Polymers Enhance Chlortetracycline Hydrochloride Solubility.

Chlortetracycline hydrochloride (CTC) is a broad-spectrum tetracycline antibiotic with a wide range of antibacterial activities. Due to low solubility, poor stability, and low bioavailability, clinical preparation development is limited. We sought to improve these solubility and dissolution rates by preparing solid dispersions. A hydrophilic polymer was selected as the carrier, and a solid dispersion was prepared using a medium grinding method, with samples characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), and particle size distribution (PSD). To maximize CTC solubility and stability, different polymer types and optimal drug-to-polymer ratios were screened. The solubility of optimized povidone K30 (PVPK30) (1/0.75, w/w)-, hydroxypropyl-ß-cyclodextrin (HP-ß-CD) (1/2, w/w)-, and gelatin (1/1, w/w)-based solid dispersions was 6.25-, 7.7-, and 3.75-fold higher than that of pure CTC powder, respectively. Additionally, in vitro dissolution studies showed that the gelatin-based solid dispersion had a higher initial dissolution rate. SEM and PS analyses confirmed that this dispersion had smaller and more uniform particles than PVPK30 and HP-ß-CD dispersions. Therefore, successful solid polymer dispersion preparations improved the CTC solubility, dissolution rates, and stability, which may have potential as drug delivery systems.

Formulation and Development of Nanofiber-Based Ophthalmic Insert for the Treatment of Bacterial Conjunctivitis.

A novel ophthalmic delivery system utilizing levofloxacin-loaded, preservative-free, nanofiber-based inserts was investigated. Polyvinyl alcohol (PVA) and Poloxamer 407 (Polox)were employed as matrix materials, while hydroxypropyl-beta-cyclodextrin (HP-ß-CD) was a solubilizer. The formulations were prepared via electrospinning and characterized for fiber morphology, drug dissolution, cytotoxicity, and antimicrobial activity. Scanning electron microscopy confirmed uniform fibrous structures. Fourier Transform Infrared spectroscopy and X-ray diffraction analyses demonstrated the amorphous state of levofloxacin within the fibers. In vitro dissolution studies revealed a rapid (within 2 min) and complete drug release, with higher HP-ß-CD levels slightly delaying the release. Cytotoxicity tests showed increased HP-ß-CD concentrations induced irritation, that was mitigated by sodium hyaluronate. The antimicrobial efficacy of the nanofibers was comparable to conventional eye drops, with lower minimum inhibitory concentrations for most tested strains. The nanofibrous formulation prepared from a PVA-Polox-based viscous solution of the drug:CD 1:1 mol ratio, containing 0.4% (w/w) sodium hyaluronate) was identified as a particularly promising alternative formulation due to its rapid and complete dissolution, good biocompatibility, and effective antimicrobial properties. Its gelling properties indicate that the residence time on the eye surface can be increased, potentially reducing discomfort and enhancing therapeutic outcomes. The nanofibrous formulations enhanced antimicrobial efficacy, providing a preservative-free alternative that minimizes the potential eye irritation that might occur because of the preservative agent and reduces the administrated dose frequency by extending the drug's retention time on the eye's surface. Subsequently, it improves patients' adherence, which would reflect positively on the bioavailability. The levofloxacin-HP-ß-CD nanofibers demonstrate promise as an alternative to traditional eye drops, offering advantages in solubility, stability, and patient compliance for ocular infection treatment.

Cross-Linked Thiolated Hydroxypropil-ß-Cyclodextrin for Pulmonary Drug Delivery.

