curcumin and calix(4)arene

In the search for soft and smart materials for nanomedicine, which is a present challenge, supramolecular nanohydrogels built on self-assembling low-molecular-weight building blocks attract interest for their structural, mechanical and functional properties. Herein, we describe a supramolecular nanohydrogel formed by a biofriendly micellar self-assembling choline-calix[4]arene derivative in the presence of curcumin, a natural and multitarget pharmacologically relevant drug. Morphology and mechanical properties of the nanohydrogel were investigated, and theoretical simulation performed to model the nanohydrogel structure. The self-healing and injectable nanohydrogel easily formed in PBS medium at physiologic pH, without using additives and organic solvents. The micellar nanohydrogel protected curcumin from rapid chemical and photochemical degradation, and slowly dissolved in curcumin-loaded micelles sustaining the drug release in a low rate. The nanohydrogel which combines the mechanical properties of a hydrogel and the benefits of a nanoscale micelle in drug delivery, appears a promising novel material for drug delivery.

Topics: Calixarenes; Computer Simulation; Curcumin; Drug Liberation; Drug Stability; Hydrogels; Injections; Micelles; Models, Molecular; Phenols; Rheology; Spectrophotometry, Ultraviolet; Viscosity

Curcumin (CUR) has shown remarkable efficacy in the treatment of skin diseases, but its effective transdermal delivery is still a major challenge and stimulates interest in the design of novel systems for CUR dispersion, preservation, and delivery facilitation to the deeper layers of the skin. The present work aimed to investigate the potential of a nanohydrogel, formed by a micellar choline-calix[4]arene amphiphile (CALIX) and CUR, in the treatment of skin diseases through an imiquimod (IMQ)-induced psoriasis model. Psoriasis plaques are associated with aberrant keratinization, abnormal distribution of tight junctions (TJs) proteins, and enhanced expression of inflammatory markers. The nanohydrogel restored the normal distribution of TJs proteins ZO1 and occludin and reduced the expression of TNF-α and inducible nitric oxide synthetase (iNOS) compared to the untreated IMQ group. The novelty lies in the calix[4]arene-based nanohydrogel as a potential new soft material for the topical skin delivery of CUR. The nanohydrogel, due to its physicochemical and mechanical properties, enhances the drug water-solubility, preserves CUR from rapid degradation, and eases the local skin administration and penetration.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calixarenes; Choline; Curcumin; Disease Models, Animal; Drug Carriers; Hydrogels; Male; Mice; Mice, Inbred BALB C; Phenols; Psoriasis

Curcumin is an Indian spice with a wide spectrum of biological and pharmacological activities but poor aqueous solubility, rapid degradation, and low bioavailability that affect medical benefits. To overcome these limits in ophthalmic application, curcumin was entrapped in a polycationic calix[4]arene-based nanoaggregate by a simple and reproducible method. The calix[4]arene-curcumin supramolecular assembly (Calix-Cur) appeared as a clear colloidal solution consisting in micellar nanoaggregates with size, polydispersity index, surface potential, and drug loading percentage meeting the requirements for an ocular drug delivery system. The encapsulation in the calix[4]arene nanoassembly markedly enhanced the solubility, reduced the degradation, and improved the anti-inflammatory effects of curcumin compared to free curcumin in both in vitro and in vivo experiments. Calix-Cur did not compromise the viability of J774A.1 macrophages and suppressed pro-inflammatory marker expression in J774A.1 macrophages subjected to LPS-induced oxidative stress. Histological and immunohistochemical analyses showed that Calix-Cur reduced signs of inflammation in a rat model of LPS-induced uveitis when topically administrated in the eyes. Overall, the results supported the calix[4]arene nanoassembly as a promising nanocarrier for delivering curcumin to anterior ocular tissues.

Topics: Animals; Calixarenes; Cell Line; Curcumin; Drug Carriers; Inflammation; Macrophages; Ophthalmic Solutions; Phenols; Uveitis

Gels are interesting soft materials owing to their functional properties leading to potential applications. This paper deals with the synthesis of monocholesteryl derivatized calix[4]arene (G) and its instantaneous gelation at a minimum gelator concentration of 0.6% in 1:1 v/v THF/acetonitrile. The gel shows remarkable thermoreversibility by exhibiting Tgel→sol at ∼48 °C and is demonstrated for several cycles. The gel shows an organized network of nanobundles, while that of the sol shows spherical nanoaggregates in microscopy. A bundle with ∼12 nm diameter possessing hydrophobic pockets in itself is obtained from computationally modeled gel, and hence the gel is suitable for storage and release applications. The guest-entrapped gels exhibit the same microstructures as that observed with simple gels, while fluorescence spectra and molecular mechanics suggests that the drug molecules occupy the hydrophobic pockets. All the entrapped drug molecules are released into water, suggesting a complete recovery of the trapped species. The reusability of the gel for the storage and release of the drug into water is demonstrated for four consecutive cycles, and hence the gel formed from G acts as a functional material that finds application in drug delivery.

Topics: Antineoplastic Agents; Calixarenes; Coloring Agents; Curcumin; Diffusion; Doxorubicin; Gels; Materials Testing; Nanocapsules; Phenols; Temperature; Tocopherols

The tremendous therapeutic potential of curcumin as a chemopreventive, antineoplastic and chemosensitizing agent has failed to progress towards clinical development and commercialization due to its unfavorable physicochemical properties, low aqueous solubility, chemical instability, and pharmacokinetics. The present contribution is focused on the feasibility of using PEGylated calixarene, in particular polyoxyethylene-derivatized tert-butylcalix[4]arene, to prepare various platforms for delivery of curcumin such as inclusion complex, supramolecular aggregates, and hybrid liposomal systems. The inclusion complex is characterized by UV-vis and FT-IR spectroscopy as well as thermal gravimetrical analysis and differential scanning calorimetry. At concentrations exceeding the critical micellization concentration of PEGylated calixarene, the tremendous solubility enhancement of curcumin is attributed to additional solubilization and hydrophobic non-covalent interactions of the drug with supramolecular aggregates. A hybrid liposomal system is created via encapsulation of the inclusion complex in dipalmitoylphosphatidylcholine:cholesterol liposomes. Bare and liposomal curcumin:BEC-X inclusion complexes, as well as free curcumin were additionally investigated for cytotoxicity and apoptogenic activity against human tumor cell lines.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Antineoplastic Agents; Apoptosis; Calixarenes; Cell Cycle; Cell Line, Tumor; Cell Survival; Cholesterol; Curcumin; Drug Delivery Systems; Humans; Liposomes; Phenols; Polyethylene Glycols; Solubility