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Keywords = cyclodextrin based nanosponges

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34 pages, 5816 KiB  
Article
Adsorption of Bisphenol A onto β-Cyclodextrin–Based Nanosponges and Innovative Supercritical Green Regeneration of the Sustainable Adsorbent
by Uğur Salgın, İsmail Alomari, Nagihan Soyer and Sema Salgın
Polymers 2025, 17(7), 856; https://doi.org/10.3390/polym17070856 - 23 Mar 2025
Viewed by 807
Abstract
Bisphenol A is a widely recognized endocrine disruptor that persists in ecosystems, harms aquatic organisms, and contributes to ecological degradation, raising global environmental concerns. Numerous studies have explored β-cyclodextrin–based adsorbents for Bisphenol A removal; however, their regeneration remains a major challenge, often relying [...] Read more.
Bisphenol A is a widely recognized endocrine disruptor that persists in ecosystems, harms aquatic organisms, and contributes to ecological degradation, raising global environmental concerns. Numerous studies have explored β-cyclodextrin–based adsorbents for Bisphenol A removal; however, their regeneration remains a major challenge, often relying on energy-intensive processes and excessive use of organic solvents. In this study, Bisphenol A was selected as a model pollutant, and its adsorption onto β-cyclodextrin nanosponges was investigated. After adsorption, Bisphenol A was efficiently recovered from the saturated β-cyclodextrin nanosponges using an innovative and sustainable supercritical CO2-based green process, which simultaneously regenerated the adsorbent. The adsorption process achieved an efficiency of 95.51 ± 0.82% under optimized conditions (C0 = 150 mg/L, mβ-CDNS = 0.15 g, T = 25 °C, and N = 200 rpm), with a maximum adsorption capacity of 47.75 ± 0.28 mg/g. The regeneration process achieved over 99% efficiency at 60 °C and 300 bar, with 10% (v/v) ethanol as a co-solvent, nearly fully restoring the adsorbent’s performance. Unlike conventional regeneration techniques, this green approach eliminates the need for environmentally harmful organic solvents while preserving the adsorbent’s structural integrity, making it a highly efficient and sustainable alternative. This study is the first to demonstrate the effective application of supercritical CO2-based regeneration for β-cyclodextrin nanosponges in Bisphenol A removal, providing a scalable and environmentally sustainable solution for wastewater treatment. Furthermore, characterization analyses confirmed that the adsorbent retained its chemical and morphological stability after adsorption and regeneration. Full article
(This article belongs to the Collection Polymer Applications in Environmental Science)
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28 pages, 9610 KiB  
Article
Development and Evaluation of Hydrogel-Based Sulfasalazine-Loaded Nanosponges for Enhanced Topical Psoriasis Therapy
by Sunil Kumar, Anroop B. Nair, Varsha Kadian, Pooja Dalal, Babu Lal Jangir, Bandar Aldhubiab, Rashed M. Almuqbil, Ahmed S. Alnaim, Nouf Alwadei and Rekha Rao
Pharmaceuticals 2025, 18(3), 391; https://doi.org/10.3390/ph18030391 - 10 Mar 2025
Cited by 1 | Viewed by 1173
Abstract
Background: The low solubility and poor skin permeability of sulfasalazine (SLZ) present significant challenges for its effective topical delivery. The objective of the current investigation is to formulate a hydrogel-based SLZ-loaded cyclodextrin nanosponge for topical therapy in psoriasis. Methods: SLZ-loaded nanosponges were prepared [...] Read more.
