Studies On The Enhancement For Solubility And Therapeutic Effect Of Hydrophobic Drugs

According to statistics,about 40%of the drug molecules in drug research process are hydrophobic drugs.Duing to its low solubility in water,the drugs are difficult to be absorbed by the body,resulting the low bioavailability;Besides,hydrophobic drugs aggregates easily in aqueous solution,brings new security issues,further restricting the application and reducing the therapeutic effects.Therefore,increasing the solubility and improving the therapeutic effect of hydrophobic drugs have to be settled urgently.This paper mainly focuses on two kinds of hydrophobic drugs docetaxel and IR780,increasing the solubility and improving the therapeutic effect.The main research contents are as follows:(1)Using our patent technology,we selected albumin as the drug carrier to entrapped hydrophobic drug docetaxel(DTX)and prepared DTX-loaded albumin nano-formulation.It displayed good solubiliy,high stability in suspension,which can significantly increase the solubility of docetaxel(over 1000 folds).By establising the analysis method of docetaxel related substances,the stability of nano-formulations were studied.Including the affecting factors,accelerated and long-term experimental study,we found the content of 7-epi-docetaxel increased rapidly;then we further focused on studying its properties.The growth of related substances may affect the therapeutic effect of drug.Combined with its own characteristics,we studied the relationships between residual moisture,residual ethanol,lyoprotectant and 7-epi docetaxel content.The residual amount of ethanol and 7-epi docetaxel content showed positive correlation.By optimizaing the freeze-drying curve,removal of residual ethanol.Meanwhile,screening out the 5%glucose was the most optimal cryoprotectant for nanoformulation.By controling the 7-epi docetaxel content,the effectiveness of drug treatment can be ensured.Finally,we evaluated the 7-epi docetaxel toxicity of docetaxel and antitumor effect of different 7-epi content formulations in vitro and in vivo.7-epi docetaxel proved lower anti-tumor effect,further confirmed the necessity to control 7-epi docetaxel content.By albumin solubilization technology and controlling the 7-epi docetaxel content,improving solubility of docetaxel and ensuring the quality stability of nano-formulation to achieve therapeutic effect.(2)In this study,we selected IR780 as the representative drug and firstly modified the structure of IR780 by adding the PEG2000 to the one side of IR780 molecule and the C13 carbon chain to the other side to form a new material PEG-IR780-C13 to improve its solubility.In our previous work,the material showed good stability,solubility and good phototherapeutic effect.Next,hydrophobic drugs docetaxel(DTX)was entrapped into the PEG-IR780-C13 to form a drug carrier,DTX@PEG-IR780-C13.After the screening of preparation process,the DTX@PEG-IR780-C13 drug carrier can be improved solubility combined with photothermal therapy,showed more effective treatment at the cellular level which enhances the therapeutic effect of a single treatment.Finally,the PFTBA(a type of PFC)was selected and encapsulated into PEG-IR780-C13 to form PFTBA@PEG-IR780-C 13(a photodynamic therapy enchancer).We investigated the photodynamic effect of PFTBA@PEG-IR780-C13 by evaluating 1O2 generation ability in vitro.The photodynamic cancer treatment effectiveness was explored both in vivo and in vitro,respectively.We used this new approach to achieve the encouraging PDT therapeutic outcomes of IR780 dyes.