Inclusion complex of colchicine in hydroxypropyl-β-cyclodextrin tenders better solubility and improved pharmacokinetics

Chauhan, Ritu; Madan, Jitender; Kaushik, Dinesh; Sardana, Satish; Pandey, Ravi Shankar; Sharma, Rakesh Kumar

doi:10.3109/10837450.2011.591801

Cited by 22 publications

(8 citation statements)

References 12 publications

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“…HPMC and HPβCD degradation curves were analogous, as expected due to their similar chemical structure. The curves showed only one degradation step, as consequence of compounds decomposition . Hydrogels TGA profiles were alike, with just one degradation step.…”

Section: Resultsmentioning

confidence: 89%

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Smart Hydrogel for the pH‐Selective Drug Delivery of Antimicrobial Compounds

Pinho

Machado

Soares

2019

Macromolecular Symposia

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Infection is a major prompt of chronic wounds, increasing the pH on the injury tissues. Thus, pH can be used as trigger for antimicrobial agents’ delivery, preventing chronic wounds. Hence, the present work aimed to develop a hydrogel with drug delivery capacity, modulated by environmental pH. Chitosan was used as electrolyte monomer and it was crosslinked with hydroxypropyl methylcellulose and 2‐hydroxypropyl‐β‐cyclodextrin. The polymeric network assembly was confirmed by FTIR and thermal analysis. The developed hydrogels behaved as superabsorbent systems, with higher swelling at pH 7. Caffeic acid loading was ruled by the inclusion complex formation between the phenolic acid and cyclodextrin. Chitosan hydrogels delivery capacity was pH‐dependent and, also, more efficient at pH 7. Based on the Peppas–Sahlin model, fickian diffusion was the main mechanism responsible for caffeic acid release. Based on the results, the developed hydrogel can be used to prevent wound infection, due to its ability to release antimicrobial agents when the wound pH rises.

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Section: Resultsmentioning

confidence: 89%

“…HPMC (black) and HPβCD (light blue) profiles showed large endothermic peak (65 and 80 °C), due to water evaporation. Moreover, HPMC profile exhibited two endothermic peaks (330 and 350 °C) and HPβCD just one (350 °C) as consequence of their thermal decomposition …”

Section: Resultsmentioning

confidence: 99%

Smart Hydrogel for the pH‐Selective Drug Delivery of Antimicrobial Compounds

Pinho

Machado

Soares

2019

Macromolecular Symposia

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“…Phase-solubility analysis has been carried out for colchicine binding to HP--CD, studying solubility as a function of cyclodextrin concentration over the range in phosphate buffered saline (pH 7.4) containing various concentrations of HP-β-CD (M w~1 600; 30-180 mM) based on the maximum solubility of HP-β-CD (50% w/v at 25°C) in water (Chauhan et al, 2013). Solubility was found to increase in a linear fashion, indicative of 1:1 binding classified as A L type according to nomenclature introduced by Higuchi and Connors (1965), and a binding constant, K, of 310 M -1 reported (Chauhan et al, 2013). Assuming no change to K when colchicine is the end group in the structure of Fig.…”