Background: The low solubility and poor skin permeability of sulfasalazine (SLZ) present significant challenges for its effective topical delivery. The objective of the current investigation is to formulate a hydrogel-based SLZ-loaded cyclodextrin nanosponge for topical therapy in psoriasis. Methods: SLZ-loaded nanosponges were prepared by the melt polymerization method and evaluated for physiochemical characteristics, drug release, and cytocompatibility. The selected nanosponges (SLZ-NS4) were transformed to hydrogel and further evaluated for rheology, texture, safety, skin permeability, and in vivo for anti-psoriatic effect in mouse tail and imiquimod-induced psoriasis-like inflammation models in mice. Results: Physiochemical data confirms nanoscale architecture, drug inclusion in nanosponges, crystalline structure, and formulation stability. The release profile of SLZ-NS4 revealed sustained release behavior (22.98 ± 2.24% in 3 h). Cytotoxicity assays indicated negligible toxicity against THP1 cells, resulting in higher viability of cells than pure SLZ (p < 0.05). The HET-CAM assay confirmed the safety, while confocal laser scanning microscopy demonstrated deeper skin permeation of SLZ. In the mouse tail model, a remarkable decline in relative epidermal thickness, potential improvement in percent orthokeratosis, and drug activity with respect to control was observed in animals treated with SLZ-NS4 hydrogel. The efficiency of the developed SLZ-NS4-loaded hydrogel in treating psoriasis was confirmed by the decline in PASI score (81.68 ± 3.61 and 84.86 ± 5.74 with 1 and 2% w/v of SLZ-NS-HG). Histopathological analysis and assessment of oxidative stress markers revealed the profound anti-psoriatic potential of the fabricated SLZ-NS4 hydrogel. Conclusions: These findings highlight the profound potential of the developed delivery system as an effective topical therapy for psoriasis. Full article
(This article belongs to the Special Issue Progress of Hydrogel Applications in Novel Drug Delivery Platforms)
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23 pages, 8373 KiB  
Article
Cyclodextrin-Nanosponge-Loaded Cyclo-Oxygenase-2 Inhibitor-Based Topical Gel for Treatment of Psoriatic Arthritis: Formulation Design, Development, and In vitro Evaluations
by Umme Hani, Sharanya Paramshetti, Mohit Angolkar, Wajan Khalid Alqathanin, Reema Saeed Alghaseb, Saja Mohammed Al Asmari, Alhanouf A. Alsaab, Farhat Fatima, Riyaz Ali M. Osmani and Ravi Gundawar
Pharmaceuticals 2024, 17(12), 1598; https://doi.org/10.3390/ph17121598 - 27 Nov 2024
Cited by 3 | Viewed by 1674
Abstract
Background: Psoriatic arthritis (PsA), a chronic inflammatory disease, mainly affects the joints, with approximately 30% of psoriasis patients eventually developing PsA. Characterized by both innate and adaptive immune responses, PsA poses significant challenges for effective treatment. Recent advances in drug delivery systems have [...] Read more.
Background: Psoriatic arthritis (PsA), a chronic inflammatory disease, mainly affects the joints, with approximately 30% of psoriasis patients eventually developing PsA. Characterized by both innate and adaptive immune responses, PsA poses significant challenges for effective treatment. Recent advances in drug delivery systems have sparked interest in developing novel formulations to improve therapeutic outcomes. The current research focuses on the development and evaluation of a nanosponge-loaded, cyclo-oxygenase-2 (COX-2) inhibitor-based topical gel for the treatment of PsA. Methods: Nanosponges (NSs) were prepared by using beta-cyclodextrin as a polymer and dimethyl carbonate (DMC) as a crosslinker by melting, and gels were prepared by employing carbopol and badam gum as polymers. Results: Solubility studies confirmed that the prepared nanosponges were highly soluble. FT-IR studies confirmed the formation of hydrogen bonds between lumiracoxib and beta-cyclodextrin. SEM confirmed that the prepared formulations were roughly spherical and porous in nature. The average particle size was 190.5 ± 0.02 nm, with a zeta potential of −18.9 mv. XRD studies showed that the crystallinity of lumiracoxib decreased after encapsulation, which helped to increase its solubility. The optimized nanosponges (NS2) were incorporated in an optimized gel (FG10) to formulate a nanosponge-loaded topical gel. The optimized gel formulation exhibited a homogeneous consistency, with a pH of 6.8 and a viscosity of 1.15 PaS, indicating its suitability for topical application and stability. The in vitro diffusion studies for the topical gel showed drug release of 82.32% in 24 h. The optimized formulation demonstrated significant antipsoriatic activity, as confirmed through cytotoxicity studies conducted on HaCaT cells. Conclusions: On the basis of the findings, it can be concluded that the prepared nanosponge-loaded topical gel formulation presents a promising solution for the effective management of PsA, offering enhanced drug solubility, sustained release, and improved therapeutic potential. Full article
