| Vitamin A(VA)and Vitamin E(VE)are two fat-soluble vitamins with many biological functions.However,both vitamin A and vitamin E have problems such as low solubility,easy oxidation,and low bioavailability,which greatly limits their application in biological functions.Hydroxypropyl ?-cyclodextrin(HP-?-CD)is widely used for encapsulation of drugs and increasing the solubility of poorly soluble drugs.Modification of hydroxypropyl cyclodextrin can provide cyclodextrin with pH and temperature Sensitive and other characteristics.In response to the above problems,a pH-sensitive ?-cyclodextrin derivative has been prepared in this subject,and a series of studies have been carried out using vitamin A and E as model drugs:(1)Preparation and evaluation(2)Evaluation of solubilizing effect of ?-cyclodextrin derivatives(3)Evaluation of drug-loading properties of ?-cyclodextrin derivatives inclusion compounds(4)pH-sensitive properties of ?-cyclodextrin derivatives Evaluation.It mainly includes the following:(1)Using ethylene diamine(EN)and urea(Urea)two cross-linking agents,it was prepared by oxidizing sodium hydroxypropyl ?-cyclodextrin(HP-?-CD)with sodium periodate.Two ?-cyclodextrin derivatives.UV spectrophotometry was established to determine the content of vitamin A and vitamin E,respectively.The optimal crosslinking ratio of cross-linking agent to HP-?-CD in two ?-cyclodextrin derivatives was screened out by saturation solubility experiments.The binding strength and recombination efficiency of vitamin A and vitamin E with two cross-linked ?-cyclodextrin derivatives were determined through phase solubility studies.According to the experimental measurement,the solubility of vitamin E is most obviously improved when the ratio of ethylene-diamine cross-linked ?-cyclodextrin derivative(EN-HP-?-CD)to ethylene diamine is 1: 1.When the concentration of EN-HP-?-CD is 1.5 mg / mL,the solubility of vitamin E can be increased by 25 times.The urea-crosslinked ?-cyclodextrin derivative(Urea-HP-?-CD)to urea ratio of 3:1 has the most significant improvement in the solubility of vitamin A.When Urea-HP-?-CD concentration is 1.5 mg / mL,the solubility of vitamin A can be increased by 32 times.(2)Preparation of VE-EN-complex and VE-Urea-complex of drug-loaded vitamin A inclusion complex and vitamin E inclusion compound cross-linked by two kinds of cross-linking agents,and determination of the encapsulation rate and drug loading of the inclusion compound A preliminary evaluation of the inclusion complex was performed,and the ?-cyclodextrin derivatives and the ?-cyclodextrin derivatives were prepared using Fourier transform infrared spectroscopy(FT-IR),differential scanning calorimetry(DSC),and X-ray diffraction(XRD).The inclusion complex was characterized,and the morphology of the inclusion complex was observed by scanning electron microscopy(SEM).The results showed that for the drug vitamin A,the encapsulation rate of 3:1 Urea-HP-?-CD was the highest,which was 66.88 ± 4.56%,and the drug loading was 15.38 ± 1.12%;for the drug vitamin E,1:1 EN The encapsulation rate of HP-?-CD was 51.50 ± 3.77%,and the drug loading was 15.45 ± 1.03%.Structural characterization results show that HP-?-CD successfully cross-linked ?-cyclodextrin derivatives with a C = N bond under the action of a cross-linking agent,and the synthetic derivatives can successfully contain the fat-soluble drugs vitamin A and vitamin E.(3)The in vitro release behavior of vitamin A and vitamin E inclusion complexes at different pH values was investigated.In vitro release experiments measured the cumulative release of vitamin A,vitamin E and their inclusion compounds in phosphate buffers at pH 4.5 and pH 7.0 within 24 h.The results of vitamin A release showed that the cumulative release of 3:1Urea-HP-?-CD was the highest at 24 hours,reaching 95.91% at pH 4.5 and 66.68% at pH 7.0.The cumulative release rate of uncrosslinked HP-?-CD in 24 h was 58.84%.The results of vitamin E release showed that the cumulative release of 1:1 EN-HP-?-CD was the highest in 24 hours,reaching 78.22% at pH 4.5 and 43.77% at pH 7.0.Less than 1%,the cumulative release rate of uncrosslinked HP-?-CD within 24 h was 22.83%.The release behavior experiment results show that the prepared cyclodextrin derivatives have a certain pH sensitivity. |
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