Β-cyclodextrin Nanosponge Research Articles

Controlled Release of the Anticancer Drug Cyclophosphamide from a Superparamagnetic β-Cyclodextrin Nanosponge by Local Hyperthermia Generated by an Alternating Magnetic Field.

A β-cyclodextrin (β-CD) nanosponge (NS) was synthesized using diphenyl carbonate (DPC) as a cross-linker to encapsulate the antitumor drug cyclophosphamide (CYC), thus obtaining the NSs-CYC system. The formulation was then associated with magnetite nanoparticles (MNPs) to develop the MNPs-NSs-CYC ternary system. The formulations mentioned above were characterized to confirm the deposition of the MNPs onto the organic matrix and that the superparamagnetic nature of the MNPs was preserved upon association. The association of the MNPs with the NSs-drug complex was confirmed through field emission scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering, ζ-potential, atomic absorption spectroscopy, X-ray powder diffraction, selected area electron diffraction, and vibrating-sample magnetometer. The superparamagnetic properties of the ternary system allowed the release of CYC by utilizing magnetic hyperthermia upon the exposure of an alternating magnetic field (AMF). The drug release experiments were carried out at different frequencies and intensities of the magnetic field, complying with the "Atkinson-Brezovich criterion". The assays in AMF showed the feasibility of release by controlling hyperthermia of the drug, finding that the most efficient conditions were F = 280 kHz, H = 15 mT, and a concentration of MNPs of 5 mg/mL. CYC release was temperature-dependent, facilitated by local heat generation through magnetic hyperthermia. This phenomenon was confirmed by DFT calculations. Furthermore, the ternary systems outperformed the formulations without MNPs regarding the amount of released drug. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays demonstrated that including CYC within the magnetic NS cavities reduced the effects on mitochondrial activity compared to those observed with the free drug. Finally, the magnetic hyperthermia assays showed that the tertiary system allows the generation of apoptosis in HeLa cells, demonstrating that the MNPs embedded maintain their properties to generate hyperthermia. These results suggest that using NSs associated with MNPs could be a potential tool for a controlled drug delivery in tumor therapy since the materials are efficient and potentially nontoxic.

Design and characterization of nano sponges loaded vaginal gels of Voriconazole

Objectives: The current inquiry of this research job is to build and analyze a bio adhesive vaginal gel that is packed with Voriconazole Nano sponge for an extended residence duration at the point of infection, resulting in a positive drug release profile. Methods: Nano sponges were created using a solvent evaporation process in varied Voriconazole to β-cyclodextrin ratios. Zeta possibility, polydispersity, size of particles analysis, capture efficiency, and surface morphology of Nao sponges are all determined using scanning microscopes with electrons (SEM). FTIR and DSC investigations were used to determine drug excipient compatibility. Carbopol/Hypromellose/Sodium Carboxymethyl cellulose/HPC has been used to make the bio adhesive gel, while both propyl paraben and a methyl para were employed as antioxidants. Triethanolamine, also was used to regulate the pH, resulting in a transparent gel. The gel base has been incorporated with the improved Voriconazole Nano sponge mixture. The pH, viscosity, spread ability, extrudability, and medication content of Nano sponge in mixes of gels were all investigated. The gel's in vivo diffusion has been examined on goat vaginal mucosal. Cellophane membranes was used in an artificial drug release examination. Results: The improved generation of IDLNS12 Nano sponge (drug-polymer ratio 1:1) demonstrated 91.56% entrapment efficiency. The average particle diameter of all formulations was less than 310 nm. The SEM photographs revealed smooth and spherical particles. INSG4 (Carpool and HPC) gel formulation had a viscosity value of 4529 cps at 2-10 RPM, a gel strength of 92.65N load, and an expansion speed of 37.24 g.cm/seconds. At 12.0 minutes, INSG4 achieved 99.98% drug release. And a mucous adhesive time of in excess of 12 hours. Conclusion: These results suggest that Voriconazole-loaded β-cyclodextrin Nano sponge in mucous adhesive gel might be used for managing infections of vagina perpetually.

