Optimization of the formulation of IMP-RH60/mPEG-PLLA micelles by central composite design-response surface methodology and its evaluation in vitro
Objective:To optimize the preparation process of imperatorin micelles loaded with Cremophor® RH 60/monomethoxy poly(ethylene glycol)-block-poly(L-lactide)(IMP-RH60/mPEG-PLLA)by central composite design-response surface methodology.Methods:On the basis of single factor investigation,the dosage of RH60,the ratio of drug and carrier and the water volume were taken as independent variables,the entrapment rate and loading capacity were determined as dependent variables.Central composite design-response surface methodology was used to carry out three factors and three levels experiment,and the results were analyzed to get the optimal prescription process.The micelles release was evaluated by in vitro release behavior and cellular uptake.Results:The optimal prescription of IMP-RH60/mPEG-PLLA micelles was determined as follows:the dosage of RH60 was 28 mg,the dosage of IMP was 1.2 mg,the dosage of mPEG-PLLA was 10 mg,and the water volume was 6 mL.The IMP-RH60/mPEG-PLLA micelles prepared under these conditions had an average particle size of(25.48±0.92)nm,Zeta potential of-(5.50±1.06)mV,entrapment rate of(85.78±0.84)％,and the loading capacity of IMP was(2.66±0.03)％.The in vitro release test showed that the release of IMP from IMP-RH60/mPEG-PLLA micelles was significantly better than that of IMP API,and the results of cellular uptake test indicated that IMP-RH60/mPEG-PLLA micelles could promote the uptake of IMP.Conclusion:The mathematic model established by central composite design-response surface methodology has high accuracy and could be used to optimize the formulation of IMP-RH60/mPEG-PLLA micelles preparations.
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