Search Results (211)

Background/Objectives: Intracellular delivery of RNA molecules is challenging. To solve this problem, many carrier systems are available, which are based on liposomes or polymers. Cyclodextrins are widely used excipients to increase the solubility of small molecules, but their polymer derivatives are able to deliver macromolecules. In the present study, we aimed to investigate and compare the siRNA and mRNA carrying capacity of a cationic quaternary ammonium β-cyclodextrin polymer (QABCDPS) and polyethylenimine (PEI). Methods: Cytotoxicity of the polymers was tested by the MTT method. Polyplexes were formulated with different nitrogen/phosphate ratios (NP), and their physicochemical properties were examined using dynamic light scattering and zeta potential measurements. Cellular internalization and intracellular effects of the polyplexes were investigated by confocal microscopy and flow cytometry. Results: QABCDPS exhibited lower toxicity compared to PEI, effectively binding both siRNA and mRNA and delivering them into vesicles in the cytoplasm, but showing different internalization patterns. Polyplexes formed with PEI showed stronger biological effect than those with QABCDPS, which can be attributed to the strength of interactions facilitated by the polymers. Conclusions: In summary, QABCDPS is a low-toxicity carrier that shows some promise for mRNA delivery but is ineffective for siRNA silencing under the tested conditions and requires further structural optimization. Full article

Flunarizine is a calcium channel blocker widely used in neurological disorders; however, its low aqueous solubility may influence formulation stability and drug dispersion in polymer-based systems. The present study aimed to evaluate the compatibility of flunarizine with selected excipients and to investigate its incorporation into polymeric hydrogel matrices. Binary mixtures of flunarizine with excipients such as hydroxypropyl-β-cyclodextrin, polyethylene glycol (PEG 6000), Tween 20, gelatin, and citric acid were prepared and characterized using Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG/DTG), and high-performance liquid chromatography (HPLC). The FTIR spectra of the analyzed samples do not reveal the appearance of new absorption bands that may indicate chemical interactions; instead, minor spectral variations were observed due to weak intermolecular interactions within the polymer network. Thermal analysis revealed decomposition patterns consistent with those of the individual components, suggesting the absence of significant incompatibilities. A validated RP-HPLC method enabled sensitive and reliable quantification of flunarizine in the analyzed systems, with a limit of detection (LOD) of 0.05 µg/mL and a limit of quantitation (LOQ) of 0.16 µg/mL. Accuracy testing showed average recovery rates of 100% across 80–120% spiking levels. Overall, the results support the compatibility of flunarizine with the investigated excipients and the suitability of the studied hydrogels as potential drug delivery matrices. Full article

Hybrid supramolecular–nanocomposite hydrogels based on polyethylene glycol (PEG), β-cyclodextrin–adamantane host–guest interactions, and silica nanoparticles represent an important class of hierarchical soft materials with tunable viscoelastic and transport properties. This review critically analyzes recent progress in cyclodextrin–silica hybrid PEG hydrogels, focusing on the mechanistic coupling between stiffness, stress relaxation, and molecular transport arising from the interplay between reversible supramolecular crosslinks and nanoparticle-induced confinement effects. Particular attention is given to how host–guest exchange kinetics regulate dynamic bond rearrangement and affinity-mediated retention of hydrophobic cargo, while silica nanoparticles enhance mechanical reinforcement and modify diffusion pathways through tortuosity and interfacial polymer–particle interactions. The analysis highlights how nanoparticle size, loading level, and surface functionalization influence relaxation spectra and network topology, as well as how environmental stimuli may affect supramolecular bond stability and overall material performance. Comparison with alternative inorganic fillers and mesoporous silica architectures further clarifies the specific advantages of silica in achieving balanced mechanical stability and controlled transport behavior. Overall, current evidence indicates that hybrid CD–silica networks enable partial decoupling of stiffness, relaxation dynamics, and diffusion, although complete independence remains constrained by fundamental polymer physics relationships. These insights support the development of predictive structure–property frameworks for advanced biomedical and controlled release applications. Full article