Click nanosponge – A novel amine-rich β-cyclodextrin-based crosslinked polymer for heterogeneous catalysis

Cyclodextrin-based nanosponges are promising materials for heterogeneous catalysis due to their inherent synthetic versatility, tunable porosity and nontoxicity. In this work, a primary amine-rich β-cyclodextrin nanosponge was synthesized via click imine condensation reaction between 1,6-hexamethylamine-functionalized β-cyclodextrin (CDAM) and glutaraldehyde (GLT) to afford CDGLAM, in mild conditions. The crosslinked polymer exhibited a BET surface area of 36.39 m2 g−1, an average pore diameter of 3.09 nm (as assessed by the BJH method), and thermal stability up to 253 °C. CDGLAM was tested as heterogeneous catalyst for the metal-free Henry and Knoevenagel reactions, between aromatic aldehydes and nitromethane or ethyl cyanoacetate, respectively, affording the products in moderate to very high yields. These results show the ease of preparation of β-CD-based nanosponges from a green chemistry perspective, as well as their potential for future use in catalytic systems.

Incorporation of exemestane into ternary nanosponge system for enhanced anti-tumor potential in breast cancer

The present investigation reports the potential of exemestane loaded cyclodextrin based nanosponges for the treatment of breast cancer. Fourier transform infrared, and nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the encapsulation of ring B, C, and D of exemestane in the nanosponge cavity. In vitro studies demonstrated a 6.58-folds increase in the aqueous solubility and a 1.76-folds increase in the dissolution of exemestane in the optimized nanosponge formulation EF2. It also exhibited enhanced cytotoxicity in MCF-7 cell line. Pharmacokinetic studies revealed a 1.37-fold increase in C max and a 2.10-fold increase in oral bioavailability of EF2, as compared to its marketed product Aromasin®. Concomitantly, this nano-formulation reduced the tumor burden to 45.71% in a DMBA-induced breast cancer rat model. This EF2-treatment also improved the hematological parameters of the animals. Histopathology of breast tissue also presented reduction in characteristic cytoarchitectural features of breast tumor. In vivo toxicity studies demonstrated reduced hepatotoxicity of the nanosponge formulation when compared with Aromasin®. These results were further supported by histological studies of excised liver tissues, where the size of hepatocytes in EF2-treated animals was like the normal hepatocyte size. In conclusion, the encapsulation of exemestane in β-cyclodextrin nanosponge along-with HPMC E5 improved its aqueous solubility, bioavailability, and ultimately therapeutic efficacy for the treatment of breast cancer.

Ferulic acid grafted into β-cyclodextrin nanosponges ameliorates Paraquat-induced human MRC-5 fibroblast injury.

Paraquat (PQ) is a commercially important and effective herbicide in the world. Nevertheless, it has higher toxicity causing acute organ damage and different complications, mainly in the lungs and kidneys. Ferulic acid (FA), 4-hydroxy-3-methoxycinnamic acid imposes multiple pharmacological impacts. No protective effect of FA on PQ poisoning-caused human embryonic lung fibroblast damage has not been reported. Despite their many beneficial effects, FA is characterized by poor water solubility, low bioavailability, and phytochemical instability. To solve the problem, β-cyclodextrin nanosponge (β-CD NSs) was utilized to increase the solubility of FA so that it was grafted into β-CD NSs to establish β-CD@FA NSs. The purpose of this work was to examine for the first time the protective effect of β-CD@FA NS on MRC-5 human lung cells damages induced by PQ poisoning. MTS assay was performed to investigate the viability of MRC-5 cells at different concentrations of FA/β-CD@FA NSs when cells were co-cultured with 0.2 μg/mL PQ. The flow cytometry study was carried out to determine apoptosis. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were detected using appropriate biochemistry kits. Compared with the PQ group, the cell activity, CAT, and SOD levels were significantly increased in the FA and chiefly in β-CD@FA NSs intervention groups, whereas apoptosis and MDA levels were markedly decreased. The inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 22 (IL-22) were detected. The results demonstrate that β-CD@FA NSs can inhibit PQ-induced cell damage by enhancing antioxidant stress capacity and regulation of inflammatory responses.

