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Hydroxypropyl-?-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs.

ABSTRACT: The objective of the present study was to demonstrate that a novel hydroxypropyl-?-cyclodextrin functionalized calcium carbonate (HP-?-CD/CC) based amorphous solid dispersion (ASD) can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a model compound and loaded into the nanoporous HP-?-CD/CC matrix using an immersion method. The IRB-loaded HP-?-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM), dynamic light scattering (DLS), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-?-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-?-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-?-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (C max) and the area under the mean plasma concentration-time curve (AUC[0?48]) of IRB-loaded HP-?-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-?-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly demonstrate that HP-?-CD/CC based porous ASD is a promising formulation approach to improve the aqueous solubility and the in vivo absorption performance of a water-insoluble compound like IRB.

SUBMITTER: Zhang L

PROVIDER: S-EPMC4425320 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Hydroxypropyl-β-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs.

Zhang Lihua L Zhu Wufu W Lin Qisi Q Han Jin J Jiang Liqun L Zhang Yanzhuo Y

International journal of nanomedicine 20150430

The objective of the present study was to demonstrate that a novel hydroxypropyl-β-cyclodextrin functionalized calcium carbonate (HP-β-CD/CC) based amorphous solid dispersion (ASD) can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a model compound and loaded into the nanoporous HP-β-CD/CC matrix using an immersion method. The IRB-loaded HP-β-CD/CC formulation was characterized by various analytical techniques, such as speci ...[more]

PMID: 25995635

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Project description:Androst-4-ene-3,17-dione (AD) and androst-1,4-diene-3,17-dione (ADD) are valuable steroid pharmaceutical intermediates obtained by soybean phytosterol biotransformation by Mycobacterium Cyclodextrins (CDs) are generally believed to be carriers for phytosterol delivery and can improve the production of AD and ADD due to their effects on steroid solubilization and alteration in cell wall permeability for steroids. To better understand the mechanisms of CD promotion, we performed proteomic quantification of the effects of hydroxypropyl-β-CD (HP-β-CD) on phytosterol metabolism in Mycobacterium neoaurum TCCC 11978 C2. Perturbations are observed in steroid catabolism and glucose metabolism by adding HP-β-CD in a phytosterol bioconversion system. AD and ADD, as metabolic products of phytosterol, are toxic to cells, with inhibited cell growth and biocatalytic activity. Treatment of mycobacteria with HP-β-CD relieves the inhibitory effect of AD(D) on the electron transfer chain and cell growth. These results demonstrate the positive relationship between HP-β-CD and phytosterol metabolism and give insight into the complex functions of CDs as mediators of the regulation of sterol metabolism.IMPORTANCE Phytosterols from soybean are low-cost by-products of soybean oil production and, owing to their good bioavailability in mycobacteria, are preferred as the substrates for steroid drug production via biotransformation by Mycobacterium However, the low level of production of steroid hormone drugs due to the low aqueous solubility (below 0.1 mmol/liter) of phytosterols limits the commercial use of sterol-transformed strains. To improve the bioconversion of steroids, cyclodextrins (CDs) are generally used as an effective carrier for the delivery of hydrophobic steroids to the bacterium. CDs improve the biotransformation of steroids due to their effects on steroid solubilization and alterations in cell wall permeability for steroids. However, studies have rarely reported the effects of CDs on cell metabolic pathways related to sterols. In this study, the effects of hydroxypropyl-β-CD (HP-β-CD) on the expression of enzymes related to steroid catabolic pathways in Mycobacterium neoaurum were systematically investigated. These findings will improve our understanding of the complex functions of CDs in the regulation of sterol metabolism and guide the application of CDs to sterol production.

Dataset Information

Hydroxypropyl-?-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs.

Publications

Hydroxypropyl-β-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs.

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