Background/Objectives: Inclusion complexes among drugs and cyclodextrin-modified polymers are a topic of recent interest in pharmaceutical research and industry as they might expand the solubility, bioavailability, and stability of the guest molecules. Polyurethanes derived from cyclodextrins show some biomedical applications. In this study, two cross-linked polyurethane networks based on hydroxypropyl-β-cyclodextrin (HPβCD) and polyethylene glycols (PEG 2000 or PEG 6000) were synthesized with NCO/OH molar ratio 4.3 and 6.3 by the typical two-step polymerization method. Methods: Inclusion complexes of clotrimazole (CLOT) with two HPβCD-modified polyurethane networks and their corresponding physical mixtures were prepared using kneading methods and physical mixing in a 1:6 weight ratio of CLOT:HPβCD. Results: Obtained prepolymers, previously end-capped with isocyanate groups forming urethane links with HPβCD, which were confirmed by FTIR analysis. TGA results indicate a slight increase in thermal stability of the prepared complexes. The characteristic endothermic peak of the CLOT at around 145.90 °C did not appear in the DSC curve of the drug-loaded inclusion complexes. The XRD patterns of physical mixtures showed specific peaks corresponding to pure clotrimazole. SEM micrographs confirmed an elliptical/spherical- and plate-shaped particles without phase segregation, indirectly confirming that CLOT is not separately present due to inclusion into HPβCD and entrapment into polyurethane networks. Novel complexes PUR2/HPβCD-CLOT-IC and PUR3/HPβCD-CLOT-IC were applied as drug carriers, and diffusion-controlled kinetics of CLOT release were best described using Higuchi model. Conclusions: The obtained in vitro results showed surprisingly slow/prolonged clotrimazole release from modified polyurethane networks due to the significant influence of NCO/OH molar ratio and the chosen polyol soft segments chain length with potential in vivo applications. Full article

This study assesses the stability, in vitro bioaccessibility and potential bioavailability, and in vivo genotoxicity and toxicity of polyethylene glycol–soy lecithin (PEGSL-ACG-NSps) or β-cyclodextrin–soy lecithin (βCDSL-ACG-NSps) nanosuspensions (NSps). Both formulations exhibited initial particle sizes below 130 nm and PDI values below 0.3. Under simulated gastrointestinal conditions, PEGSL-ACG-NSps preserved structural integrity, with only a moderate size increase (~239 nm) in the intestinal phase and controlled release of acetogenins (ACGs); in contrast, βCDSL-ACG-NSps destabilized considerably (size > 500 nm) and released ACGs rapidly. Consistently, βCDSL-ACG-NSps achieved higher in vitro bioaccessibility and a potential bioavailability (up to 95% from post-digestion recovery). In contrast, PEGSL-ACG-NSps displayed a more gradual release profile (up to 55%). In vivo toxicity tests in mice showed no significant genotoxic or cytotoxic effects for either formulation, even at high doses. These findings suggest that selecting appropriate food-grade stabilizing polymers is crucial for optimizing NSps for the oral delivery of ACGs as therapeutic agents. Full article

Background: Menopause is characterised by a decline in oestrogen levels, leading to physical and psychological symptoms that significantly affect quality of life. Current parenteral oestradiol ester therapies, while effective, are often associated with side effects due to their oil-based formulations, including injection-site reactions and immune responses. Methods: In this study, we developed a water-soluble, polyethylene glycol cross-linked β-cyclodextrin (PEG–β-CD) polymer-based system for parenteral oestradiol delivery and evaluated its biocompatibility, solubility enhancement, immune compatibility, and pharmacokinetics. Results: Cytotoxicity assays using NIH-3T3 fibroblasts and RAW 264.7 macrophages showed minimal toxicity up to 10% (w/w). Phase-solubility studies demonstrated a significant increase in oestradiol solubility with the PEG–β-CD polymer, surpassing that of β-cyclodextrin or PEG alone. Dynamic light scattering and FTIR analyses confirmed successful complex formation, with submicron particles averaging 271 nm and physical incorporation of oestradiol into the polymer matrix. Macrophage activation assays and RT-qPCR analyses indicated an absence of immunogenic responses or pro-inflammatory cytokine induction. In vivo toxicity testing in Galleria mellonella larvae confirmed safety, while pharmacokinetic studies in Wistar rats revealed rapid initial absorption followed by stable, low-level serum concentrations comparable to those of commercially used oestradiol esters. Conclusions: These findings indicate that the PEG–β-CD polymer–oestradiol complex provides a safe, water-based alternative to traditional oil-based injections, with the potential to reduce side effects and improve patient compliance in postmenopausal hormone therapy. Full article

