Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, ...Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, hydrogel system was designed and expected to achieve a zero-order release Of biomolecular drugs in relativehigh initial drug loadings. Lysozyme, an antibacterial protein usually used to reduce prosthetic valve endocarditis,was selected as the model drug. Poly （DL-lactide-co-glycolide） （PLGA） microspheres, prepared by solvent evaporation method, were employee to encapsulate lysozyme and dispersed into thermosensitive pre-gel solution containing methylcellulose （MC）, polyethylene glycol （PEG）, sodium citrate （SC）, and sodium alginate （SA）. The mixture could act asadrug reservoir by.performing sol-gel transition rapidly if the temperature was raised from roomtemperature to 37℃. The in vitro release results showed that the burst effect was avoided due to strengthening ofdiffusion resistance in the gel. The formulation was able.to deliver lysozy.me for over.30 daysin a nearly zero-order release profile with a rate of 32.8μg.d^-1 which exhibits its remarkable potential for effective aoolication in long-term drug delivery.展开更多
Stem cell therapy is a promising approach to treat myocardial infarction. However, direct delivery of stem cells into hearts experiences poor cell engraftment and differentiation, due to ischemic conditions （low nutr...Stem cell therapy is a promising approach to treat myocardial infarction. However, direct delivery of stem cells into hearts experiences poor cell engraftment and differentiation, due to ischemic conditions （low nutrient and oxygen） in the infarct hearts. Development of suitable cell carriers capable of supporting cell survival and differentiation under these harsh conditions is critical for improving the efficacy of current stem cell therapy. In this work, we created a family of novel cell carriers based on thermosensitive hydrogels and insulin-like growth factor 1 （IGF-1）, and investigated if these cell carriers can improve cell sur- vival and differentiation under ischemic conditions. The thermosensitive hydrogels were synthesized from N-isopropylacryla- mide, acrylic acid, acrylic acid N-bydroxysuccinicimide ester, and 2-hydroxyethyl methacrylate-oligo（hydroxybutyrate）. The hydrogel solutions can be readily injected through 26G needles, and can quickly solidify at 37 ~C to form highly flexible hy- drogels. IGF-I was immobilized into the hydrogels in order to support long-term cell survival and differentiation. Different amount of IGF- 1 was immobilized by using hydrogels with different content of N-hydroxysuccinicimide ester groups. Cardio- sphere derived cells were encapsulated in the hydrogels and cultured under ischemic conditions. The results demonstrated that a significant improvement of cell survival and differentiation was achieved after IGF-1 immobilization. These IGF-1 immobi- lized hydrogels have the potential to improve cell survival and differentiation in infarct hearts.展开更多
基金Supported by the National Natural Science Foundation of China （No.20576057） and Fundamental Research Foundation of Tsinghua University （JCqn2005033）.
文摘Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, hydrogel system was designed and expected to achieve a zero-order release Of biomolecular drugs in relativehigh initial drug loadings. Lysozyme, an antibacterial protein usually used to reduce prosthetic valve endocarditis,was selected as the model drug. Poly （DL-lactide-co-glycolide） （PLGA） microspheres, prepared by solvent evaporation method, were employee to encapsulate lysozyme and dispersed into thermosensitive pre-gel solution containing methylcellulose （MC）, polyethylene glycol （PEG）, sodium citrate （SC）, and sodium alginate （SA）. The mixture could act asadrug reservoir by.performing sol-gel transition rapidly if the temperature was raised from roomtemperature to 37℃. The in vitro release results showed that the burst effect was avoided due to strengthening ofdiffusion resistance in the gel. The formulation was able.to deliver lysozy.me for over.30 daysin a nearly zero-order release profile with a rate of 32.8μg.d^-1 which exhibits its remarkable potential for effective aoolication in long-term drug delivery.
基金supported by the National Science Foundation of the United States(1160122,1006734)
文摘Stem cell therapy is a promising approach to treat myocardial infarction. However, direct delivery of stem cells into hearts experiences poor cell engraftment and differentiation, due to ischemic conditions （low nutrient and oxygen） in the infarct hearts. Development of suitable cell carriers capable of supporting cell survival and differentiation under these harsh conditions is critical for improving the efficacy of current stem cell therapy. In this work, we created a family of novel cell carriers based on thermosensitive hydrogels and insulin-like growth factor 1 （IGF-1）, and investigated if these cell carriers can improve cell sur- vival and differentiation under ischemic conditions. The thermosensitive hydrogels were synthesized from N-isopropylacryla- mide, acrylic acid, acrylic acid N-bydroxysuccinicimide ester, and 2-hydroxyethyl methacrylate-oligo（hydroxybutyrate）. The hydrogel solutions can be readily injected through 26G needles, and can quickly solidify at 37 ~C to form highly flexible hy- drogels. IGF-I was immobilized into the hydrogels in order to support long-term cell survival and differentiation. Different amount of IGF- 1 was immobilized by using hydrogels with different content of N-hydroxysuccinicimide ester groups. Cardio- sphere derived cells were encapsulated in the hydrogels and cultured under ischemic conditions. The results demonstrated that a significant improvement of cell survival and differentiation was achieved after IGF-1 immobilization. These IGF-1 immobi- lized hydrogels have the potential to improve cell survival and differentiation in infarct hearts.
