Cyclodextrin-based Nanosponges Research Articles

Wave-Assisted Techniques, a Greener and Quicker Alternative to Synthesis of Cyclodextrin-Based Nanosponges: A Review.

The ever-increasing applications of cyclodextrin and cyclodextrin-based nanosponges in formulation development has gained much attention from researchers towards needed research in this arena. Nanosponges are three-dimensional nanoporous versatile carriers in the pharmaceutical research field because of their capability to encapsulate lipophilic and hydrophilic drugs both in their crystalline structure by inclusion and non-inclusion phenomenon. This review sheds light on the advancements made in this field and the associated patents with regard to their synthesis while zooming in on the utilization of two novel energies (Microwave and ultrasonic) in accomplishing this goal and its future thereof. Microwave and ultrasound-assisted manufacturing of cyclodextrin-based nanosponges (CDNS) has been found superior to conventional heat-dependent methods due to rapid/homogenous heating and fast kinetics, which ultimately provide the final product with high yield and crystallinity relatively rapidly. The review article also defines several facets of microwave and ultrasound-assisted nanosponge synthesis including the synergism of microwave and ultrasonic energy and the theories behind them. This hitherto unexplored microwave-ultrasonic coupling technology could be a future technology to synthesize CD-NS with a better outcome. In the recent past, these novel energy processes have been used successfully in material synthesis at an industrial scale due to their swift and streamlined synthesis attributes. Likewise, these wave-assisted methods have the full potential to materialize the concept of CD-NS from lab scale to industrial scale as a competent and versatile drug carrier, having all the prerequisite characteristics, for commercialization.

Unleashing the potential of cyclodextrin-based nanosponges in management of colon cancer: A review

Unleashing the potential of cyclodextrin-based nanosponges in management of colon cancer: A review

Exploring Cyclodextrin-Based Nanosponges as Drug Delivery Systems: Understanding the Physicochemical Factors Influencing Drug Loading and Release Kinetics.

Cyclodextrin-based nanosponges (CDNSs) are complex macromolecular structures composed of individual cyclodextrins (CDs) and nanochannels created between cross-linked CD units and cross-linkers. Due to their unique structural and physicochemical properties, CDNSs can possess even more beneficial pharmaceutical features than single CDs. In this comprehensive review, various aspects related to CDNSs are summarized. Particular attention was paid to overviewing structural properties, methods of synthesis, and physicochemical analysis of CDNSs using various analytical methods, such as DLS, PXRD, TGA, DSC, FT-IR, NMR, and phase solubility studies. Also, due to the significant role of CDNSs in pharmaceutical research and industry, aspects such as drug loading, drug release studies, and kinetics profile evaluation of drug-CDNS complexes were carefully reviewed. The aim of this paper is to find the relationships between the physicochemical features and to identify crucial characteristics that are influential for using CDNSs as convenient drug delivery systems.

Formulation and Evaluation of Nanosponge-based Drug Delivery System of Aceclofenac for Topical application

A transdermal drug delivery system using nanosponge and BCS class II drug, Aceclofenac (ACE) was achieved using xerogel as a final dosage form. Blank Beta Cyclodextrin based nanosponge (CDNS) were loaded with aceclofenac to formulate ACE loaded CDNS not only can be effectively treated for osteoarthritis but also successfully evaluated using ex vivo skin permeation studies. Methods used for formulation of ACE loaded CDNS were found out to be effective and accomplished 89.29±2.59% drug entrapment. The optimized formulation had % drug loading of 72.16±3.13%. The zeta potential of the ACE-loaded CDNS was found to be -27.3±1.1mV. A zeta potential value close to ±30mV indicates good physical stability of the micro particles on account of electrostatic repulsion. ACE-loaded CDNS released more than 90% drug in just 150mins (2.5hrs) whereas the marked formulation and ACE drug released more than 90% drug in 240mins (4hrs) and 330mins (5.5hrs) respectively. The conclusion of the current work can be drawn as ACE-loaded CDNS based gel has the potential to improve the transdermal bioavailability of aceclofenac against osteoarthritis with less adverse actions.

Cyclodextrin-based nanosponges as promising carriers for active pharmaceutical ingredient.