Synthesis and Characterization of Magnetite/Gold Core Shell Nanoparticles Stabilized with a β-Cyclodextrin Nanosponge to Develop a Magneto-Plasmonic System

Magnetite/gold core-shell nanoparticles (magnetite/gold NPs) have important optical and magnetic properties that provide potential for applications, especially biomedical ones. However, their preparation is not exempt from difficulties that might lead to unexpected or undesired structures. This work reports the synthesis and characterization of magnetite/gold NPs using tetramethylammonium hydroxide (TMAH) to promote the formation of a continuous interface between the magnetite core and the thin gold shell. The synthesized magnetite/gold NPs were characterized using transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS), field emission scanning electron microscope (FE-SEM), ζ-potential, vibrating sample magnetometer (VSM), selected area electron diffraction (SAED), UV-Visible spectroscopy, and dynamic light scattering (DLS), confirming the core-shell structure of the NPs with narrow size distribution while evidencing its plasmonic and superparamagnetic properties as well. Further, the magnetite/gold NPs were associated and stabilized with a β-cyclodextrin nanosponge (β-CDNSs), obtaining a versatile magneto-plasmonic system for potential applications in the encapsulation and controlled release of drugs.

Palladated Cyclodextrin Nanosponge-Alginate Dual Bead as an Efficient Catalyst for Hydrogenation of Nitroarenes in Aqueous Solution.

In this study, we present a novel composite material consisting of β-cyclodextrin nanosponge and sodium alginate, used as a support for the immobilization of palladium (Pd) nanoparticles. The composite alginate-cyclodextrin nanosponge beads were prepared, taking advantage of the 3D polymeric network and β-cyclodextrin cavity of the nanosponge. These beads exhibited excellent encapsulation capabilities for hydrophobic substrates, allowing their transfer in aqueous media. The cyclodextrin nanosponge served as a stabilizer for Pd nanoparticles and facilitated phase transfer. Additionally, the sodium alginate bead contributed to the robustness of the structure and improved the recovery and recyclability of the composite material. Comparative studies with control catalysts confirmed the beneficial effect of incorporating cyclodextrin nanosponge within alginate beads, particularly for more hydrophobic substrates. Optimization of reaction conditions revealed that employing 0.03 g of catalyst per mmol of nitroarene at 45 °C resulted in the maximum yield within 90 min. Evaluation of the substrate scope demonstrated the hydrogenation capability of various substrates with different electronic properties under the developed protocol. Notably, the nitro group was selectively reduced in substrates featuring competing functionalities. Furthermore, the recyclability and stability of the composite catalyst were confirmed, making it a promising candidate for sustainable catalysis.

Enhancement in the therapeutic potential of lapatinib ditosylate against breast cancer by the use of β-cyclodextrin based ternary nanosponge system

