
pp. 425-432 ◽  
Author(s):  
Hiromi Sakai ◽  
Ken-ichi Tomiyama ◽  
Keitaro Sou ◽  
Shinji Takeoka ◽  
Eishun Tsuchida
Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 605
Author(s):  
Marie-Emérentienne Cagnon ◽  
Silvio Curia ◽  
Juliette Serindoux ◽  
Jean-Manuel Cros ◽  
Feifei Ng ◽  
...  

This article describes the utilization of (methoxy)poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) ((m)PEG–PTMC) diblock and triblock copolymers for the formulation of in situ forming depot long-acting injectables by solvent exchange. The results shown in this manuscript demonstrate that it is possible to achieve long-term drug deliveries from suspension formulations prepared with these copolymers, with release durations up to several months in vitro. The utilization of copolymers with different PEG and PTMC molecular weights affords to modulate the release profile and duration. A pharmacokinetic study in rats with meloxicam confirmed the feasibility of achieving at least 28 days of sustained delivery by using this technology while showing good local tolerability in the subcutaneous environment. The characterization of the depots at the end of the in vivo study suggests that the rapid phase exchange upon administration and the surface erosion of the resulting depots are driving the delivery kinetics from suspension formulations. Due to the widely accepted utilization of meloxicam as an analgesic drug for animal care, the results shown in this article are of special interest for the development of veterinary products aiming at a very long-term sustained delivery of this therapeutic molecule.


2015 ◽  
Vol 15 (12) ◽  
pp. 1679-1686 ◽  
Author(s):  
Xinming Tong ◽  
Soah Lee ◽  
Layla Bararpour ◽  
Fan Yang

2018 ◽  
Vol Volume 13 ◽  
pp. 2743-2754 ◽  
Author(s):  
Jianwei Duan ◽  
Chao Liu ◽  
Xiaoyu Liang ◽  
Xuanling Li ◽  
Youlu Chen ◽  
...  

2006 ◽  
Vol 399 (3) ◽  
pp. 463-471 ◽  
Author(s):  
Kim D. Vandegriff ◽  
Ashok Malavalli ◽  
Charles Minn ◽  
Eva Jiang ◽  
Jeff Lohman ◽  
...  

Haemoglobin-based oxygen carriers can undergo oxidation of ferrous haemoglobin into a non-functional ferric form with enhanced rates of haem loss. A recently developed human haemoglobin conjugated to maleimide-activated poly(ethylene glycol), termed MP4, has unique physicochemical properties (increased molecular radius, high oxygen affinity and low cooperativity) and lacks the typical hypertensive response observed with most cell-free haemoglobin solutions. The rate of in vitro MP4 autoxidation is higher compared with the rate for unmodified SFHb (stroma-free haemoglobin), both at room temperature (20–22 °C) and at 37 °C (P<0.001). This appears to be attributable to residual catalase activity in SFHb but not MP4. In contrast, MP4 and SFHb showed the same susceptibility to oxidation by reactive oxygen species generated by a xanthine–xanthine oxidase system. Once fully oxidized to methaemoglobin, the rate of in vitro haem loss was five times higher in MP4 compared with SFHb in the fast phase, which we assign to the β subunits, whereas the slow phase (i.e. haem loss from α chains) showed similar rates for the two haemoglobins. Formation of MP4 methaemoglobin in vivo following transfusion in rats and humans was slower than predicted by its first-order in vitro autoxidation rate, and there was no appreciable accumulation of MP4 methaemoglobin in plasma before disappearing from the circulation. These results show that MP4 oxidation and haem loss characteristics observed in vitro provide information regarding the effect of poly(ethylene glycol) conjugation on the stability of the haemoglobin molecule, but do not correspond to the oxidation behaviour of MP4 in vivo.


2012 ◽  
Vol 46 (12) ◽  
pp. 3737-3753 ◽  
Author(s):  
Daniel J. Miller ◽  
Paula A. Araújo ◽  
Patricia B. Correia ◽  
Matthew M. Ramsey ◽  
Joop C. Kruithof ◽  
...  

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