Effective drug distribution at the intended or particular location is a critical issue that researchers are now dealing. Nanosponges have significantly increased in importance in medication delivery using nanotechnology in recent years. An important step toward solving these problems has been the development of nanosponges. Recently created and proposed for use in drug delivery, nanosponge is a unique type of hyper-crosslinked polymer-based colloidal structures made up of solid nanoparticles with colloidal carriers. Nanosponges are solid porous particles that may hold pharmaceuticals and other actives in their nanocavities. They can be made into dosage forms for oral, parenteral, topical, or inhalation use. The targeted distribution of drugs in a regulated manner is greatly aided by nanosponge. The utilization of nanosponges, their benefits, their production processes, the polymers they are made of, and their characterization have all been covered in this review article.

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.

Novel Trend: Magic Bullet To Nanomedicine As Targeted Drug Delivery -Nanosponges

Effective medication delivery at a specific location has made it possible to carry out the intended task of controlling release rates and have better compliance with the healthcare system, but the chemistry's complex form has complicated things. However, the development of nanosponges has provided a key solution to this issue. Nanosponges are extremely tiny sponges that are roughly the size of a virus and can contain a range of medications. These sponges can move throughout the body until they interact with a particular target spot, attach to the surface, and begin to release drugs under regulated circumstances. Some cyclodextrin-based nanosponges have been proposed as nano-delivery systems, and they produce porous, insoluble nanoparticles with crystalline and amorphous natures. The solubility of these sponges in liquids is a crucial property.

Multifunctional Drug Delivery System: Nanosponges.

In recent years, nanotechnology has been the focus of study for the cure of different diseases, among which nanosponge delivery system is one of a kind. Nano sponges are tiny, highly porous, three-dimensional nanostructures with a size range of 250nm-1µm in an amorphous or crystalline structure. Nanosponges usually act as an excipient or carrier of a drug in the different delivery systems. The type of polymers and cross-linkers, along with their concentration ratio, causes variation in nanosponges's dimension and encapsulation efficiency. Nanosponges have gained prominence in recent times due to their distinct ability to encapsulate both hydrophilic and lipophilic drugs within their internal cavity, thereby improving the solubility of drugs that have low water solubility. Virus-like size helps the nanosponges to circulate within the body without getting eliminated by the immune system until they stick to the targeted part of the body, which makes it the perfect candidate for a targeted drug delivery system and controlled delivery system as well because of its slow drug release property for a more extended period. Cyclodextrin-based nanosponges are the best choice for anticancer drug delivery as their small virus-like diameter helps them in passive targeting by enhancing the enhanced permeability and retention effect, allowing the anticancer drug to stay inside the tumour cell to show more significant therapeutic action on cancer, while for active targeting to the cancerous cell, nanosponges are attached with a ligand on it for receptor binding purpose. It can be used for drug delivery in many major diseases like brain-related diseases, diabetes, cancer, fungal, hypertension, etc., in different dosage forms, like oral, topical, hydrogel, parenteral, etc.

Cyclodextrin Nanosponges: A Revolutionary Drug Delivery Strategy.

Nanosponges are porous solid cross-linked polymeric nanostructures. This study focuses on cyclodextrin-based nanosponges. Nanosponges based on cyclodextrin can form interactions with various lipophilic or hydrophilic compounds. The release of the entrapped molecules can be altered by altering the structure to obtain either a longer or faster release kinetics. The nanosponges might increase the aqueous solubility of weakly water-soluble compounds, develop long-lasting delivery systems, or construct novel drug carriers for nanomedicine. CD-NS (cyclodextrin-based nanosponges) are evolving as flexible and promising nanomaterials for medication administration, sensing, and environmental cleanup. CD-NS are three-dimensional porous structures of cyclodextrin molecules cross-linked by a suitable polymeric network, resulting in a large surface area. This overview covers CD-NS synthesis methods and applications.

Cyclodextrin Inclusion Complexes for Improved Drug Bioavailability and Activity: Synthetic and Analytical Aspects.