The present investigation was performed to demonstrate the therapeutic potential of lapatinib ditosylate (LD) loaded nanosponge for the treatment of breast cancer. The study reports the fabrication of nanosponge by reaction of β-cyclodextrin with a cross-linking agent, diphenyl carbonate, at several molar ratios using the ultrasound-assisted synthesis method. The drug was loaded into the rightest nanosponge by lyophilization with and without 0.25% w/w polyvinylpyrrolidone. The significantly reduced crystallinity of developed formulations was established by differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). Morphological changes of LD, and formulations were compared by scanning electron microscopic (SEM) technique. Fourier transform infrared (FT-IR), and nuclear magnetic resonance (NMR) spectroscopic analysis were performed to establish the interacting groups of the host and guest molecules. It revealed interaction of the quinazoline ring, furan ring, and chlorobenzene functionality of LD with the hydroxyl group of β-cyclodextrin based nanosponge. Similar predictions were also obtained during their in-silico analysis. Saturation solubility and in vitro drug release studies revealed a 4.03-fold, and 2.43-fold rise in aqueous solubility, and dissolution of LD in the optimized formula (F2). The MCF-7 cell line study, too, revealed the higher efficiency of nanosponge formulations. The in vivo pharmacokinetic studies of optimized formulation illustrated 2.76-times, and 3.34-times enhancements in Cmax and oral bioavailability, respectively. Concomitant results were obtained during the in vivo studies performed using DMBA-induced breast cancer models in female Sprague Dawley rats. The tumor burden was found to be reduced to approximately 60% by the use of F2. The hematological parameters of animals treated with F2 were also improved. Histopathology of breast tissue excised from an F2-treated rat showed a reduced size of ductal epithelial cells associated with shrunken cribriform structures and cross-bridges. The in vivo toxicity studies also showcased reduced hepatotoxicity of the formulation. Altogether, it can be concluded that encapsulation of lapatinib ditosylate in β-cyclodextrin nanosponge has improved aqueous solubility, bioavailability and, in turn, therapeutic efficacy.

Comparative evaluation of dithranol-loaded nanosponges fabricated by solvent evaporation technique and melt method

BackgroundDithranol, a standard drug for psoriasis, has lured keen attention by virtue of its antioxidant, anti-proliferative and anti-inflammatory activities. However, its poor stability and solubility critically impair the formulation design, evaluation and administration. To improve these issues, dithranol was encased in β-cyclodextrin nanosponges using solvent evaporation technique. Previously, nanosponges containing dithranol were developed in our laboratory using melt technique. Herein, a comparison of nanosponges prepared by both techniques was also included.ResultsDifferent nanosponge batches were engineered using diphenyl carbonate as cross-linker with β-cyclodextrin as polymer employing solvent evaporation technique. Dithranol was loaded in nanosponges via lyophilization. Fourier transform infrared spectroscopy, differential scanning colorimeter and powdered X-ray diffraction studies confirmed successful encapsulation and complexation of this drug in β-cyclodextrin nanosponges. The effect of a variable amount of cross-linker on the solubility, encapsulation efficiency, zeta potential, particle size and polydispersity index was evaluated in fabricated nanocarriers. Further, β-cyclodextrin nanosponge batches were subjected to solubility studies, photostability examination and antioxidant activity analysis and compared with previously prepared dithranol-loaded nanosponges. From the present studies results, it was concluded that dithranol-loaded nanosponges using solvent evaporation technique not only improved solubility and photostability but also preserved the antioxidant efficacy of the chosen drug.ConclusionThe overall results emphasized moral guidance concerning encapsulation, evaluation and characterization and accredited dithranol solubilization, photostability and antioxidant potential. However, solvent evaporation and melt method are easy and promising methods to fabricate nanosponges for dithranol. This comparative study demonstrated the parameters which were affected by chosen techniques. Further, from the results of present studies, it was concluded that the formulation scientists should select the preparation technique based on the objective of their research work and requirement of desired features.Graphical abstract

Structural Adaptive, Self-Separating Material for Removing Ibuprofen from Waters and Sewage.

β-Cyclodextrin nanosponge (β−CD−M) was used for the adsorption of ibuprofen (IBU) from water and sewage. The obtained material was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET), Barrett–Joyner–Halenda (BJH), Harkins and Jura t-Plot, zeta potential, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and elementary analysis (EA). Batch adsorption experiments were employed to investigate the effects of the adsorbent dose, initial IBU concentration, contact time, electrolyte ions and humic acids, and sewage over adsorption efficiency. The experimental isotherms were show off using Langmuir, Freundlich, Hill, Halsey and Sips isotherm models and thermodynamic analysis. The fits of the results were estimated according to the Sips isotherm, with a maximum adsorption capacity of 86.21 mg g−1. The experimental kinetics were studied by pseudo-first-order, pseudo-second-order, Elovich, modified Freundlich, Weber Morris, Bangham’s pore diffusion, and liquid film diffusion models. The performed experiments revealed that the adsorption process fits perfectly to the pseudo-second-order model. The Elovich and Freundlich models indicate chemisorption, and the kinetic adsorption model itself is complex. The data obtained throughout the study prove that this nanosponge (NS) is extremely stable, self-separating, and adjusting to the guest structure. It also represents a potential biodegradable adsorbent for the removal IBU from wastewaters.

