scholarly journals Modulating the Thermoresponse of Polymer-Protein Conjugates with Hydrogels for Controlled Release

Polymers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 2772
Author(s):  
Vincent Huynh ◽  
Natalie Ifraimov ◽  
Ryan G. Wylie

Sustained release is being explored to increase plasma and tissue residence times of polymer-protein therapeutics for improved efficacy. Recently, poly(oligo(ethylene glycol) methyl ether methacrylate) (PEGMA) polymers have been established as potential PEG alternatives to further decrease immunogenicity and introduce responsive or sieving properties. We developed a drug delivery system that locally depresses the lower critical solution temperature (LCST) of PEGMA-protein conjugates within zwitterionic hydrogels for controlled release. Inside the hydrogel the conjugates partially aggregate through PEGMA-PEGMA chain interactions to limit their release rates, whereas conjugates outside of the hydrogel are completely solubilized. Release can therefore be tuned by altering hydrogel components and the PEGMA’s temperature sensitivity without the need for traditional controlled release mechanisms such as particle encapsulation or affinity interactions. Combining local LCST depression technology and degradable zwitterionic hydrogels, complete release of the conjugate was achieved over 13 days.

NANO ◽  
2020 ◽  
Vol 15 (03) ◽  
pp. 2050040 ◽  
Author(s):  
Jia Liu ◽  
Juan Li ◽  
Tingting Liu

In this report, mixed polymeric micelles (MPMs) system self-assembled from two kinds of cholesterol-grafted amphiphilic block copolymers cholesterol modified poly ([Formula: see text]-amino esters)-grafted disulfide poly (ethylene glycol) methyl ether (PAE(-ss-mPEG)-[Formula: see text]-Chol) and poly([Formula: see text]-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-[Formula: see text]-mPEG-Chol) were prepared for drug delivery and controlled release with pH and redox-responsibilities. The self-assembly of two block copolymers was evaluated by measurement of critical micelle concentration (CMC) values using fluorescence spectroscopy. The hydrodynamic diameter, polydispersity index (PDI) and zeta-potential of MPMs in aqueous were recorded by dynamic light scattering (DLS) at different conditions. Doxorubicin (DOX) was efficiently encapsulated in the micellar core by the hydrophobic interaction. The drug loading content (LC) and encapsulation efficacy (EE) of MPMs with different formulations were evaluated. The DOX was released due to the swelling and disassembly of MPMs induced by low pH and high glutathione (GSH) concentrations. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values and reducing agents. The results showed that the MPMs could be the potential anticancer drug delivery carriers with pH/redox-triggered drug release profile.


2014 ◽  
Vol 5 (8) ◽  
pp. 3061-3070 ◽  
Author(s):  
Yohei Kotsuchibashi ◽  
Ravin Narain

Dual-temperature and pH responsive (ethylene glycol)-based nanogels were synthesized. Both the core and the shell of the nanogels showed a lower critical solution temperature (LCST) and the LCST of the shell was strongly affected by the solution pH and salt concentration due to the presence of carboxylic acid groups at the nanogel surface.


2003 ◽  
Vol 14 (2) ◽  
pp. 395-403 ◽  
Author(s):  
Richard B. Greenwald ◽  
Karen Yang ◽  
Hong Zhao ◽  
Charles D. Conover ◽  
Stanford Lee ◽  
...  

2020 ◽  
Vol 2 (10) ◽  
pp. 4498-4509
Author(s):  
Majed Alghamdi ◽  
Filippo Chierchini ◽  
Dimitri Eigel ◽  
Christian Taplan ◽  
Thomas Miles ◽  
...  

Soft and flexible poly(ethylene glycol)-based nanotubes load doxorubicin for controlled release to glioblastoma multiforme.


2006 ◽  
Vol 18 (05) ◽  
pp. 222-228 ◽  
Author(s):  
CHUN-TE TAO ◽  
TAI-HORNG YOUNG

Poly N-isopropylacrylamide (PNIPAAm) is a well-known temperature-sensitive polymer. When the temperature is higher than the lower critical solution temperature (LCST), PNIPAAm aquous solution is cloudy (phase separation occurred). In contrast, when the temperature is lower than the LCST, PNIPAAm is soluble in water (a homogeneous solution). The lower critical solution temperature (LCST) in aqueous solution of PNIPAAm was about 32~33°C. We prepared nano-scaled PNIPAAm particles containing carboxylic group on their surfaces by introducing acrylic acid monomer. The carboxylic groups were applied to conjugate with the amino group of the CD34 antibody. This immuno-conjugate can be applied on targeting the human CD34 positive cells, peripheral blood progenitor cells included, for cell purification and drug controlled release. In order to the active responding of controlled release of the conjugate in the body influenced by temperature, we hope to estimate the shifting of the gel-collapse temperature or cloud point of the immuno-conjugates by dynamic light scattering (DLS) and UV absorption. The results show that the gel-collapse temperature of the nano-particle was not significantly affected by the content of AA between 1.5~5 mol%. However, cloud point of the solution was elevated by the conjugation of CD34 antibody to 37°C. When CD34-conjugated particle was subsequently incorporated with recombinant FLT3-ligand, which is a smaller molecule compare to CD34 antibody, cloud point of the solution was not affected.


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