Many active pharmaceutical ingredients show low oral bioavailability due to factors such as poor solubility and physical and chemical instability. The formation of inclusion complexes with cyclodextrins, as well as cyclodextrin-based polymers, nanosponges, and nanofibers, is a valuable tool to improve the oral bioavailability of many drugs. The microencapsulation process modifies key properties of the included drugs including volatility, dissolution rate, bioavailability, and bioactivity. In this context, we present relevant examples of the stabilization of labile drugs through the encapsulation in cyclodextrins. The formation of inclusion complexes with drugs belonging to class IV in the biopharmaceutical classification system as an effective solution to increase their bioavailability is also discussed. The stabilization and improvement in nutraceuticals used as food supplements, which often have low intestinal absorption due to their poor solubility, is also considered. Cyclodextrin-based nanofibers, which are polymer-free and can be generated using environmentally friendly technologies, lead to dramatic bioavailability enhancements. The synthesis of chemically modified cyclodextrins, polymers, and nanosponges based on cyclodextrins is discussed. Analytical techniques that allow the characterization and verification of the formation of true inclusion complexes are also considered, taking into account the differences in the procedures for the formation of inclusion complexes in solution and in the solid state.

Cyclodextrin-Based Nanosponges as an Environmentally Sustainable Solution for Water Treatment: A Review

Cyclodextrin-Based Nanosponges as an Environmentally Sustainable Solution for Water Treatment: A Review

β-cyclodextrin-based nanosponges for crocetin delivery: Physicochemical characterization, aqueous solubility, and bioactivity

Crocetin (CRT) is a natural carotenoid compound with promising health benefits but its use is restricted because of the poor aqueous solubility. Therefore, cyclodextrin-based nanosponges (CDNSs), a kind of water-soluble supramolecular macrocyclic polymer, was employed to load CRT for improving the solubility. The β-CDNSs with different molar ratio of β-CD and crosslinker were synthesized and β-CDNS 1:8 was chosen. The loading capacity (LC) and complexation efficiency (CE) of prepared CRT-loaded β-CDNS were about 17.92% and 94.64%. The formation of inclusion and non-inclusion structure of CRT-loaded β-CDNS was confirmed by different techniques. The surface properties and dispersibility were also studied. Besides, the water solubility of CRT was significantly increased to 7.27 μg/mL. The antioxidant activity of CRT was enhanced. The in vitro cytotoxicity of CRT for normal cells was reduced and for tumor cells was increased through the loading of β-CDNS. In summary, this work demonstrated β-CDNS could be used for the delivery of CRT and promote the application of CRT in many fields.

DEVELOPMENT AND EVALUATION OF NANOSPONGES-BASED BUCCAL TABLETS FOR DELIVERY OF QUERCETIN USING BOX-BEHNKEN DESIGN

Objective: The goal was to develop a controlled-release formulation of quercetin utilizing the cyclodextrin-based nano-sponges as a nanocarrier. Methods: Based on the preliminary trials a 3-factor, 3-level Box-Behnken design was employed. Five types of nano-sponges from β-cyclodextrin (NS1-NS5) were purposely designed. Quercetin was loaded into nano-sponges by freeze-drying method. The prepared nano-sponges were characterized and formulated into tablets and evaluated for weight variation, hardness, friability, disintegration studies, dissolution and stability studies. Results: The particle sizes of quercetin-loaded nano-sponges are in between 36.45 to 135.27 nm, encapsulation efficiency of 42.37 to 88.44 % and drug release% at 6h of 53.04 to 82.64 %. In vitro release studies showed that more than 90 % of drugs were released from nano-sponge formulations as compared to only around 45% from free drug suspension after 24 h. The FTIR, DSC and XRPD studies confirmed the interaction of Quercetin with nano-sponges. TEM image revealed the spherical structure of drug-loaded nano-sponges. The drug loaded in the nano-sponge structure can be retained and released slowly over time. The nano-sponges were formulated into tablets and evaluated for weight variation, hardness, friability and disintegration studies and obtained satisfactory results. In vitro drug release from a tablet exhibited a maximum release of 99.75 percent with controlled release behaviour over 24 h, and stability studies suggested no major significant changes within 6 mo. Conclusion: Cyclodextrin-based nano-sponges showed superior complexing ability with increased solubility of poorly soluble Quercetin tablets made for controlled drug delivery, which can reduce dosing frequency.