Section: Ict01-2588 Binding To Hp--cdmentioning

confidence: 99%

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

Zaman

Bright

Adams

et al. 2017

International Journal of Pharmaceutics

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There is a need to understand the nature of aggregation of cyclodextrins (CDs) with guest molecules in increasingly complex formulation systems. To this end an innovative application of Taylor dispersion analysis (TDA) and comparison with dynamic light scattering (DLS) have been carried out to probe the nature of ICT01-2588 (ICT-2588), a novel tumor-targeted vascular disrupting agent, in solvents including a potential buffered formulation containing 10% hydroxypropyl-betacyclodextrin. The two hydrodynamic sizing techniques give measurement responses are that fundamentally different for aggregated solutions containing the target molecule, and the benefits of using TDA in conjunction with DLS are that systems are characterised through measurement of both mass-and z-average hydrodynamic radii. Whereas DLS measurements primarily resolve the large aggregates of ICT01-2588 in its formulation medium, methodology for TDA is described to determine the size and notably to quantify the proportion of monomers in the presence of large aggregates, and at the same time measure the formulation viscosity. Interestingly TDA and DLS have also distinguished between aggregate profiles formed using HP-beta-CD samples from different suppliers. The approach is expected to be widely applicable to this important class of drug formulations where drug solubility is enhanced by cyclodextrin and other excipients. To: The Editor, International Journal of Pharmaceutics From: Rob Forbes and David GoodallWe have revised the manuscript to reflect the amendments of the reviewers. The original cover letter is below.We are submitting this article, which describes novel work showing benefits of use of Taylor dispersion analysis in conjunction with dynamic light scattering to characterize ICT01-2588, a tumour-targeted vascular disrupting agent, in a potential formulation medium containing 10% hydroxypropyl--cyclodextrin as a solubility enhancing agent. Our approach is expected to be widely applicable to this important class of drug formulations where drug solubility is enhanced by cyclodextrin and other excipients, and is a contribution to advancing an understanding of the nature of self-assembly in such complex systems.The lead reviwer suggested is Thorsteinn Loftsson, who is a member of your Editorial Advisory Board. We cite a number of his papers. Of the other suggested referees. We cite work on Taylor dispersion analysis by the other two proposed referees, Ana Ribeiro and Jesper Ostergaard, and Robert HoylstPlease note that if possible we would like to name two corresponding authors, Robert T. Forbes (lead corresponding author) and David M. Goodall (second corresponding author). If this is not possible, it should be just Robert T. Forbes. The bulk of this work was conducted whilst Professor Forbes was at the University of Bradford, which is listed as his affiliation #1. He is currently at the University of Central Lancashire, which is listed as affiliation #2.Regarding declaration of conflict of interest guidelines, please note the foll...

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“…Lactobionic acid (4-O-b-galactopyranosyl-D-gluconic acid) yields gluconic acid and galactose on oxidation of lactose and acts as a template for the fabrication of galactosylated nanocarriers [11]. We reported that polymeric nanovesicles and microvesicles are the promising drug delivery systems for intracellular delivery of proteins and drugs [12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Galactosylated gelatin nanovectors of doxorubicin inhibit cell proliferation and induce apoptosis in hepatocarcinoma cells

et al. 2012

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We have synthesized and characterized doxorubicin (DOX)-loaded galactosylated gelatin nanovectors using in vitro and in vivo for targeting liver cells including hepatocarcinoma cells. Galactosylated and nongalactosylated gelatin nanovectors (GL-GN-DOX and GN-DOX) were spherical in shape and had mean sizes of about 95.1 and 88.3 nm, respectively. In-vitro release of DOX from nanovectors followed first-order kinetics and was pH dependent. Galactosylated formulation released 95.2% of DOX compared with 86.6% by nongalactosylated formulation at pH 5.8. However, the release rate was suppressed at pH 7.4. Further, we showed that GL-GN-DOX had greater growth inhibitory effect on HepG2 in terms of low inhibitory concentration (IC(50); 0.35 µg/ml) compared with GN-DOX (0.75 µg/ml) and induced caspase-3-mediated apoptosis in HepG2 cells. This might be due to efficient internalization of galactosylated nanovectors by HepG2 cells compared with unmodified formulation. Pharmacokinetic and biodistribution analyses show that galactosylated formulation deposits 24.5 µg/g of DOX in targeted tissue (liver) in comparison with heart (0.3 µg/g) at a single dose of 10 mg/kg. These results suggest that DOX-loaded galactosylated gelatin nanovectors warrant future in-depth antitumor study to scale-up technology and may be used for the management of hepatocarcinoma.

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Inclusion complex of colchicine in hydroxypropyl-β-cyclodextrin tenders better solubility and improved pharmacokinetics

Abstract: CLC-HP-β-CD inclusion complex may potentially be used as a viable formulation of CLC.

Cited by 22 publications

References 12 publications

Smart Hydrogel for the pH‐Selective Drug Delivery of Antimicrobial Compounds

Smart Hydrogel for the pH‐Selective Drug Delivery of Antimicrobial Compounds

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

Galactosylated gelatin nanovectors of doxorubicin inhibit cell proliferation and induce apoptosis in hepatocarcinoma cells

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