Preparation and Characterization of Targeted Drug Carrier Materials Poly-β-Cyclodextrin-PEG-Folate Acid
Issue:
Volume 9, Issue 2, June 2023
Pages:
16-22
Received:
8 June 2023
Accepted:
3 July 2023
Published:
11 July 2023
Abstract: Objective: Targeted drug delivery can concentrate drugs at the lesion site and selectively kill lesion cells. Folate receptors have limited expression in human healthy cells but are over-expressing on the surface of cancer cells. Our study decided to develop one of site-specific intracellular delivery against the folate receptor. Methods: First, poly β-CD-PEG-OCH3 and poly β-CD-PEG-FA were synthesized according to respective reaction routes and were confirmed by 1H nuclear magnetic resonance (1H NMR) and infrared spectroscopy (IR). Second, busulfan was selected as drug model and loaded into the carriers by self-assembly. The cytotoxicity of poly-β-CD-PEG-OCH3, busulfan loaded poly-β-CD-PEG-OCH3, poly-β-CD-PEG-FA and busulfan loaded poly-β-CD-PEG-FA was determined by a crystal violet stain assay. Last, The potential of poly-β-CD-PEG-FA for use in the targeting delivery of busulfan was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis in HepG2, which contain folate receptors on its surfaces. Results: poly β-CD-PEG-OCH3 and poly β-CD-PEG-FA were successfully synthesized and proved by 1H NMR and IR. Busulfan was successfully loaded into poly β-CD-PEG-FA and poly β-CD-PEG-OCH3 and their content are 3.379 mg/g and 3.548 mg/g, respectively. Poly β-CD-PEG-OCH3 and poly β-CD-PEG-FA with the concentration between 12.5-50 μg/ml had no effect on cell survival rate of HepG2 cells but with over 100 μg/ml had a significant inhibitory effect. The MTT results revealed that in HepG2 cells, the cytotoxicity of poly-β-CD-PEG-FA loaded busulfan cells is greater than that of poly-β-CD-PEG-OCH3 loaded busulfan. Conclusion: Poly-β-CD-PEG-FA can be used as a carrier for hydrophobic anticancer chemotherapeutic drugs. After being loaded into poly-β-CD-PEG-FA, busulfan still maintained its original anticancer activity and had obvious targeted drug delivery effect on tumor cells with folate receptor over-expression.
Abstract: Objective: Targeted drug delivery can concentrate drugs at the lesion site and selectively kill lesion cells. Folate receptors have limited expression in human healthy cells but are over-expressing on the surface of cancer cells. Our study decided to develop one of site-specific intracellular delivery against the folate receptor. Methods: First, po...
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Estimated Thermodynamic Parameters of Amlodipine by Group Contribution Method
Issue:
Volume 9, Issue 2, June 2023
Pages:
23-28
Received:
27 June 2023
Accepted:
13 July 2023
Published:
31 August 2023
Abstract: Objective: Amlodipine is the third-generation Calcium channel antagonist of dihydropyridine. which belongs to the first-line antihypertensive drug in clinic and used as racemate and levoisomer. The antihypertensive effection of levo-Amlodipine is twice as much as that of racemate. Physical property data of compounds are often used in scientific research, pharmaceutical process design, chemical and pharmaceutical production, synthesis and resolution of chiral drugs, etc., distinct and accurate estimation of physical property data will greatly save time and effort. In particular, thermodynamic parameters such as enthalpy, entropy and heat capacity are state functions, so in practical applications, a state of matter can be arbitrarily chosen as a reference state, and then calculated. In order to provide data support for the separation and industrial production of Amlodipine, the thermodynamic parameters of Amlodipine were estimated by Joback group contribution method which always used to estimated the thermodynamic parameters of industry product. The physical properties of Amlodipine, such as the melting boiling point, are generally related to the structure of matter. In this paper, by comparing the measurement of melting boiling point with the estimated value of group contribution method, it is shown that the group contribution method is reasonable to split the group, and the values of other thermodynamic properties estimated by the group contribution method have a certain degree of credibility, it can be used to calculate physical properties in industrial production. Method: The structure of Amlodipine was divided by Joback group contribution method, and the group contribution value was calculated to get the standard enthalpy of formation, Standard molar isobaric heat capacity, and residual entropy of Amlodipine. Result: the standard formation enthalpy of Amlodipine is -143.4KJ•mol-1, standard molar isobaric heat capacity of Amlodipine is108500J•K-1•mol-1, and residual entropy of Amlodipine is349.86J•K-1•mol-1. The melting temperature of Amlodipine was also estimated by Joback group contribution method at 1188.74 K, which was 230°C (503.15 K) measured by experiment and average relative error nearly4.05%. The boiling point temperature of Amlodipine was estimated by Joback method is 1005.97 K, which was 527.2°C (800.35 K) by measured. The average relative error ARD is 2.57%. Conclusion: The results show that the thermodynamic parameters of Amlodipine can be estimated by Joback group contribution method. Joback method has a high accuracy in estimating the boiling point of Amlodipine, and it quite fit with the melting point after revised.
Abstract: Objective: Amlodipine is the third-generation Calcium channel antagonist of dihydropyridine. which belongs to the first-line antihypertensive drug in clinic and used as racemate and levoisomer. The antihypertensive effection of levo-Amlodipine is twice as much as that of racemate. Physical property data of compounds are often used in scientific res...
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