Preparation Of HA-PDM Composite Colloidal Particles And Drug Research Performance

[Objective] The HA is a kind of linear linear anionic polysaccharide, it has excellent biocompatibility, moisturizing, unique viscoelastic and good water-solubility. HA is widely used in clinic, cosmetics and the development of drug formulation. But it is sensitive to acid, alkali, heat, free radicals and hyaluronidase, prone to degradation, thus limits its application. In This experiment will use HA and hydrophobic monomer to prepare self-assembled, loratadine and domperidone as the model drug, and investigate the release behavior of the drugs in the acidic environment. The experiment will provide a new kind of drug carrier that easy-degradated in acidic condition.[Methods] The HA as polyanion electrolyte, dimethylaminoethyl acrylate methyl(DM) as cationic hydrophobic monomer, formed hydrophobic monomer by electrostatic assembly body with HA, prepares a parent colloid particles by emulsion polymerization of DM. The experiment Filter the preparation prescription of HA-PDM composite colloidal particles by using orthogonal analysis method. Using zeta potential meter, TEM, particle size measuring instrument and FT-IR to analysis the drug carrier, preparing drug-load of loratadine and domperidone by the method of solvent evaporation and using uv to determine drug-loading rate and the in vitro release rate.[Results] The optimal preparation prescription of the HA-PDM carrier is the initiator is APS:FeSo4=4:1, HA:DM:the initiator 1.5:1:0.5, the solution concentration of the HA is 3 mg/ml, the HA-DM mixed solution PH is 4.52, reaction temperature is 60 ℃, the reaction time is 5 h, the PH of dialysis solution is 5, from HA, We can know from FT-IR map of PDM, HA-PDM and HA, the absorption peak 1730 cm-1 and 1737 cm-1 in the PDM and HA owe to the-C=O of the carbonyl group, but in the FT-IR map of HA-PDM, intensity of this absorption peak becomes weak, and the peak moves to 1670 cm-1. So we judge this situation may due to the formation of the ionic bond between carboxyl in HA and protonated tertiary amine of PDM, however, the absorption peak is not obvious, in the process of preparation, the Zeta potential is in-30～40 range, as the experiment carried out, the absolute value of zeta reduce, compare with the zeta potential of HA and PDM, the zeta of composite colloidal particle between the HA and PDM, and particle size of the composite colloidal particles decreases as the reaction proceeded, due to the electrostatic interaction between HA and PDM, form self-assembled polymer colloidal particles. The best prescription of domperidone drug loading is:the carrier: domperidone=1:1, reaction time is 2 h, reaction temperature is 75 ℃, drug-loading rate is 17.61%, the release rate of domperidone in the cumulative simulated acid environment is 117.30%. the accumulative release rate of domperidone HA-PDM polymer colloidal particles in a simulated gastric acid environment is 67.78%. The optimal preparation of loratadine prescription is:the carrier:loratadine=1:3, the reaction time is 25 min, reaction temperature is 60 ℃, drug-loading rate is 20.4%, the cumulative release rate of loratadine in the simulated acid environment is 92. 68%. Loratadine HA-PDM polymer colloidal particles in a simulated gastric acid environment is 79.67%.[conclusion] According to Zeta potential and particle size and FT-IR map, it shows that the HA-PDM carrier as a composite colloidal particles is formed by electrostatic reaction, through this two drugs in vitro release can be seen that under the condition of acid, HA-PDM colloidal particle has certain protective effect on the drug.