Inhalable formulations with cyclodextrins (CDs) as solubility and absorption enhancers show promise for pulmonary delivery. Thiolated hydroxypropyl-ß-cyclodextrin (HP-ß-CD-SH) has mucoadhesive properties, enhancing drug absorption. Moreover, it has self-aggregation capability, which could further improve absorption and drug stability, as well as reduce irritation. This study aims to stabilize CD nanoaggregates using bifunctional cross-linkers and evaluate their benefits for lung drug delivery compared to pristine HP-ß-CD-SH. METHODS: The effectiveness of cross-linked HP-ß-CD-SH nanoparticles (HP-ß-CD-SH-NP) was compared to transient nanoaggregates in enhancing the activity of dexamethasone (DMS) and olive leaf extracts (OLE). DMS, a poorly soluble drug commonly used in lung treatments, and OLE, known for its antioxidant properties, were chosen. Drug-loaded HP-ß-CD-SH-NP were prepared and nebulized onto a lung epithelial Air-Liquid Interface (ALI) model, assessing drug permeation and activity. RESULTS: HP-ß-CD-SH with 25% thiolation was synthesized via microwave reaction, forming 150 nm nanoaggregates and stabilized 400 nm HP-ß-CD-SH-NP. All carriers showed good complexing ability with DMS and OLE and were biocompatible in the lung ALI model. HP-ß-CD-SH promoted DMS absorption, while stabilized HP-ß-CD-SH-NP protected against oxidative stress. CONCLUSION: HP-ß-CD-SH is promising for lung delivery, especially as stabilized nanoaggregates, offering versatile administration for labile molecules like natural extracts.

In vitro and in silico studies of the inclusion complexation of 8-bromobaicalein with ß-cyclodextrins.

Baicalein, a flavone derived from Scutellaria baicalensis Georgi, exhibits potent anti-inflammatory, antiviral, and anticancer properties. Its derivative, known as 8-bromobaicalein (BB), has been found to have strong cytotoxic effect on MCF-7 human breast cancer cells. However, its limited solubility in water has hindered its potential for wider applications. To address this issue, we investigated the use of cyclodextrins specifically ßCD, 2,6-di-O-methyl-ß-cyclodextrin (DMßCD), and hydroxypropyl-ß-cyclodextrin (HPßCD) to improve the solubility of BB through inclusion complexation. During 250 ns molecular dynamics simulations, it was found that BB can form inclusion complexes with all ßCDs. These complexes exhibit two distinct orientations: chromone group insertion (C-form) and phenyl group insertion (P-form). The formation of these complexes is primarily driven by van der Waals interactions. DMßCD has the highest number of atom contacts with BB and the lowest solvent accessibility in the hydrophobic cavity. These results coincide with the highest binding affinity from the MM/GBSA-based free energy calculation method. Experimental phase solubility diagrams revealed a 1:1 stoichiometric ratio (AL type) between BB and ßCDs, in which BB/DMßCD showed the highest stability. The formation of inclusion complexes was confirmed by differential scanning calorimetry and scanning electron microscope methods. Additionally, the BB/DMßCD inclusion complex demonstrated significantly higher anticancer activity against MCF-7 human breast cancer cells compared to BB alone. These findings underscore the potential of DMßCD for formulating BB in pharmaceutical and medical applications.

Preparation, solubility, and anti-inflammatory effects of a complex of diphenylcyclopropenone/ß-cyclodextrin derivatives as the treatment of alopecia areata.

Purpose: To investigate the preparation of inclusion complexes of diphenylcyclopropenone (DPCP)/ß-cyclodextrin (ß-CD) derivatives using a three-dimensional (3D) ball mill, and verify the inclusion behavior of the solid dispersion. Additionally, we aimed to investigate the effect of DPCP/ß-CDs complex formation on the spleens of male C57BL/6 mice in terms of anti-inflammatory effects. Methods: The inclusion complexes of DPCP with ß-CD and hydroxypropyl-ß-cyclodextrin (HPßCD) were prepared using a 3D ball mill. Powder X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to evaluate the solid-state properties. The solubility of the prepared DPCP/ß-CD and HPßCD complexes and the intermolecular interaction between DPCP and ß-CD derivatives in solution were assessed using 1H nuclear magnetic resonance (NMR). Furthermore, the anti-inflammatory effects of DPCPs in the prepared DPCP/CD complexes were investigated using spleens from male C57BL/6 mice, with measurement of interferon gamma (IFN-γ) secretion as an endpoint. Additionally, the protective effects of each drug on NIH-3T3 cells exposed to ultraviolet (UV) irradiation were examined. Results: Solid-state characterization confirmed the formation of inclusion complexes in the 3D ground mixture (3DGM) (DPCP/ß-CD = 1/1) and 3DGM (DPCP/HPßCD = 1/1) complexes through PXRD and IR analysis. The solubility of 3DGM (DPCP/ß-CD = 1/1) and 3DGM (DPCP/HPßCD = 1/1) was 17.5 µg/mL and 58.4 µg/mL, respectively, indicating higher solubility than that of DPCP alone. NMR analysis of 3DGM samples suggested that DPCP/ß-CD and DPCP/HPßCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. Regarding the anti-inflammatory activity of DPCP, 3DGM (DPCP/HPß-CD) showed anti-inflammatory effects at lower doses compared to 3DGM (DPCP/ß-CD) in terms of IFN-γ and NIH-3T3 cells injured by UV irradiation. Conclusion: We successfully formed inclusion complexes of DPCP/ß-CD and DPCP/HPßCD using the 3D ground mixture method. NMR analysis suggested that DPCP/ß-CD and DPCP/HPßCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. The anti-inflammatory activity of DPCP was more pronounced in 3DGM (DPCP/HPßCD) at lower doses compared to that in 3DGM (DPCP/ß-CD), indicating that the HPßCD derivatives were more effective in enhancing the anti-inflammatory properties of DPCP.