Direct monitoring of diclofenac using a supramolecular fluorescent approach based on β-cyclodextrin nanosponge

β-cyclodextrin cross-linked polymer was prepared with pyromellitic anhydride as a cross-linker and acted for the facile fluorescence recognition. The fluorescence studies exhibited that the probe has an outstanding affinity to diclofenac and can select it in the presence of morphine, ibuprofen, codeine, and amphetamine at the emission wavelength around 423 nm. The fluorescence enhancement process was completed in the optimum pH 7 and response time 1.2 min. The detection limit and linear range, were 0.92 µM and 1–33 µM, respectively. The UV–Vis absorption spectra tracing were proved the static enhancement mechanism for the interaction between nanosponge and diclofenac. Interestingly, the probe can be utilized as a feasible method for the measurement of diclofenac in commercially available tablets.

Nanosponges as protein delivery systems: Insulin, a case study.

Cyclodextrin-based nanosponges have been found to bepromising drug delivery systems. This paper investigates an application that still needs to be studied in depth, that is, the oral delivery of peptides and proteins, choosing insulin as a case study. The nanospongewas synthesized by crosslinkingβ-cyclodextrins withpyromellitic dianhydride, adopting a top-down approach for its subsequent formulation. Aphysicochemical characterization, in-vitro andin-vivo tests were carried out on the formulation developed. It was nanometric (around 250nm) with high negative zeta potential, mucoadhesion and swelling properties, good loading capability (about 14%) and encapsulation efficiency (above 90%). The in-vitro release of insulin was negligible at a gastric pH (below 2%) while sustained at an intestinal pH, thus showing a pH-sensitive behaviour of the nanosponge. The Caco-2 cell permeability assay proved that the intestinal permeation of insulin was enhanced when loaded inside the nanosponge. The in-vivo studies confirmed the presence of insulin in rat plasma and a marked hypoglycemic effect in diabetic mice after duodenal and oral administrations, respectively. These preliminary results are encouraging with a view to continuing to study this β-cyclodextrin nanosponge technology for the oral administration of insulin and extending this approach to other proteins of pharmaceutical interest.

Hyper-cross-linked β-cyclodextrin nanosponge: a three-dimensional, porous and biodegradable catalyst in the one-pot synthesis of kojic acid-based heterocyclic compounds

In the present study, β-cyclodextrin-based nanosponges were prepared by reaction of β-cyclodextrin with dicarbonyl imidazole as a crosslinker agent. The synthesized polycarbonate nanosponge was characterized by FT-IR spectroscopy, thermogravimetric analysis, scanning electron microscopy and Brunauer–Emmett–Teller. The catalytic activity of β-cyclodextrin-based nanosponges was successfully tested in the one-pot three-component condensation of kojic acid, aromatic aldehydes and various aromatic amines. The superiority of this new strategy is short reaction times, high yields and utilizing of biodegradable and nontoxic nanocatalyst.

β-Cyclodextrin nanosponge polymer: a basic and eco-friendly heterogeneous catalyst for the one-pot four-component synthesis of pyranopyrazole derivatives under solvent-free conditions

β-Cyclodextrin-epichlorohydrin nanosponge polymer, β-CD/EP, was prepared from the stepwise polymerization of β-cyclodextrin with epichlorohydrin under basic conditions and characterized by FT-IR spectroscopy, thermogravimetric analysis, scanning electron microscopy and Brunauer–Emmett–Teller. An efficient synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] and pyranopyrazole derivatives is described using β-CD/EP as a stationary micro-vessel and basic heterogeneous catalyst via a four component reaction under solvent-free conditions.