Background: Oral insulin improves compliance and convenience in patients with diabetes who require regular needle injections. However, the clinical application of oral insulin preparations has been limited due to instability and inefficient permeation through the gastrointestinal tract. In this study, a novel cationic polysaccharide nanodrug delivery platform was designed for efficient oral insulin delivery. Methods: The innovative thiolated trimethyl chitosan-grafted β-cyclodextrin (NCT) was synthesized by utilizing N-trimethyl chitosan (TMC) as the polymer backbone. This involved modifying TMC with thiol group-containing N-acetylcysteine and carboxymethyl-β-cyclodextrin that possesses hydrophobic cavities via an amide condensation reaction. Subsequently, this polymer was employed to construct the NCT nanoparticle system using an ionic cross-linking method. The physicochemical properties of the NCT nanoparticles were systematically analyzed, and their therapeutic efficacy was comprehensively evaluated in streptozotocin (STZ)-induced animal models. Results: The NCT nanoparticles demonstrated mucus adhesion, permeability, and pH sensitivity, which facilitated a slow and controlled release within the gastrointestinal microenvironment due to both ionic electrostatic interactions and disulfide bonding interactions. The experiments revealed in vivo that insulin/NCT nanoparticles extended the retention time of insulin in the small intestine. Blood glucose levels decreased to approximately 39% of the initial level at 5 h post-administration while exhibiting smooth hypoglycemic efficacy. Simultaneously, insulin bioavailability increased to 12.58%. Conclusions: The NCT nanoparticles effectively protect insulin from degradation in the gastrointestinal microenvironment while overcoming intestinal barriers, thereby providing a promising approach to oral biomolecule delivery. Full article

Water-soluble poly-β-cyclodextrins (PCDs), crosslinked with ethylenediaminetetraacetic acid dianhydride (EDTADA), were synthesized at varying β-CD:EDTADA molar ratios (1:6, 1:9, 1:12, 1:15) to develop multifunctional nanocarriers with the ability to complex drugs, polymers, and ions. All PCDs exhibited nanometric particle sizes (14 to 28 nm), negative zeta potential (−18 to −27 mV), and adjustable content of free carboxyl groups controlled by crosslinker ratio. Functional evaluations demonstrated effective Ca²⁺ chelation and a linear inclusion complexation profile with acyclovir, but not with naproxen, highlighting pH-dependent solubility effects. Additionally, PCDs successfully formed polyelectrolyte complexes with poly-L-lysine, indicating their potential as components of advanced drug delivery systems. Among the analyzed variants, PCD 1:6 showed reduced yields, fewer reactive groups, and diminished ion-binding capacity compared to formulations with higher crosslinker content. These findings underscore the importance of crosslinking density in modulating physicochemical and functional properties and support the potential of EDTA-crosslinked PCDs as versatile platforms for advanced, ion-sensitive biomedical applications. Full article

The contamination of water bodies by polycyclic aromatic hydrocarbons (PAHs) poses a significant concern for the ecological systems, along with public health. Magnetic adsorption stands out as a green and practical solution for treating polluted water. To make the process more efficient and economical, it is important to create materials that not only absorb contaminants effectively but also allow for easy recovery and reuse. This study proposes a simple yet effective method for coating Fe₃O₄ nanoparticles with hydroxypropyl-β-cyclodextrin polymer (HP-β-CDCP). The physicochemical properties of the synthesized sorbent were characterized using a transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and Vibrating Sample Magnetometer (VSM) analysis. The adsorption performance of HP-β-CDCP/Fe₃O₄ nanoparticles was well-described by the pseudo-second-order kinetic model, thermodynamic analysis, and the Freundlich isotherm model, indicating multiple interaction mechanisms with PAHs, such as π–π interactions, hydrogen bonding, and van der Waals forces. Using HP-β-CDCP/Fe₃O₄ nanoparticles as the adsorbent, the purification rates for the fifteen representative PAHs were achieved within the range of 33.9–93.1%, compared to 15.3–64.8% of the unmodified Fe₃O₄ nanoparticles. The adsorption of all studied PAHs onto HP-β-CDCP/Fe₃O₄ nanocomposites was governed by pH, time, and temperature. Equilibrium in the uptake mechanism was obtained within 15 min, with the largest adsorption capacities for PAHs in competitive adsorption mode being 6.46–19.0 mg·g⁻¹ at 20 °C, pH 7.0. This study points to the practical value of incorporating cyclodextrins into tailored polymer frameworks for improving the removal of PAHs from polluted water. Full article