7-Phenylheptanoic Acid-Hydroxypropyl ß-Cyclodextrin Complex Slows the Progression of Renal Failure in Adenine-Induced Chronic Kidney Disease Mice.

The characteristic accumulation of circulating uremic toxins, such as indoxyl sulfate (IS), in chronic kidney disease (CKD) further exacerbates the disease progression. The gut microbiota, particularly gut bacterial-specific enzymes, represents a selective and attractive target for suppressing uremic toxin production and slowing the progression of renal failure. This study investigates the role of 4-phenylbutyrate (PB) and structurally related compounds, which are speculated to possess renoprotective properties in suppressing IS production and slowing or reversing renal failure in CKD. In vitro enzyme kinetic studies showed that 7-phenylheptanoic acid (PH), a PB homologue, suppresses the tryptophan indole lyase (TIL)-catalyzed decomposition of tryptophan to indole, the precursor of IS. A hydroxypropyl ß-cyclodextrin (HPßCD) inclusion complex formulation of PH was prepared to enhance its biopharmaceutical properties and to facilitate in vivo evaluation. Prophylactic oral administration of the PH-HPßCD complex formulation reduced circulating IS and attenuated the deterioration of renal function and tubulointerstitial fibrosis in adenine-induced CKD mice. Additionally, treatment of moderately advanced adenine-induced CKD mice with the formulation ameliorated renal failure, although tissue fibrosis was not improved. These findings suggest that PH-HPßCD can slow the progression of renal failure and may have implications for preventing or managing CKD, particularly in early-stage disease.

Risperidone-cyclodextrin complex reservoir combined with hydrogel-forming microneedle array patches for enhanced transdermal delivery.

Hydrogel-forming microneedle array patches (HFMAPs) are microneedles that create microconduits upon insertion and swelling in the skin, potentially allowing prolonged drug delivery without generating sharps waste. Delivering hydrophobic drugs using HFMAPs poses challenges, which can be addressed using solubility enhancers such as cyclodextrins (CDs). This study aimed to deliver risperidone (RIS) transdermally using HFMAPs. To enhance the aqueous solubility of RIS hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD) were utilised and their performance was tested using phase solubility studies. The aqueous solubility of RIS was enhanced by 4.75-fold and 2-fold using HP-ß-CD and HP-γ-CD, respectively. RIS-HP-ß-CD complex (CX) and physical mixture (PM) directly compressed tablets were prepared and combined with HFMAPs. Among the tested formulations, RIS-HP-ß-CD PM reservoirs with 11 x 11 PVA/PVP HFMAPs exhibited the best performance in ex vivo studies and were further evaluated in in vivo experiments using female Sprague Dawley rats. The extended wear time of the MAPs resulted in the sustained release of RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in plasma samples, lasting from 3 to 5 days with a 1-day application and up to 10 days with a 5-day application. For a 1-day application, HFMAPs showed greater systemic exposure to RIS compared to intramuscular control (AUC0-t: 13330.05 ± 2759.95 ng/mL/hour versus 2706 ± 1472 ng/mL/hour). Moreover, RIS exposure was extended to 5 days (AUC0-t: 12292.37 ± 1801.94 ng/mL/hour). In conclusion, HFMAPs could serve as an alternative for delivering RIS in a sustained manner, potentially improving the treatment of schizophrenia.

