Heparin-based temperature-sensitive injectable hydrogels for protein delivery

2015 ◽  
Vol 3 (45) ◽  
pp. 8892-8901 ◽  
Author(s):  
Hye Jin Sim ◽  
Thavasyappan Thambi ◽  
Doo Sung Lee

Polysaccharide-based biodegradable, biocompatible and temperature-sensitive injectable hydrogels have been developed for the sustained delivery of proteins.

2019 ◽  
Vol 304 (9) ◽  
pp. 1900279 ◽  
Author(s):  
Seong Han Kim ◽  
Thavasyappan Thambi ◽  
Jae Seung Lym ◽  
V.H. Giang Phan ◽  
Doo Sung Lee

Nanoscale ◽  
2015 ◽  
Vol 7 (7) ◽  
pp. 3043-3054 ◽  
Author(s):  
Narendra K. Singh ◽  
Quang Vinh Nguyen ◽  
Bong Sup Kim ◽  
Doo Sung Lee

The combination of layered double hydroxide nanoclay particles and pH/temperature-sensitive hydrogel matrix effectively controlled the delivery of human growth hormone.


2010 ◽  
Vol 160-162 ◽  
pp. 1072-1076 ◽  
Author(s):  
Ju Yang ◽  
Dan Qun Huo ◽  
Chang Jun Hou ◽  
Guo Ping Zhang ◽  
Li Min Yang ◽  
...  

A novel protein delivery system with incorporating PLGA microspheres into porous PNIPAAm hydrogel for sustained delivery of proteins was successfully developed. Distribution of PLGA microspheres in the hydrogel was determined by SEM, and the in vitro protein release characteristics of combination system were investigated by UV-vis spectroscopy. The SEM results showed that PLGA microspheres were encased into the interconnected porous structure of PNIPAAm hydrogel. In vitro release of BSA from combination system exhibited a less burst release followed by a slower sustained release for 20 days. The slow release after the initial burst release was due to the low permeability of BSA in PLGA microspheres. The controlled release of BSA encapsulated within microspheres embedded in scaffolds was better controlled when compared to delivery from PNIPAAm hydrogels alone. The combination systems showed great promise for application in protein delivery.


2018 ◽  
Vol 54 (5A) ◽  
pp. 142
Author(s):  
Dai Phu Huynh

For recent decades, researchers have been increasing their attention to pH/temperature-sensitive polymers as drug/protein delivery systems. In this research, we aim to synthesize a new pH/temperature sensitive pentablock based on D,L-Serine. Amino groups of D,L-Serine were modified with benzenesulfonyl chloride in order to create sulfonamide groups as desired pH-sensitive groups. Pentablocks were then synthesized by conjugation reaction between carboxylic, hydroxyl groups of D,L-Serine and hydroxyl-terminal groups of temperature sensitive triblock PCL-PEG-PCL. The synthesized products were analyzed by 1H-NMR and their molecular weights were measured by gel permeation chromatography (GPC). The sol-gel transition of pentablock was also investigated by the inverting test method. The pH dependent property of the pH sensitive moiety could be very useful for preparing drug carriers.


2020 ◽  
Author(s):  
Lucia Massi ◽  
Adrian Najer ◽  
Robert Chapman ◽  
Christopher Spicer ◽  
Valeria Nele ◽  
...  

<p>Many diseases are associated with the dysregulated activity of enzymes, such as matrix metalloproteinases (MMPs). This dysregulation can be leveraged in drug delivery to achieve disease- or site-specific cargo release. Self-assembled polymeric nanoparticles are versatile drug carrier materials due to the accessible diversity of polymer chemistry. However, efficient loading of sensitive cargo, such as proteins, and introducing functional enzyme-responsive behaviour remain challenging. Herein, peptide-crosslinked, temperature-sensitive nanogels for protein delivery were designed to respond to MMP-7, which is overexpressed in many pathologies including cancer and inflammatory diseases. The incorporation of <i>N-</i>cyclopropylacrylamide (NCPAM) into <i>N</i>-isopropylacrylamide (NIPAM)-based copolymers enabled us to tune the polymer lower critical solution temperature from 33 to 44 °C, allowing the encapsulation of protein cargo and nanogel-crosslinking at slightly elevated temperatures. This approach resulted in nanogels that were held together by MMP-sensitive peptides for enzyme-specific protein delivery. We employed a combination of cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small angle neutron scattering (SANS), and fluorescence correlation spectroscopy (FCS) to precisely decipher the morphology, self-assembly mechanism, enzyme-responsiveness, and model protein loading/release properties of our nanogel platform. Simple variation of the peptide linker sequence and combining multiple different crosslinkers will enable us to adjust our platform to target specific diseases in the future.</p>


2017 ◽  
Vol 33 (2) ◽  
pp. 224-236 ◽  
Author(s):  
Bahar Demirdirek ◽  
Kathryn E Uhrich

Physically crosslinked hydrogels were developed via solvent casting methods using a temperature-sensitive polymer, poly( N-isopropylacrylamide- co-acrylic acid), and a therapeutic polymer, salicylate-based poly(anhydride-esters), to concurrently release salicylic acid and bovine serum albumin in a sustained manner. The physical interactions between the two polymer systems were confirmed using Fourier transform infrared spectroscopy. The crosslinked polymers were porous, thus able to encapsulate bovine serum albumin (23 wt%) and then released the protein in a sustained fashion over 96 h. Concurrently, the hydrogel releases salicylic acid in a sustained manner up to 120 h. Hydrogel systems were cytocompatible at relevant therapeutic concentrations. These hydrogel systems can be used for simultaneous delivery of salicylic acid and protein to achieve synergic effects.


Nanoscale ◽  
2018 ◽  
Vol 10 (42) ◽  
pp. 20020-20032 ◽  
Author(s):  
Jiangshan Wan ◽  
Shinan Geng ◽  
Hao Zhao ◽  
Xiaole Peng ◽  
Jiabao Xu ◽  
...  

Temperature sensitive polymers were modified onto gold nanocages, and the resultant temperature sensitive hydrogels achieved precise synchronization of hyperthermia and chemotherapy by the on-demand release.


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