Construction And Representation Of Nanopaticle Based On Carnitine Transporter

Objective:Drug’s adverse pharmacokinetic properties themselves result in them not being administered orally.Nanotechnology can improve the solubility and stability of drugs.In addition,targeted drug delivery systems can further enrich drugs at the target site,and the combination of both can sharply improve the oral bioavailability of drugs,thus enabling oral drug delivery.In this study,carnitine and palmitic acid were used as raw materials to synthesize PC,which,being specifically recognized and absorbed by intestinal OCTN2,could be inserted into PLGA nanoparticles.Meanwhile,the introduction of nanotechnology of PLGA improves the solubility and slows the release of drugs,further improving the oral bioavailability of drugs.Methods:Using carnitine and palmitic acid as raw materials,palmitoyl carnitine was synthesized,and ~1H-NMR and MS was used to verify it.Using HP-β-CD as inclusion material,CUR-CD was prepared by freeze-drying with cosolvent.The encapsulation efficiency and drug loading of curcumin inclusion complex were determined by ultraviolet spectrophotometry.The inclusion compounds were evaluated by differential scanning calorimetry and X-ray diffraction.Using PLGA as carrier material,curcumin or its clathrate compound was packaged to prepare nanoparticles,and then palmitoyl carnitine was introduced to prepare PLGA nanoparticles modified with different proportions of palmitoyl carnitine.The drug loading and encapsulation efficiency of PLGA nanoparticles were evaluated by ultraviolet spectrophotometry.The physical and chemical characteristics of PLGA nanoparticles were measured by TEM and dynamic light scattering.XPS was used to test whether PC was successfully loaded in the surface of PLGA nanoparticles.The release of PLGA nanoparticles was evaluated by dialysis in vitro.Results:The project successfully synthesized palmitoyl carnitine,screened out a simple and easy preparation route with relatively high yield,and confirmed the chemical structure of the synthesized OCTN2 substrate by ~1H-NMR and MS.The inclusion compound was prepared using curcumin as model drug and HP-β-CD as inclusion material.To the CUR-CD,the average encapsulation rate was 78.65%±1.1%and the average drug loading was 5.80%±0.08%.PC-CUR-PLGA NPs and PC-CUR-CD-PLGA NPs were prepared with PC as modifier.The results of dynamic light scatterometer and TEM showed that the particle sizes of the two preparations were 110～140 nm and the zeta potential was-2.62～0.0997.To PC-CUR-PLGA NPs,the maximum drug loading was 11.70%±0.22%,and the encapsulation rate was 88.76%±3.2%.To PC-CUR-CD-PLGA NPs,its maximum drug loading was only 0.35%±0.03%.The drug loading capacity of PC-CUR-CD-PLGA NPs preparations was low,but the drug loading capacity and encapsulation rate of PC-CUR-PLGA NPs preparations were better,so the latter was selected for follow-up experiments.In vitro release results showed that the release of naked curcumin reached 100%at 72 h,while the release of PLGA nanoparticle was only60%,and the release of PLGA nanoparticle was only 70%at 168 h.Conclusions:1.The ligand of OCTN2 was successfully prepared.2.The curcumin inclusion was successfully prepared and characterized,which proved that the inclusion action improved the solubility of curcumin.3.PC was successfully inserted onto the surface of PLGA nanoparticles,and it was proved that PLGA nanoparticles can prolong the release time of curcumin.