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Turabee, Md Hasan,Jeong, Tae Ho,Ramalingam, Prakash,Kang, Ji Hee,Ko, Young Tag Elsevier 2019 Carbohydrate polymers Vol.203 No.-
<P><B>Abstract</B></P> <P>The malignant gliomas are most destructive brain tumor having low drug response. The thermosensitive hydrogel from pluronic F127 (PF127) and <I>N</I>,<I>N</I>,<I>N</I>-trimethyl chitosan (TMC) is developed as a drug delivery system for anticancer drug docetaxel (DTX) to the glioblastoma multiforme. The influence of TMC on morphology, physico-chemical, mechanical, and release properties of PF127 based thermosensitive hydrogel is investigated here. The hydrogels shows porous network as shown by scanning electron microscopy and TMC addition hindered close packing of PF127 layers in the gel system leaving more pores on the surface. TEM images demonstrate micelle formation by PF127-TMC with diameters of about 50 nm. MTT assay result shows that DTX loaded PF127-TMC hydrogel is more capable of killing U87MG cell than free DTX and DTX loaded PF-127. Hydrogels retain sustained release of DTX under different pH conditions more than one month. Furthermore, in vivo experiments are carried out by creating xenograft tumor model on the head of BALB/c nude mice for checking tumor suppression by PF127-TMC/DTX hydrogel. Overall, the hydrogels shows sustained release of DTX on different pH with tumor suppression suggests that it can be used for treating tumor.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Thermosensitive Pluronic F127 hydrogel embedded with N,N,N-trimethyl chitosan. </LI> <LI> Temperature sensitive sol-gel transition at physiological condition. </LI> <LI> Hydrogel with sustained release of anticancer drug docetaxel over significant amount of time. </LI> </UL> </P>
Turabee, Md. Hasan,Thambi, Thavasyappan,Duong, Huu Thuy Trang,Jeong, Ji Hoon,Lee, Doo Sung The Royal Society of Chemistry 2018 Biomaterials Science Vol.6 No.3
<P>Sustained delivery of protein therapeutics is limited owing to the fragile nature of proteins. Despite its great potential, delivery of proteins without any loss of bioactivity remains a challenge in the use of protein therapeutics in the clinic. To surmount this shortcoming, we report a pH- and temperature-responsive <I>in situ</I>-forming injectable hydrogel based on comb-type polypeptide block copolymers for the controlled delivery of proteins. Polypeptide block copolymers, composed of hydrophilic polyethylene glycol (PEG), temperature-responsive poly(γ-benzyl-l-glutamate) (PBLG), and pH-responsive oligo(sulfamethazine) (OSM), exhibit pH- and temperature-induced sol-to-gel transition behavior in aqueous solutions. Polypeptide block copolymers were synthesized by combining <I>N</I>-carboxyanhydride-based ring-opening polymerization and post-functionalization of the chain-end using <I>N</I>-hydroxy succinimide ester activated OSM. The physical properties of polypeptide-based hydrogels were tuned by varying the composition of temperature- and pH-responsive PBLG and OSM in block copolymers. Polypeptide block copolymers were non-toxic to human embryonic kidney cells at high concentrations (2000 μg mL<SUP>−1</SUP>). Subcutaneous administration of polypeptide block copolymer sols formed viscoelastic gel instantly at the back of Sprague-Dawley (SD) rats. The <I>in vivo</I> gels exhibited sustained degradation and were found to be bioresorbable in 6 weeks without any noticeable inflammation at the injection site. Anionic characteristics of hydrogels allow efficient loading of a cationic model protein, lysozyme, through electrostatic interaction. Lysozyme-loaded polypeptide block copolymer sols readily formed a viscoelastic gel <I>in vivo</I> and sustained lysozyme release for at least a week. Overall, the results demonstrate an elegant approach to control the release of certain charged proteins and open a myriad of therapeutic possibilities in protein therapeutics.</P>
Giang Phan, V.H.,Duong, Huu Thuy Trang,Thambi, Thavasyappan,Nguyen, Thanh Loc,Turabee, Md. Hasan,Yin, Yue,Kim, Seong Han,Kim, Jaeyun,Jeong, Ji Hoon,Lee, Doo Sung IPC Science and Technology Press 2019 Biomaterials Vol.195 No.-
<P><B>Abstract</B></P> <P>Lymphoid organs, which are populated by dendritic cells (DCs), are highly specialized tissues and provide an ideal microenvironment for T-cell priming. However, intramuscular or subcutaneous delivery of vaccine to DCs, a subset of antigen-presenting cells, has failed to stimulate optimal immune response for effective vaccination and need for adjuvants to induce immune response. To address this issue, we developed an in situ-forming injectable hybrid hydrogel that spontaneously assemble into microporous network upon subcutaneous administration, which provide a cellular niche to host immune cells, including DCs. In situ-forming injectable hybrid hydrogelators, composed of protein-polymer conjugates, formed a hydrogel depot at the close proximity to the dermis, resulting in a rapid migration of immune cells to the hydrogel boundary and infiltration to the microporous network. The biocompatibility of the watery microporous network allows recruitment of DCs without a DC enhancement factor, which was significantly higher than that of traditional hydrogel releasing chemoattractants, granulocyte-macrophage colony-stimulating factor. Owing to the sustained degradation of microporous hydrogel network, DNA vaccine release can be sustained, and the recruitment of DCs and their homing to lymph node can be modulated. Furthermore, immunization of a vaccine encoding amyloid-β fusion proteinbearing microporous network induced a robust antigen-specific immune response in vivo and strong recall immune response was exhibited due to immunogenic memory. These hybrid hydrogels can be administered in a minimally invasive manner using hypodermic needle, bypassing the need for cytokine or DC enhancement factor and provide niche to host immune cells. These findings highlight the potential of hybrid hydrogels that may serve as a simple, yet multifunctional, platform for DNA vaccine delivery to modulate immune response.</P>