Reduced graphene oxide/silver nanoparticles/β-cyclodextrin nanosponges composites with improved photocatalytic activity

Significant activity improvement was achieved by associating graphene oxide-silver composite photocatalysts with cyclodextrin-based nanosponge materials, due to the synergistic effect provided by the supramolecular host abilities of the nanosponge. Three photocatalysts were prepared, fully characterized (FT-IR, ss-NMR, Raman, XRD, SEM, EDX, AFM, ICP, TGA, potentiometric titration), and tested for the oxidative photodegradation of some dyes and phenols, chosen as model organic pollutants. Compared to the unsupported photocatalyst, the nanosponge-based materials showed enhanced performances (being able to carry out the degradation even of dyes which do not react in the presence of the unsupported catalyst), and good recyclability. The activity improvement is attributed to a local concentration effect provided by the nanosponge, able to capture the organic substrate in the proximity of the actual photocatalyst. The results presented herein provide a helpful basis for designing advanced catalytic systems.

Optimisation of a Greener-Approach for the Synthesis of Cyclodextrin-Based Nanosponges for the Solubility Enhancement of Domperidone, a BCS Class II Drug.

BCS class II molecules suffer from low oral bioavailability because of their poor permeability and sub-optimal aqueous solubility. One of the approaches to enhance their bioavailability is using cyclodextrin-based nanosponges. This study aimed to optimise and evaluate the feasibility of a microwave-assisted approach to synthesise nanosponges and improve domperidone's solubility and drug delivery potential. In the production process, microwave power level, response speed, and stirring speed were optimised using the Box-Behnken approach. Ultimately, the batch with the smallest particle size and highest yield was chosen. The optimised method of synthesis of the nanosponges resulted in a product yield of 77.4% and a particle size of 195.68 ± 2.16 nm. The nanocarriers had a drug entrapment capacity of 84 ± 4.2% and a zeta potential of -9.17± 0.43 mV. The similarity and the difference factors demonstrated proof-of-concept, showing that the drug release from the loaded nanosponges is significantly greater than the plain drug. Additionally, spectral and thermal characterisations, such as FTIR, DSC, and XRD, confirmed the entrapment of the drug within the nanocarrier. SEM scans revealed the porous nature of the nanocarriers. Microwave-assisted synthesis could be used as a better and greener approach to synthesise these nanocarriers. It could then be utilised to load drugs and improve their solubility, as seen in the case of domperidone.

A Comparison between the Molecularly Imprinted and Non-Molecularly Imprinted Cyclodextrin-Based Nanosponges for the Transdermal Delivery of Melatonin.

Melatonin is a neurohormone that ameliorates many health conditions when it is administered as a drug, but its drawbacks are its oral and intravenous fast release. To overcome the limitations associated with melatonin release, cyclodextrin-based nanosponges (CD-based NSs) can be used. Under their attractive properties, CD-based NSs are well-known to provide the sustained release of the drug. Green cyclodextrin (CD)-based molecularly imprinted nanosponges (MIP-NSs) are successfully synthesized by reacting β-Cyclodextrin (β-CD) or Methyl-β Cyclodextrin (M-βCD) with citric acid as a cross-linking agent at a 1:8 molar ratio, and melatonin is introduced as a template molecule. In addition, CD-based non-molecularly imprinted nanosponges (NIP-NSs) are synthesized following the same procedure as MIP-NSs without the presence of melatonin. The resulting polymers are characterized by CHNS-O Elemental, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric (TGA), Differential Scanning Calorimetry (DSC), Zeta Potential, and High-Performance Liquid Chromatography (HPLC-UV) analyses, etc. The encapsulation efficiencies are 60-90% for MIP-NSs and 20-40% for NIP-NSs, whereas melatonin loading capacities are 1-1.5% for MIP-NSs and 4-7% for NIP-NSs. A better-controlled drug release performance (pH = 7.4) for 24 h is displayed by the in vitro release study of MIP-NSs (30-50% released melatonin) than NIP-NSs (50-70% released melatonin) due to the different associations within the polymeric structure. Furthermore, a computational study, through the static simulations in the gas phase at a Geometry Frequency Non-covalent interactions (GFN2 level), is performed to support the inclusion complex between βCD and melatonin with the automatic energy exploration performed by Conformer-Rotamer Ensemble Sampling Tool (CREST). A total of 58% of the CD/melatonin interactions are dominated by weak forces. CD-based MIP-NSs and CD-based NIP-NSs are mixed with cream formulations for enhancing and sustaining the melatonin delivery into the skin. The efficiency of cream formulations is determined by stability, spreadability, viscosity, and pH. This development of a new skin formulation, based on an imprinting approach, will be of the utmost importance in future research at improving skin permeation through transdermal delivery, associated with narrow therapeutic windows or low bioavailability of drugs with various health benefits.