Biofunctionalization of β-cyclodextrin nanosponges using cholesterol

Cyclodextrins nanosponges (CD-NSPs) are highly microporous crosslinked polymers with potential applications in the delivery of small and macro-molecular therapeutic agents. Despite the potent host-guest inclusion property, their inherent lack of cellular binding ability has limited applications in drug delivery. Herein, we functionalized the surface of β-cyclodextrin nanosponge (β-CD-NSP) with cholesterol, which is endogenous physiological molecules, widely distributed in all cells, and responsible for cell interactions and protein binding. The surface grafting of synthesized β-CD-NSP was confirmed with spectroscopic, microscopic, thermogravimetric, and chromatographic techniques. Moreover, β-CD-NSP was found to be safe in cytotoxicity assay. Doxorubicin (Dox) was selected as a model drug for drug adsorption study of cholesterol hydrogen succinate (CHS) grafted β-CD-NSP. The cellular uptake of NSP was found to be enhanced after CHS modification confirmed by confocal laser scanning microscopy (CLSM). Thus, proposed CHS modified β-CD-NSP system could be used as a site-specific drug delivery carrier.

Glutathione Bioresponsive Cyclodextrin Nanosponges.

Invited for this month's cover is Prof. Francesco Trotta's group from the University of Torino, Italy. The cover picture shows the chemical structure of a glutathione-responsive β-cyclodextrin nanosponge, bearing disulfide bridges and loaded with anticancer doxorubicin (red and white pills). Glutathione thiol groups are able to reduce the nanosponge disulfide moieties. The cleavage of the disulfide bridges allows a targeted release of anticancer drugs into glutathione-rich chemoresistant tumor cells. Read the full text of the article at 10.1002/cplu.201500531.

In Vitro and In Vivo Therapeutic Evaluation of Camptothecin-Encapsulated β-Cyclodextrin Nanosponges in Prostate Cancer.

Camptothecin (CPT), a pentacyclic alkaloid, is an inhibitor of DNA Topoisomerase-I and shows a wide spectrum of anti-cancer activities. The use of CPT has been hampered by poor aqueous solubility and a high degradation rate. Previously, it has been reported that CPT encapsulated in β-cyclodextrin-nanosponges (CN-CPT) overcomes these disadvantages and improves the CPT's inhibitory effect on DU145 prostate tumor cell lines, and PC-3 growth in vitro. This work extends these observations by showing that CN-CPT significantly inhibits the adhesion and migration of these tumor cells and their STAT3 phosphorylation. The anti-adhesive effect is exerted also in human endothelial cells, in which CN-CPT also inhibits the angiogenic activity as assessed by the tubulogenesis and sprouting assays. Finally, CN-CPT substantially delays the growth of PC-3 cell engraftment in SCID mice in vivo without apparent toxic effects. These results support the use of β-cyclodextrin nanosponge nanotechnology as a potential nanocarrier for delivery of anticancer drugs in the treatment of prostate cancers.

Potential of erlotinib cyclodextrin nanosponge complex to enhance solubility, dissolution rate, in vitro cytotoxicity and oral bioavailability

The present study was envisaged to evaluate the effect of erlotinib β-cyclodextrin nanosponge (ERL-NS) on the solubility, dissolution, in vitro cytotoxicity and oral bioavailability of erlotinib (ERL). Preliminary studies were conducted to select the optimized stoichiometry concentration of ERL and NS. The drug nanosponge complex comprising of 1:4 proportions of ERL and NS was prepared by freeze drying. ERL-NS formed nanoparticles of 372±31nm size with narrow size distribution (0.21±0.07 PDI) and high zeta potential (−32.07±4.58mV). The complexation phenomenon was confirmed by DSC, SEM, PXRD, FTIR, and TEM studies. In vitro dissolution studies revealed an increased dissolution rate (2-folds) with an enhanced dissolution efficiency of the nanosponge complex in comparison to pure drug. In vitro cytotoxicity study and apoptosis assay in pancreatic cell lines (MIA PaCa-2 and PANC-1) indicates the increased toxicity of ERL-NS. Both, quantitative and qualitative cell uptake studies unveiled the higher uptake efficiency of ERL-NS than free drug. ERL-NS showed enhanced oral bioavailability with 1.8-fold higher Cmax (78.98±6.2 vs. 42.36±1.75μg/ml), and ∼2-fold AUC0−∞ (1079.95±41.38 vs. 580.43±71.91), in comparison to pure ERL. Therefore, we conclude that the formation of a complex of nanosponge with ERL is a successful approach to increase its solubility, dissolution and oral bioavailability which may ultimately result in reduction in dose and dose related side-effects.