Background/Objectives: Citrus × paradisi Macfad., Rutaceae. peel is a rich source of naringin (NR), but its poor solubility and low bioavailability limit applications. This study aimed to improve NR delivery by comparing microencapsulation, liposomal microencapsulation, and buccal films containing either pure NR or grapefruit peel extract. Methods: Four spray-dried powder formulations—spray-dried NR (NS), liposomal NR (NLS), spray-dried extract (ES), and liposomal extract (ELS)—were produced using maltodextrin, β-cyclodextrin, and HPMC as wall materials. Buccal films (EP1, EP2, NP1, NP2) were prepared via solvent casting with HPMC, alginate (ALG), or polyvinyl alcohol (PVA). All samples were evaluated for solubility, moisture content, mucoadhesion, and in vitro release under simulated gastric, intestinal, and salivary conditions. Results: NR powders had the highest absolute solubility (306.42 ± 10.34 µg/mL), whereas ELS showed the lowest due to low loading. However, relative to theoretical NR content, ELS achieved the highest dissolution efficiency (55.3%), followed by NLS (42.7%), outperforming NS (5.6%) and ES (91.8%) in sustained release potential. Dual encapsulation (NLS, ELS) slowed gastric release and maintained intestinal delivery, while non-liposomal powders released rapidly. In buccal films, NP2 (NR + PVA) showed the highest release (69.97 ± 3.01 µg/mL; 40.9% efficiency) and strongest mucoadhesion (0.47 N·s). Extract-based films had lower absolute NR release but higher relative efficiency to content, likely due to co-extracted compounds enhancing wettability and matrix erosion. Conclusions: Liposomal microencapsulation improves relative dissolution efficiency and sustains intestinal release, while PVA-based buccal films enhance both release and mucoadhesion. Polymer choice and active ingredient composition are critical for optimising oral delivery of NR. These results demonstrate the potential of the proposed systems in the pharmaceutical or dietary supplement field, especially in improving the oral delivery of poorly soluble flavonoids. A graphical summary is included, visually summarising the main formulation strategies and results. Full article

Methicillin-resistant S. aureus is a problematic pathogen due to its high-risk infections and resistance mechanisms. To fight against this bacterium, novel antimicrobial sources and new delivery systems must be developed. Antimicrobial polyurethanes for developing biomaterials can function as preventive strategies. In this study, we explore the synthesis of partially renewable polyurethanes as biomaterial carriers of novel antimicrobials. An antibacterial extract from a Streptomyces sp. strain and its inclusion complexes with β-cyclodextrin, used as an additional protective approach, were incorporated into castor oil-based polyurethane films through bulk or surface loading. The inclusion complexes were characterized to confirm host–guest interactions. The films were characterized by FTIR, XRD spectra, surface SEM images, hydrophilicity, thermal stability, and mechanical performance. FTIR suggested successful polyurethane synthesis. The polymers were semicrystalline and thermally stable until 260 °C, and Tg ranged between −16.9 and −9 °C. Bulk modification decreased the mechanical performance of the films. Surface modification promoted good antibacterial performance but cytotoxic potential against HDFa cells. However, PU active films showed favorable properties and hemocompatibility, making them a promising alternative for applications such as short-term dressings, serving as an antimicrobial delivery system and a preventive strategy against methicillin-resistant S. aureus. Full article

This study aimed to develop and characterise novel hydrogels based on natural bioactive compounds for topical antimicrobial applications. Four gel systems were formulated using different polymers, namely polyacrylic acid (Carbopol 940, CBP-G), chitosan with high and medium molecular weights (CTH-G and CTM-G), and sodium alginate (ALG-G), incorporating tinctures of Verbena officinalis and Aloysia triphylla, Laurus nobilis essential oil, and a β-cyclodextrin–clove essential oil complex. All gels displayed a homogeneous macroscopic appearance and maintained stability for over 90 days. Rheological studies demonstrated gel-like behaviour for CBP-G and ALG-G, with well-defined linear viscoelastic regions and distinct yield points, while CTM-G exhibited viscoelastic liquid-like properties. SEM imaging confirmed uniform and continuous matrices, supporting controlled active compound distribution. Thermogravimetric analysis (TG-DTA) revealed a two-step degradation profile for all gels, characterised by high thermal stability up to 230 °C and near-total decomposition by 500 °C. FTIR spectra confirmed the incorporation of bioactive compounds and products and highlighted varying interaction strengths with polymer matrices, which were stronger in CBP-G and CTH-G. Antimicrobial evaluation demonstrated that chitosan-based gels exhibited the most potent inhibitory and antibiofilm effects (MIC = 2.34 mg/mL) and a cytocompatibility assessment on HaCaT keratinocytes showed enhanced cell viability for chitosan gels and dose-dependent cytotoxicity for alginate formulations at high concentrations. Overall, chitosan-based gels displayed the most favourable combination of stability, antimicrobial activity, and biocompatibility, suggesting their potential for topical pharmaceutical use. Full article