Developing New Cyclodextrin-Based Nanosponges Complexes to Improve Vitamin D Absorption in an In Vitro Study

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, βNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The βNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.

Oral supplementation of solvent-free kynurenic acid/cyclodextrin nanosponges complexes increased its bioavailability

Many nutraceuticals present problems due to their poor water solubility or stability, which prevents the final bioactivity achievement. For that reason, the oral administration of KYNA complexed with HPβ-CD and βNS-CDI nanosponges was evaluated in mice. The solvent-free technology was used to prepare the complexes in a complete comparison between kneading in ball milling and classical inclusion complex preparation. The solvent-free ones showed higher strength and efficiency with ball milling, considerably reducing time. A 50 mg KYNA/kg/day dosage was orally administered in formulations showing a higher bioavailability when the nutraceutical was complexed with βNS-CDI compared to HPβ-CD and free KYNA, respectively. Several antioxidant statuses demonstrated a higher global antioxidant level perfectly related to bioavailability. Finally, the formulation of KYNA reduced the temporal oxidative stress damage in the kidney and liver, making βNS-CDI the best formulation. These results suggest an important future application of cyclodextrin-based nanosponges for the oral delivery of nutraceuticals and their stabilization.

Insights on macro- and microscopic interactions between Confidor and cyclodextrin-based nanosponges

Imidacloprid is one of the most widely used soluble neonicotinoid insecticide, which is non–volatile and persists in the soil, with hazardous effects on birds, honeybees, and mammals. It is used in both agricultural and veterinary applications, and is found in at least 7% of European topsoils. One of the commercially available formulations is Confidor O–TEQ® that exhibits higher retention, spreading, and penetration capacity being in form of an oil suspension. In this work, porous materials based on cyclodextrin nanosponges (CDNSs) were developed for the efficient removal of imidacloprid. In the synthesis of CDNSs, α– and β–cyclodextrin and two diamine monomers, hexane–1,6–diamine (HDA) and dodecane–1,12–diamine (DDA) were used. It was found that linkers with longer aliphatic chains resulted in CDNSs with higher thermal stability and crosslinking degree. αCD2–HDA and βCD2–HDA showed superior sorption efficiency for Confidor O–TEQ®, as evaluated by kinetic and equilibrium sorption analyses at optimal conditions. To better understand the effects of monomer chain length and type of cyclodextrin, the sorption performance of αCD and βCD, αCD–HDA and βCD–HDA, αCD–DDA and βCD–DDA, dimeric αCD2–HDA and βCD2–HDA, and αCD2–DDA and βCD2–DDA with imidacloprid was also investigated by atomistic molecular dynamics simulations. Relevant contact patterns based on the identification of the stabilizing/destabilizing noncovalent interactions within the CD-based complexes were described in detail. Results suggest that significant modulation of the sorption performance of CDNSs for imidacloprid can be achieved by imposing various features, with direct implications for the rational design of supramolecular materials with high sorption capacity for pesticides.

Complexing the Marine Sesquiterpene Euplotin C by Means of Cyclodextrin-Based Nanosponges: A Preliminary Investigation.

Euplotin C is a sesquiterpene of marine origin endowed with significant anti-microbial and anti-tumor properties. Despite the promising functional profile, its progress as a novel drug candidate has failed so far, due to its scarce solubility and poor stability in aqueous media, such as biological fluids. Therefore, overcoming these limits is an intriguing challenge for the scientific community. In this work, we synthesized β-cyclodextrin-based nanosponges and investigated their use as colloidal carriers for stably complex euplotin C. Results obtained proved the ability of the carrier to include the natural compound, showing remarkable values of both loading efficiency and capacity. Moreover, it also allowed us to preserve the chemical structure of the loaded compound, which was recovered unaltered once extracted from the complex. Therefore, the use of β-cyclodextrin-based nanosponges represents a viable option to vehiculate euplotin C, thus opening up its possible use as pharmacologically active compound.