Understanding Glucagon Aggregation: In Silico Insights and Experimental Validation.

Peptide aggregation poses a significant challenge in biopharmaceutical development and neurodegenerative diseases. This study combines computational simulations and experimental validation to uncover the underlying mechanisms and countermeasures for the aggregation of glucagon, a peptide with a high tendency to aggregate. In silico simulations demonstrate that lactose and 2-hydroxypropyl-ß-cyclodextrin (2-HPßCD) influence glucagon aggregation differently: lactose stabilizes glucagon by increasing the α-helical content, while 2-HPßCD disrupts protein-protein interactions. According to the simulations, 2-HPßCD is particularly effective at preserving the monomeric form of glucagon. Experimental validation with microfluidic modulation spectroscopy (MMS) confirms these findings, showing that glucagon in the presence of 2-HPßCD remains structurally stable, supporting the antiaggregation effect of this excipient. This research provides essential insights into glucagon aggregation obtained through a new powerful tool for monitoring the critical properties of peptide aggregation, suggesting new strategies for addressing this challenge in therapeutic peptide development.

PCL/Locust bean gum nanofibers loaded with HP-ß-CD/Epicatechin clathrate compounds for fruit packaging.

In this work, the hydroxypropyl-ß-cyclodextrin (HP-ß-CD)/Epicatechin (EC) clathrate compounds were rapidly prepared based on an ultrasound-mediated method, and Polycaprolactone (PCL)/Locust bean gum (LBG) nanofibers loaded clathrate compounds were fabricated by electrostatic spinning (ELS) for fruit packaging. The results of infrared spectrum and crystal type analysis proved that clathrate compounds were successfully prepared. With the addition of clathrate compounds, the diameter of fibers increased from 553.43 to 1273.47 nm, and hydrogen bonds were formed between clathrate compounds and fibrous membranes, which improved the thermal stability, reduced the crystallinity, and enhanced the hydrophilicity and gas permeability of fibrous membranes. The fibrous membranes indicated sustained release of EC for 240 h, retaining the activity of EC and demonstrating good bacteriostatic ability in vitro and in vivo. The test results showed that the antibacterial fibrous membranes prepared in this work have a positive application prospect for fruit packaging.

Preparation, Characterization, and Oral Bioavailability of Solid Dispersions of Cryptosporidium parvum Alternative Oxidase Inhibitors.

The phenylpyrazole derivative 5-amino-3-[1-cyano-2-(3-phenyl-1H-pyrazol-4-yl) vinyl]-1-phenyl-1H-pyrazole-4-carbonitrile (LN002), which was screened out through high-throughput molecular docking for the AOX target, exhibits promising efficacy against Cryptosporidium. However, its poor water solubility limits its oral bioavailability and therapeutic utility. In this study, solid dispersion agents were prepared by using HP-ß-CD and Soluplus® and characterized through differential scanning calorimetry, Fourier transform infrared, powder X-ray diffraction, and scanning electron microscopy. Physical and chemical characterization showed that the crystal morphology of LN002 transformed into an amorphous state, thus forming a solid dispersion of LN002. The solid dispersion prepared with an LN002/HP-ß-CD/Soluplus® mass ratio of 1:3:9 (w/w/w) exhibited significantly increased solubility and cumulative dissolution. Meanwhile, LN002 SDs showed good preservation stability under accelerated conditions of 25 °C and 75% relative humidity. The complexation of LN002 with HP-ß-CD and Soluplus® significantly improved water solubility, pharmacological properties, absorption, and bioavailability.

Accumulation of alkyl-lysophosphatidylcholines in Niemann-Pick disease type C1.