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17 pages, 571 KiB  
Review
Advances in Cyclodextrins and Their Derivatives in Nano-Delivery Systems
by Xin-Yu Ji, Yi-Xuan Zou, Han-Fang Lei, Yong Bi, Rui Yang, Ji-Hui Tang and Qing-Ri Jin
Pharmaceutics 2024, 16(8), 1054; https://doi.org/10.3390/pharmaceutics16081054 - 9 Aug 2024
Cited by 9 | Viewed by 2147
Abstract
The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of [...] Read more.
The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of applications of cyclodextrins and their derivatives in nano-delivery systems. The areas covered include nanospheres, nano-sponges, nanogels, cyclodextrin metal–organic frameworks, liposomes, and emulsions, providing a comprehensive and in-depth understanding of the design and development of nano-delivery systems. Full article
(This article belongs to the Special Issue Cyclodextrins and Associated Nanomaterials for Drug and Gene Delivery)
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16 pages, 4054 KiB  
Article
Investigating the Effect of Cyclodextrin Nanosponges and Cyclodextrin-Based Hydrophilic Polymers on the Chemical Pharmaceutical and Toxicological Profile of Al(III) and Ga(III) Complexes with 5-Hydroxyflavone
by Claudiu Radu, Andreea Alexandra Olteanu, Corina Cristina Aramă, Mirela Mihăilă and Valentina Uivaroși
Appl. Sci. 2024, 14(13), 5441; https://doi.org/10.3390/app14135441 - 23 Jun 2024
Viewed by 1447
Abstract
In the present study, the complexes of aluminum and gallium with 5-hydroxyflavone were evaluated for their interaction with cyclodextrin polymers, as well as for the pharmacological effect of their inclusion. The cyclodextrin polymers were synthesized using diphenylcarbonate as a crosslinking agent, resulting in [...] Read more.
In the present study, the complexes of aluminum and gallium with 5-hydroxyflavone were evaluated for their interaction with cyclodextrin polymers, as well as for the pharmacological effect of their inclusion. The cyclodextrin polymers were synthesized using diphenylcarbonate as a crosslinking agent, resulting in a lipophilic nanosponge (DPCNS), and pyromellitic dianhydride, resulting in a hydrophilic polymer (PMDACD). The inclusion complexes were synthesized and characterized via IR spectrometry and thermal analysis. The effect on the solubility of the metal complexes was also studied, where the hydrophobic nanosponge did not lead to an increase in solubility, but on the contrary, in the case of Al, it decreased; meanwhile, in the case of the hydrophilic polymer, the solubility of the metal complexes increased with the amount of polymer added. The cytostatic effect of inclusion complexes was investigated on two cell lines with different localizations, human colon adenocarcinoma (LoVo) and human ovarian adenocarcinoma (SKOV-3). The cytostatic efficacy is increased compared to simple complexes with efficacy on LoVo cells. Compared between the two metals, gallium complexes proved to be more active, with the efficacy of gallium complexes with the PMDACD being approximately the same as that of cisplatin, an antitumor agent used in therapy. Full article
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19 pages, 4414 KiB  
Article
Composite RGO/Ag/Nanosponge Materials for the Photodegradation of Emerging Pollutants from Wastewaters
by Ettore Madonia, Antonella Di Vincenzo, Alberto Pettignano, Roberto Scaffaro, Emmanuel Fortunato Gulino, Pellegrino Conte and Paolo Lo Meo
Materials 2024, 17(10), 2319; https://doi.org/10.3390/ma17102319 - 14 May 2024
Cited by 2 | Viewed by 3782
Abstract
Some composite materials have been prepared, constituted by a cyclodextrin-bis-urethane-based nanosponge matrix in which a reduced graphene oxide/silver nanoparticles photocatalyst has been dispersed. Different chain extenders were employed for designing the nanosponge supports, in such a way as to decorate their [...] Read more.
