Skin compatibility of cyclodextrins and their derivatives: a comparative assessment using a corneoxenometry bioassay

Schönfelder

J Biomedical Materials Res

et al. 2007

Safety and efficacy of pharmaceutical agents can be greatly improved by encapsulation within, or covalent attachment to, a biomaterial carrier. Drug delivery systems must deliver the necessary amount of drug to the targeted site for a necessary period of time, both efficiently and precisely. Various kinds of high-performance biomaterials are being constantly developed for this purpose. Cyclodextrins are potential candidates for such a role, because of their ability to alter physical, chemical, and biological properties of guest molecules through the formation of inclusion complexes. The alpha-, beta-, and gamma-cyclodextrins are widely used natural cyclodextrins, consisting of six, seven, and eight D-glucopyranose residues, respectively, linked by -1,4 glycosidic bonds into a macro cycle. Each cyclodextrin has its own ability to form inclusion complexes with specific guests, an ability, which depends on a proper fit of the guest molecule into the hydrophobic cyclodextrin cavity. The most common pharmaceutical application of cyclodextrins is to enhance the solubility, stability, and bioavailability of drug molecules. Such kinds of ligand-receptor complexes can be used for different applications, e.g., for a transdermal therapeutic system (TTS) or in biofunctional textiles. The aim of this study was the investigation of the influence of the different cyclodextrins on the cell proliferation using HaCaT keratinocytes as an in vitro test system. Moreover, the study was performed to find harmless and nontoxic cyclodextrin concentrations for dermal applications. By means of different independent in vitro tests could be confirmed that alpha-, beta-, and gamma-cyclodextrins in concentrations up to 0.1% (w/v) do not show any antiproliferative influence on HaCaT keratinocytes. Sometimes even proliferative effects could be found. However, all used cyclodextrins (besides gamma-cyclodextrin and its derivatives) in concentrations of 0.5 and 1% (w/v), respectively, exert a cytotoxic influence on the proliferation of HaCaT keratinocytes. On the basis of these findings, the following rank order of cyclodextrins regarding their cytotoxicity was proposed: M-beta-CD > beta-CD > HP-beta-CD > alpha-CD > (gamma-CD). It could be confirmed that beta-CD and M-beta-CD trigger the activity of the effectors caspases -3 and -7. A significant increase of LDH release could be found for beta-CD and methyl-beta-CD in concentrations of 0.5 and 1% (w/v). The calculated cytotoxicity amounted 45 and 79%, respectively. The measurements of the interleukins IL-6 and IL-8 confirmed the findings of the proliferation assays as well as the LDH measurements. These findings may provide further rationale to the use of CDs in topical formulations for dermal and transdermal drug delivery or as raw material to functionalize textiles for medical applications.

Section: Discussionmentioning

confidence: 99%

Influence of cyclodextrins on the proliferation of HaCaT keratinocytes in vitro

Schönfelder

J Biomedical Materials Res

et al. 2007

“…[146] Skin compatibility with CDs, both natural and a wide range of derivatives, has been reported by other researchers. [147] In general, all types of CDs can be used in skin and mucosal formulations safely and without risk of irritation; even methylated CDs in low concentrations can be safely applied. Only for aqueous solution/suspension containing high concentration of CDs there is some possibility that methylated CD will interact with the stratum corneum lipids (cholesterol and triglycerides) and temporarily affect the membrane integrity.…”

Section: Cyclodextrin In Topical Drug Deliverymentioning

confidence: 99%

Untitled

Budhwar¹

2018

AJP

Inclusion complexes have various applications in different fields of drug delivery and pharmaceutical industry due to their ability of complexation with guest molecules and enhancement of the physicochemical properties of guest molecules. Cyclodextrins and their derivatives have the ability to encapsulate the bioactive compounds into its cavity and protect these from the environmental conditions, improve the solubility, bioavailability, and other properties also. The aim of this review is to highlight the advantages of cyclodextrins in the enhancement of physicochemical properties of drugs (such as solubility, stability, bioavailability, permeability, and others), different methods for production and various characterization techniques used for evaluation of complexes. Applications of cyclodextrin complexes in pharmaceutical and other fields are also explained here with examples. Thus cyclodextrins, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems accompanied with the delivery of different novel drugs through various delivery routes.

J Incl Phenom Macrocycl Chem

“…Several studies showed that cholesterol-containing membranes are more sensitive to methylated CD than to natural CD [16,19,20]. Among the former, the randomly methylated β-CD (RAMEB) passed all toxicological tests [16,[19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Small-Angle Neutron Scattering investigation of cholesterol-doped DMPC liposomes interacting with β-cyclodextrin

Joset

Grammenos

Hoebeke

et al. 2015

The Small Angle Neutron Scattering technique (SANS) has been applied to investigate the interaction between a cyclodextrin (CD) and liposomes. From the modelling of the experimental neutron scattering cross sections, the detailed structure of dimyristoylphosphatidylcholine (DMPC) liposomes is assessed upon addition of increasing amounts of randomly methylated β-CD (RAMEB). This study has been performed at two temperatures bracketing the phase transition of the DMPC bilayers. The fraction of DMPC molecules incorporated into the vesicles is inferred. The dose-dependent phospholipidic extraction by RAMEB is quantified as well as the concomitant evolution of the liposome radius and of the thickness of the hydrophobic and hydrophilic parts of the membrane. The possible formation of CD-DMPC inclusion complexes is also assessed. The data suggest the dose-dependent coverage by RAMEB of the outer liposome interface. Our analysis highlights the important role of temperature on the mechanism of action of RAMEB. These results are discussed in the framework of the Area-Difference-Elasticity model.