β-Cyclodextrin Nanosponges as Multifunctional Ingredient in Water-Containing Semisolid Formulations for Skin Delivery

A β-cyclodextrin nanosponge cross-linked with pyromellitic dianhydride (βNS-PYRO) is reported for the first time as multifunctional ingredient in semisolid formulations for drug delivery to the skin. The role of βNS-PYRO on solubilization and stabilization of the photosensitizer benzoporphyrin-derivative monoacid ring A (BPDMA) and all-trans retinoic acid (atRA) as well as its effect on skin permeation of diclofenac (DIC) was investigated. Aqueous solutions, gels, and cream-gels were prepared from mixtures of βNS-PYRO with a conventional gelling agent at specific ratios. The incorporation of BPDMA in βNS-PYRO water solutions prevented its aggregation and gave kinetically stable complexes with high photostability and singlet oxygen generation upon irradiation. atRA incorporated in the βNS-PYRO-containing gel demonstrated a remarkable stability as compared with the formulation without βNS-PYRO, resulting in an eightfold increase of its lifetime. Skin permeation studies highlighted that βNS-PYRO in gels and cream-gels containing DIC significantly decreased the amount of drug permeated through the skin while increasing its amount in stratum corneum and viable epidermis. Overall, swellable βNS-PYRO turns to be a multifunctional coingredient with potential in topical monophasic and biphasic formulations to stabilize light-sensitive drugs and to localize the action of highly penetrating drugs in the external layers of skin.

Nanosponge-encapsulated camptothecin exerts anti-tumor activity in human prostate cancer cells

Camptothecin (CPT) is a potent DNA Topoisomerase I inhibitor with anti-tumor activity in hematological and solid tumors. However, it did not reach clinical use because of its poor solubility and high degrability. β-Cyclodextrin nanosponge (CN) have been demonstrated to be able to increase the solubility of lipophilic compounds and to protect them from degradation. In the present study, we evaluated whether β-Cyclodextrin nanosponge carriers can overcome CPT chemical disadvantages and improve the in vitro anti-tumor efficacy in the androgen refractory models of prostate cancer DU145 and PC-3 and the androgen sensitive model LNCaP. Camptothecin-loaded β-Cyclodextrin nanosponge (CN-CPT) showed sizes of about 400nm, spherical shape and a drug loading of 38%. HPLC analysis, performed on the cell pellet after treatment with CN-CPT revealed that CPT concentration increased over time indicating a prolonged release of the drug. Moreover, CN-CPT inhibited Topoisomerase I activity, and induced DNA damage, and cell cycle arrest more effectively than CPT, indicating that the CN-CPT formulation does not affect activity of the drug. Moreover, Annexin V/Propidium Iodide staining showed an induction of cell death at low concentrations that were not effective for CTP. LNCaP cells were less sensitive to CPT than PC-3 and DU145 cells, but CN-CPT still exerted higher anti-proliferative activity and DNA damage ability than CPT. The experiments performed in LNCaP cells demonstrated that CN-CPT treatment inhibited expression of the androgen receptor at doses where CPT was ineffective. Our results demonstrated the higher anti-tumor effectiveness of CN-CPT compare to CPT in prostate cancer cells, supporting the relevance of future studies for the use of the β-Cyclodextrin nanosponge to deliver anticancer drugs in vivo.