Lysosomal function is impaired in Niemann-Pick disease type C1 (NPC1), a rare and inherited neurodegenerative disorder, resulting in late endosomal/lysosomal accumulation of unesterified cholesterol. The precise pathogenic mechanism of NPC1 remains incompletely understood. In this study, we employed metabolomics to uncover secondary accumulated substances in NPC1. Our findings unveiled a substantial elevation in the levels of three alkyl-lysophosphatidylcholine [alkyl-LPC, also known as lyso-platelet activating factor (PAF)] species in NPC1 compared to controls across various tissues, including brain tissue from individuals with NPC1, liver, spleen, cerebrum, cerebellum, and brain stem from NPC1 mice, as well as in both brain and liver tissue from NPC1 cats. The three elevated alkyl-LPC species were as follows: LPC O-16:0, LPC O-18:1, and LPC O-18:0. However, the levels of PAF 16:0, PAF 18:1, and PAF 18:0 were not altered in NPC1. In the NPC1 feline model, the brain and liver alkyl-LPC levels were reduced following 2-hydroxypropyl-ß-cyclodextrin (HPßCD) treatment, suggesting that alkyl-LPCs are secondary storage metabolites in NPC1 disease. Unexpectedly, cerebrospinal fluid (CSF) levels of LPC O-16:0 and LPC O-18:1 were decreased in individuals with NPC1 compared to age-appropriate comparison samples, and their levels were increased in 80% of participants 2 years after intrathecal HPßCD treatment. The fold increases in CSF LPC O-16:0 and LPC O-18:1 levels were more pronounced in responders compared to nonresponders. This study identified alkyl-LPC species as secondary storage metabolites in NPC1 and indicates that LPC O-16:0 and LPC O-18:1, in particular, could serve as potential biomarkers for tracking treatment response in NPC1 patients.

Impact of 2-hydroxypropyl-ß-cyclodextrin inclusion complex formation on dopamine receptor-ligand interaction - A case study.

The octanol-water distribution coefficient (logP), used as a measure of lipophilicity, plays a major role in the drug design and discovery processes. While average logP values remain unchanged in approved oral drugs since 1983, current medicinal chemistry trends towards increasingly lipophilic compounds that require adapted analytical workflows and drug delivery systems. Solubility enhancers like cyclodextrins (CDs), especially 2-hydroxypropyl-ß-CD (2-HP-ß-CD), have been studied in vitro and in vivo investigating their ADMET (adsorption, distribution, metabolism, excretion and toxicity)-related properties. However, data is scarce regarding the applicability of CD inclusion complexes (ICs) in vitro compared to pure compounds. In this study, dopamine receptor (DR) ligands were used as a case study, utilizing a combined in silico/in vitro workflow. Media-dependent solubility and IC stoichiometry were investigated using HPLC. NMR was used to observe IC formation-caused chemical shift deviations while in silico approaches utilizing basin hopping global minimization were used to propose putative IC binding modes. A cell-based in vitro homogeneous time-resolved fluorescence (HTRF) assay was used to quantify ligand binding affinity at the DR subtype 2 (D2R). While all ligands showed increased solubility using 2-HP-ß-CD, they differed regarding IC stoichiometry and receptor binding affinity. This case study shows that IC-formation was ligand-dependent and sometimes altering in vitro binding. Therefore, IC complex formation can't be recommended as a general means of improving compound solubility for in vitro studies as they may alter ligand binding.

Preparation of chitosan photodynamic antibacterial film loaded with VK3 complex in the preservation of chilled mutton.

To effectively utilize the photodynamic antibacterial ability of vitamin K3 (VK3), by solving the photothermal instability of VK3, it was combined with natural polymers to apply the preservation of chilled mutton. We encapsulated VK3 in the (2-Hydroxypropyl)-ß-cyclodextrin (HP-ß-CD) to construct VK3-HP-ß-CD complex and then introduced the complex to chitosan (CS) and polyvinyl alcohol (PVA) to fabricate an antibacterial film (CS/PVA-VK3-HP-ß-CD film). Through the packaging performance test of the film, the content of VK3-HP-ß-CD was an important factor determining the properties of film including tensile strength, elongation at break, water vapor permeability, water content and water contact angle. Meanwhile, CS/PVA-VK3-HP-ß-CD films could continuously release ROS under light and suspended in dark, thus realizing >99 % antibacterial rate for Escherichia coli and Staphylococcus aureus. In the application experiment of chilled mutton, CS/PVA-VK3-1-HP-ß-CD film could significantly inhibit the increase of total viable count (TVC), pH value (pH) and total volatile base nitrogen (TVB-N) of chilled mutton, and extended its shelf life for at least 12 days. These results indicated that the CS/PVA film with the VK3-HP-ß-CD complex might have promising potential as an antibacterial material for packaging and preserving food.

Formation of amygdalin/ß-cyclodextrin derivatives inclusion complexes for anticancer activity assessment in human cervical carcinoma HeLa cell line.

