Preparation And Assessment Of Tilmicosin-Loaded Nanostructured Lipid Carriers

Tilmicosin(TLM)is a macrolide antibiotic synthesied from tylosin through chemical modification,and with properties that include broad antifungal spectrum,low inhibitory concentrations and a large distribution volume.It is widely used in the veterinary medicine for the treatment of bacterial respiratory diseases and mammary infections in swine and cattle,et al.But because of poor water solubility and bitter in taste,the development of TLM was been limited.Nowadays,TLM is available in subcutaneous injection and premix caused different treatment effects.To improve the aqueous solubility and bioavailability TLM,TLM-loaded nanostructured lipid carriers(TLM-NLCs)was prepared and tested.1 Preparation and characteristics of tilmicosin-loaded nanostructured lipid carriers using high shearing-ultrasonicationFirstly,screening an optimized formulation of TLM-NLCs,then high shearing and ultrasonication was performed to prepare uniform,milky TLM-NLCs suspension(HU-TLM-NLCs).After that,TLM-NLCs were characterized by measurements of average particle size,polydispersity index,zeta potential,morphology,thermal analysis,crystallization,stability,drug entrapment efficiency and drug loading.These results showed that the optimized HU-TLM-NLCs was nearly spherical in shape with a mean diameter of 376.9±14.6 nm,PDI of 0.234±0.034,and zeta potential of around 20.5 mV.Entrapment efficiency(EE)of TLM-NLCs was above 89%,drug loading(DL)was about 9%.Furthermore,it was confirmed that TLM-NLCs has formed a new physical phase,according to the results of IR,DSC and XRD.The stability studies showed that it is better to place TLM-NLCs at 4 ? for long-term storage.These characteristics remained unchanged after TLM-NLCs diluted in pH 2.0,but degradation happened after diluted in pH 7.0.All these evidences indicated that TLM-NLCs was successfully prepared.2 Pharmacokinetics of TLM-NLCs prepared by high pressure homogenization methodThe optimal formula was applied to high pressure homogenization method to realize mass production of TLM-NLCs preparation(HH-TLM-NLCs).And particle size,polydispersity index,zeta potential,morphology was investigated in same ways mentioned before.Then,HH-TLM-NLCs and TLM crude drug were administered to swines orally to determine the concentration of drug in blood plasma and its kinetic behavior.The plasma samples were analyzed by the HPLC method established in this study,and statistics on pharmacokinetics were dealt with data processing software.After compared pharmacokinetic parameters of TLM-NLCs and TLM crude drug,it is easy to find the absorption,distribution and excretion TLM-NLCs was slower,whereas the mean residence time(MRT)of TLM-NLCs was longer than crude drug.The area under concentration-time curve(AUC)of TLM-NLCs was approximately 1.42-fold greater than TLM crude drug.These results indicated TLM-NLCs could control and sustain the release of drug,and could improve the oral absorption and the bioavailability of TLM.In general,the NLCs mentioned in this study has high drug entrapment efficiency and could be well prepared by high pressure homogenization method.NLCs are a potential delivery system for oral administration of TLM.