摘要：It is crucial to maintaining the viability of biofabricated human-sized tissues to ensure their successful survival and function after *** is a purine nucleoside that has the function to suppress cellular metabolism and has been previously proposed as a method to prolong cell viability under *** this study,we optimized the dose concentration of adenosine for incorporation into bioprinted constructs to preserve long-term cell viability in *** results showed that muscle cells(C2C12)containing 6,7,or 8 mM adenosine maintained high cell viability for 20 days under hypoxic conditions(0.1%O2),whereas cells without adenosine treatment showed 100%cell death after 11 *** 20 days under hypoxic conditions,muscle cells treated with adenosine proliferated and differentiated when transferred to normoxic *** these adenosine concentrations,6 mM was picked as the optimized adenosine concentration for further investigations due to its most effective results on improving cell *** bioprinted muscle constructs containing adenosine(6 mM)maintained high cell viability for 11 days under hypoxic conditions,while the control constructs without adenosine had no live *** in vivo validation,the bioprinted constructs with adenosine implanted under the dorsal subcutaneous space in mice,showed the enhanced formation of muscle tissue with minimal central necrosis and apoptosis,when compared to the constructs without *** positive in vitro and in vivo results demonstrate that the use of adenosine is an effective approach to preventing the challenge of hypoxia-induced necrosis in bioprinted tissues for clinical translation.

摘要：The aim of this study was to design and evaluate extended-release formulations of a model drug,nicorandil,in order to achieve the desired steady-state plasma concentration of drug in *** was employed to estimate optimum dissolution and absorption rate of *** dissolution test was employed using pH 1.2,4.0,6.8 buffer solution,or water,to measure the in vitro release behaviors of nicorandil formulations.A single dose(15 mg)of each formulation was orally administered to four beagle dogs under fasted conditions,and the pharmacokinetic parameters were *** in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle *** was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release *** nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release *** release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extendedrelease *** results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.