Nepafenac is an anti-inflammatory drug used in ophthalmology, marketed as a suspension due to its low aqueous solubility. A solution formulation could provide better bioavailability than suspension and facilitate single unit doses, avoiding the use of preservatives which are required to maintain sterility in multidose packaging. In this study, solubilization of nepafenac was achieved in the presence of randomly methylated β-cyclodextrin (RAMEB) and the actual complexation was assessed by NMR and phase-solubility studies. It was also found that the addition of hydrophilic polymers plays an important role in allowing increased solubilization of nepafenac at the same cyclodextrin concentration. Compared to complexes of nepafenac with other cyclodextrins, only 5% RAMEB was sufficient to solubilize 0.3% (w/v) nepafenac, enabling for the first time the development of an ophthalmic solution that proved chemically and physically stable for 12 months at 25 °C. The formulated solutions of nepafenac were tested for cytotoxicity on human corneal epithelial cells (HCE-2) and the results suggest their potential as a valuable and safe alternative to the commercially available 0.3% (w/v) suspension of the drug. Full article

This work represents the first use of a phosphonium salt-functionalized β-Cyclodextrin polymer (β-CDP) as a highly selective sensing membrane for monitoring the safety of drinking water against perchlorate ions (ClO₄⁻) using electrochemical impedance spectroscopy (EIS). Structural confirmation via ¹H NMR, ¹³C NMR, ³¹P NMR, and FT-IR spectroscopies combined with AFM and contact angle measurements demonstrate how the enhanced solubility of modified cyclodextrin improves thin film quality. The innovation lies in the synergistic combination of two detection mechanisms: the “Host-Guest” inclusion in the cyclodextrin cavity and anionic exchange between the bromide ions of the phosphonium groups and perchlorate anions. Under optimized functionalization conditions, EIS reveals high sensitivity and selectivity, achieving a record-low detection limit (LOD) of ~10⁻¹² M and a wide linear range of detection (10⁻¹¹ M–10⁻⁴ M). Sensing mechanisms at the functionalized transducer interfaces are examined through numerical fitting of Cole-Cole impedance spectra via a single relaxation equivalent circuit. Real water sample analysis confirms the sensor’s practical applicability, with recoveries between 96.9% and 109.8% and RSDs of 2.4–4.8%. Finally, a comparative study with reported membrane sensors shows that β-CDP offers superior performance, wider range, higher sensitivity, lower LOD, and simpler synthesis. Full article

Network polymers with β-cyclodextrin moieties were prepared by nucleophilic substitution reactions between polyamines, linear polyethyleneimine (LPEI), polyallylamine (PAA), (ε-poly-L-lysine) (EPL), and monochlorotriazinyl-β-cyclodextrin (MCTCD) in methanol/water mixed solvent or water. The reactions under conditions of high material concentration (30 wt%) and a feed ratio of [MCT]/[NH] = 0.5 (mol/mol) successfully yield porous polymers via reaction-induced phase separation. The molecular structure of the polyamines and reaction conditions strongly affected the morphology of the resulting porous polymers. The porous polymers were composed of connected particles, gathered (slightly connected) particles, and/or disordered bulky structures, with sizes of 10⁻⁹ m–10⁻⁸ m. An increase in the molecular weight of LPEI and PAA and the feed molar ratio of [MCT]/[NH] tended to decrease the particle size. Young’s moduli of the LPEI-MCTCD and PAA-MCTCD porous polymers increased with an increase in bulk density, which was derived from small particle sizes. The wide particle size distribution and disordered structure caused collapse by the compression under 50 N of pressure. An LPEI-MCTCD adsorbed methyl orange, methylene blue, and phenolphthalein through ionic interactions, π–π interaction, and/or β-cyclodextrin inclusion. Full article