Nanoencapsulation has gained considerable attention because of its unique features and advantages in anticancer drug delivery. Amygdalin (AMY) is an anticancer compound, showing limitations in its applications by low stability. Herein, the inclusion complexes (ICs) of AMY with ß-cyclodextrin (ßCD), and its derivatives such as 2-hydroxypropyl-ßCD (HPßCD) and methyl-ßCD (MßCD) were fabricated. The fabricated AMY/CD-ICs were thoroughly evaluated using Fourier-transform infrared spectroscopy, powder X-ray diffraction, thermogravimetric/differential thermal analysis, proton nuclear magnetic resonance, ultraviolet-visible diffuse reflectance spectroscopy, and photoluminescence techniques. Double reciprocal profile study of the absorption and fluorescence spectra revealed that the AMY formed the ICs with ßCD derivatives at a guest/host stoichiometric ratio of 1/1. The thermal stability of AMY was enhanced as the IC formation aid observed by the shift of thermal degradation temperature of AMY from the range of âˆ¼ 220-250 °C to > 295 °C. Theoretical analyses of the energetic, electronic, and global reactivity parameters of the AMY/CD-ICs were evaluated using the PM3 method. Further assessment of the dissolution diagrams of AMY/CD-ICs revealed a burst release profile. In addition, cell toxicity was evaluated using the MTT assay, and the results showed that AMY/CD-ICs had significantly more efficacious in inhibiting HeLa cancer cells than AMY. These results proved that the IC formations with CDs significantly enhanced the anticancer activity of AMY.

Micellar-type aggregates of HP-ß-CD/GML inclusion complex: Increased water-solubility and effective antibacterial capabilities.

The inclusion complex (IC) was successfully obtained by encapsulating glycerol monolaurate (GML) into the cavity of hydroxypropyl-ß-cyclodextrin (HP-ß-CD). Compared with solubility of pure GML <80 µg/mL in water, and the water-solubility of encapsulated GML was significantly improved and reached to 270,000 µg/mL. IC can form nanoparticles by self-assembly, probably assigned to its strong capability to form micellar-type aggregates. A Higuchi's AL-type phase-solubility diagram indicated the strong interaction between host and guest molecules with the formation of 1:1 GML/HP-ß-CD complex and the stability constant at 6248 L/mol. Compared with pure GML, encapsulated GML at the same concentration can also show good antibacterial capabilities against S. aureus and E. coli in sterile water, and the effective preservative capabilities towards beef meatballs. The boosted enhancement in water-solubility of GML and the effective antibacterial capabilities endowed IC with potential in the application of food decontamination.

Preparation and characterization of fennel (Foeniculum vulgare miller) essential oil/hydroxypropyl-ß-cyclodextrin inclusion complex and its application for chilled pork preservation.

Fennel essential oil (FEO) a natural spice that has versatile biological activities. However, the direct use of FEO is limited due to its water insolubility and poor stability. Chilled pork is prone to spoilage during storage. To solve these problems, this study aimed to prepare an inclusion complex (IC) of FEO with hydroxypropyl-ß-cyclodextrin via co-precipitation and apply it to the preservation of chilled pork. Results indicated that the optimal parameters were encapsulating temperature 37 °C, wall-core ratio 14:1 g/mL, stirring speed 600 r/min, and encapsulating time 240 min, obtaining an encapsulation efficiency of 83.75%. The results of scanning electron microscopy, Fourier transform infra-red spectroscopy, and nuclear magnetic resonance demonstrated the successful preparation of IC. The release of FEO from IC was controllable through adjusting the different temperatures and relative humidities. Furthermore, IC effectively delayed the spoilage of chilled pork and extended its shelf life by 6 days at 4 °C.

"Reservoir-law" synergistic reinforcement of electrostatic spun polylactic acid composites with cellulose nanocrystals and 2-hydroxypropyl-ß-cyclodextrin for intelligent bioactive food packaging.