Some composite materials have been prepared, constituted by a cyclodextrin-bis-urethane-based nanosponge matrix in which a reduced graphene oxide/silver nanoparticles photocatalyst has been dispersed. Different chain extenders were employed for designing the nanosponge supports, in such a way as to decorate their hyper-cross-linked structure with diverse functionalities. Moreover, two different strategies were explored to accomplish the silver loading. The obtained systems were successfully tested as catalysts for the photodegradation of emerging pollutants such as model dyes and drugs. Enhancement of the photoactive species performance (up to nine times), due to the synergistic local concentration effect exerted by the nanosponge, could be assessed. Overall, the best performances were shown by polyamine-decorated materials, which were able to promote the degradation of some particularly resistant drugs. Some methodological issues pertaining to data collection are also addressed. Full article
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50 pages, 4315 KiB  
Review
Exploring Cyclodextrin-Based Nanosponges as Drug Delivery Systems: Understanding the Physicochemical Factors Influencing Drug Loading and Release Kinetics
by Bartłomiej Pyrak, Karolina Rogacka-Pyrak, Tomasz Gubica and Łukasz Szeleszczuk
Int. J. Mol. Sci. 2024, 25(6), 3527; https://doi.org/10.3390/ijms25063527 - 20 Mar 2024
Cited by 23 | Viewed by 3239
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Cyclodextrin-Based Polymer Systems for Biomedical Applications)
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26 pages, 3577 KiB  
Article
Enhancing Vitamin D3 Efficacy: Insights from Complexation with Cyclodextrin Nanosponges and Its Impact on Gut–Brain Axes in Physiology and IBS Syndrome
by Francesca Uberti, Francesco Trotta, Roberta Cavalli, Rebecca Galla, Fabrizio Caldera, Sara Ferrari, Simone Mulè, Arianna Brovero, Claudio Molinari, Pasquale Pagliaro and Claudia Penna
Int. J. Mol. Sci. 2024, 25(4), 2189; https://doi.org/10.3390/ijms25042189 - 11 Feb 2024
Cited by 6 | Viewed by 2311
Abstract
Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin [...] Read more.
Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin (βNS-CDI 1:4) nanosponges (NS) (defined as VitD3NS). Therefore, its activity has been evaluated on two different gut–brain axes (healthy gut/degenerative brain and inflammatory bowel syndrome gut/degenerative brain axis). At the gut level, VitD3-NS mitigated liposaccharide-induced damage (100 ng/mL; for 48 h), restoring viability, integrity, and activity of tight junctions and reducing ROS production, lipid peroxidation, and cytokines levels. Following intestinal transit, VitD3-NS improved the neurodegenerative condition in the healthy axis and the IBS model, suggesting the ability of VitD3-NS to preserve efficacy and beneficial effects even in IBS conditions. In conclusion, this study demonstrates the ability of this novel form of VitD3, named VitD3-NS, to act on the gut–brain axis in healthy and damaged conditions, emphasizing enhanced biological activity through VitD3 complexation, as such complexation increases the beneficial effect of vitamin D3 in both the gut and brain by about 50%. Full article
(This article belongs to the Special Issue Cyclodextrins: Properties and Applications, 2nd Edition)
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53 pages, 8211 KiB  
Review
Cyclodextrin Inclusion Complexes for Improved Drug Bioavailability and Activity: Synthetic and Analytical Aspects
by Álvaro Sarabia-Vallejo, María del Mar Caja, Ana I. Olives, M. Antonia Martín and J. Carlos Menéndez
Pharmaceutics 2023, 15(9), 2345; https://doi.org/10.3390/pharmaceutics15092345 - 19 Sep 2023
Cited by 93 | Viewed by 9934
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Development of Chitosan/Cyclodextrins in Drug Delivery Field)
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17 pages, 2848 KiB  
Article
Oxygen Nanocarriers for Improving Cardioplegic Solution Performance: Physico-Chemical Characterization
by Maria Tannous, Gjylije Hoti, Francesco Trotta, Roberta Cavalli, Takanobu Higashiyama, Pasquale Pagliaro and Claudia Penna
Int. J. Mol. Sci. 2023, 24(12), 10073; https://doi.org/10.3390/ijms241210073 - 13 Jun 2023
Cited by 3 | Viewed by 1639
Abstract
Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, [...] Read more.
Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure. Full article
(This article belongs to the Special Issue Multifunctional Application of Biopolymers and Biomaterials)
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21 pages, 7149 KiB  
Article
β-Cyclodextrin Nanosponges Inclusion Compounds Associated with Silver Nanoparticles to Increase the Antimicrobial Activity of Quercetin
by Sebastián Salazar Sandoval, Tamara Bruna, Francisca Maldonado-Bravo, Karen Bolaños, Sofía Adasme-Reyes, Ana Riveros, Nelson Caro, Nicolás Yutronic, Nataly Silva, Marcelo J. Kogan and Paul Jara
Materials 2023, 16(9), 3538; https://doi.org/10.3390/ma16093538 - 5 May 2023
Cited by 7 | Viewed by 3033
Abstract
This work aimed to synthesize and characterize a nanocarrier that consisted of a ternary system, namely β-cyclodextrin-based nanosponge (NS) inclusion compounds (ICs) associated with silver nanoparticles (AgNPs) to increase the antimicrobial activity of quercetin (QRC). The nanosystem was developed to overcome the therapeutical [...] Read more.
This work aimed to synthesize and characterize a nanocarrier that consisted of a ternary system, namely β-cyclodextrin-based nanosponge (NS) inclusion compounds (ICs) associated with silver nanoparticles (AgNPs) to increase the antimicrobial activity of quercetin (QRC). The nanosystem was developed to overcome the therapeutical limitations of QRC. The host–guest interaction between NSs and QRC was confirmed by field emission scanning electron microscopy (FE–SEM), X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), and proton nuclear magnetic resonance (1H–NMR). Moreover, the association of AgNPs with the NS–QRC was characterized using FE–SEM, energy-dispersive spectroscopy (EDS), transmission electron microscopy (TEM), dynamic light scattering (DLS), ζ-potential, and UV–Vis. Finally, the antimicrobial activity of the novel formulations was tested, which depicted that the complexation of QRC inside the supramolecular interstices of NSs increases the inhibitory effects against Escherichia coli ATCC25922, as compared to that observed in the free QRC. In addition, at the same concentrations used to generate an antibacterial effect, the NS–QRC system with AgNPs does not affect the metabolic activity of GES–1 cells. Therefore, these results suggest that the use of NSs associated with AgNPs resulted in an efficient strategy to improve the physicochemical features of QRC. Full article
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17 pages, 4654 KiB  
Article
Optimisation of a Greener-Approach for the Synthesis of Cyclodextrin-Based Nanosponges for the Solubility Enhancement of Domperidone, a BCS Class II Drug
by Mohit Vij, Neha Dand, Lalit Kumar, Pankaj Wadhwa, Shahid Ud Din Wani, Wael A. Mahdi, Sultan Alshehri, Prawez Alam and Faiyaz Shakeel
Pharmaceuticals 2023, 16(4), 567; https://doi.org/10.3390/ph16040567 - 10 Apr 2023
Cited by 10 | Viewed by 3093
Abstract
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 [...] Read more.
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. Full article
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27 pages, 8779 KiB  
Article
A Comparison between the Molecularly Imprinted and Non-Molecularly Imprinted Cyclodextrin-Based Nanosponges for the Transdermal Delivery of Melatonin
by Gjylije Hoti, Riccardo Ferrero, Fabrizio Caldera, Francesco Trotta, Marta Corno, Stefano Pantaleone, Mohamed M. H. Desoky and Valentina Brunella
Polymers 2023, 15(6), 1543; https://doi.org/10.3390/polym15061543 - 20 Mar 2023
Cited by 15 | Viewed by 3452
Abstract
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 [...] Read more.
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. Full article
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15 pages, 2087 KiB  
Article
Developing New Cyclodextrin-Based Nanosponges Complexes to Improve Vitamin D Absorption in an In Vitro Study
by Francesca Uberti, Francesco Trotta, Pasquale Pagliaro, Daniel Mihai Bisericaru, Roberta Cavalli, Sara Ferrari, Claudia Penna and Adrián Matencio
Int. J. Mol. Sci. 2023, 24(6), 5322; https://doi.org/10.3390/ijms24065322 - 10 Mar 2023
Cited by 15 | Viewed by 2431
Abstract
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. [...] Read more.
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. Full article
(This article belongs to the Collection State-of-the-Art Materials Science in Italy)
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15 pages, 7515 KiB  
Article
Preparation and Evaluation of Diosmin-Loaded Diphenylcarbonate-Cross-Linked Cyclodextrin Nanosponges for Breast Cancer Therapy
by Md. Khalid Anwer, Mohammed Muqtader Ahmed, Mohammed F. Aldawsari, Muzaffar Iqbal and Vinay Kumar
Pharmaceuticals 2023, 16(1), 19; https://doi.org/10.3390/ph16010019 - 23 Dec 2022
Cited by 17 | Viewed by 3324
Abstract
In the current study, diosmin (DSM)-loaded beta-cyclodextrin (β-CD)-based nanosponges (NSPs) using diphenylcarbonate (DPC) as a cross-linker were prepared. Four different DSM-loaded NSPs (D-NSP1-NSP4) were developed by varying the molar ratio of β-CD: DCP (1:15–1:6). Based on preliminary evaluations, NSPs (D-NSP3) were optimized for [...] Read more.
In the current study, diosmin (DSM)-loaded beta-cyclodextrin (β-CD)-based nanosponges (NSPs) using diphenylcarbonate (DPC) as a cross-linker were prepared. Four different DSM-loaded NSPs (D-NSP1-NSP4) were developed by varying the molar ratio of β-CD: DCP (1:15–1:6). Based on preliminary evaluations, NSPs (D-NSP3) were optimized for size (412 ± 6.1 nm), polydispersity index (PDI) (0.259), zeta potential (ZP) (−10.8 ± 4.3 mV), and drug loading (DL) (88.7 ± 8.5%), and were further evaluated by in vitro release, scanning electron microscopy (SEM), and in vitro antioxidant studies. The NSPs (D-NSP3) exhibited improved free radical scavenging activity (85.58% at 100 g/mL) compared to pure DSM. Dissolution efficiency (%DE) was enhanced to 71.50% (D-NSP3) from plain DSM (58.59%). The D-NSP3 formulation followed the Korsmeyer–Peppas kinetic model and had an n value of 0.529 indicating a non-Fickian and controlled release by diffusion and relaxation. The D-NSP3 showed cytotoxic activity against MCF-7 breast cancer, as evidenced by caspase 3, 9, and p53 activities. According to the findings, DSM-loaded NSPs might be a promising therapy option for breast cancer. Full article
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