Cellulose nanocrystals (CNCs) were obtained from the extraction and bleaching of jute cellulose as the enhancer, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as the carrier, the flavonoids-anthocyanidins and cinnamaldehyde as the bioactive agent, and finally a novel kind of polylactic acid (PLA)-based composite membrane was derived by electrostatic spun method. With the increasing concentration, HP-ß-CDs cooperated with CNCs to regulate or control the release rate of bioactive compounds, which had a synergistic effect on the performance of the PLA matrix. The mechanical strength of PLA-3.2 composite with tannic acid (TA) surface cross-linking was 29.6 % higher than neat PLA, and could also continuously protect cells from oxidative stress and free radicals. In addition, excellent cell biocompatibility was found, and attributed to the interaction between bioactive compounds and cell membrane. In addition, we also found two excellent properties from our experimental results: obvious intelligent color reaction and good antibacterial ability. Finally, PLA-3.2 composites could be degraded by soil and are conducive to plant root growth. Hence, this work could solve many of the current problems of biodegradability and functionality of biopolymers for potential applications in areas such as intelligent bioactive food packaging.

Supersaturated Drug Delivery System of Oxyberberine Based on Cyclodextrin Nanoaggregates: Preparation, Characterization, and in vivo Application.

Propose: Oxyberberine (OBB), one of the main metabolites of berberine derived from intestinal and erythrocyte metabolism, exhibits appreciable anti-hyperuricemic activity. However, the low water solubility and poor plasma concentration-effect relationship of OBB hamper its development and utilization. Therefore, an OBB-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) supersaturated drug delivery system (SDDS) was prepared and characterized in this work. Methods: OBB-HP-ß-CD SDDS was prepared using the ultrasonic-solvent evaporation method and characterized. Additionally, the in vitro and in vivo release experiments were conducted to assess the release kinetics of OBB-HP-ß-CD SDDS. Subsequently, the therapeutic efficacy of OBB-HP-ß-CD SDDS on hyperuricemia (HUA) was investigated by means of histopathological examination and evaluation of relevant biomarkers. Results: The results of FT-IR, DSC, PXRD, NMR and molecular modeling showed that the crystallized form of OBB was transformed into an amorphous OBB-HP-ß-CD complex. Dynamic light scattering indicated that this system was relatively stable and maintained by formation of nanoaggregates with an average diameter of 23 nm. The dissolution rate of OBB-HP-ß-CD SDDS was about 5 times higher than that of OBB raw material. Furthermore, the AUC0-t of OBB-HP-ß-CD SDDS (10.882 µg/mL*h) was significantly higher than that of the raw OBB counterpart (0.701 µg/mL*h). The oral relative bioavailability of OBB-HP-ß-CD SDDS was also enhanced by 16 times compared to that of the raw material. Finally, in vivo pharmacodynamic assay showed the anti-hyperuricemic potency of OBB-HP-ß-CD SDDS was approximately 5-10 times higher than that of OBB raw material. Conclusion: Based on our findings above, OBB-HP-ß-CD SDDS proved to be an excellent drug delivery system for increasing the solubility, dissolution, bioavailability, and anti-hyperuricemic potency of OBB.

Preparation, characterization and evaluation of HPßCD-PTX/PHB nanoparticles for pH-responsive, cytotoxic and apoptotic properties.

Paclitaxel (PTX) is a potent anticancer drug. However, PTX exhibits extremely poor solubility in aqueous solution along with severe side effects. Therefore, in this study, an inclusion complex was prepared between PTX and hydroxypropyl-ß-cyclodextrin (HPßCD) by solvent evaporation to enhance the drug's solubility. The HPßCD-PTX inclusion complex was then encapsulated in poly-3-hydroxybutyrate (PHB) to fabricate drug-loaded nanoparticles (HPßCD-PTX/PHB NPs) by nanoprecipitation. The HPßCD-PTX/PHB NPs depicted a higher release of PTX at pH 5.5 thus demonstrating a pH-dependent release profile. The cytotoxic properties of HPßCD-PTX/PHB NPs were tested against MCF-7, MDA-MB-231 and SW-620 cell lines. The cytotoxic potential of HPßCD-PTX/PHB NPs was 2.59-fold improved in MCF-7 cells in comparison to free PTX. Additionally, the HPßCD-PTX/PHB NPs improved the antimitotic (1.68-fold) and apoptotic (8.45-fold) effects of PTX in MCF-7 cells in comparison to PTX alone. In summary, these pH-responsive nanoparticles could be prospective carriers for enhancing the cytotoxic properties of PTX for the treatment of breast cancer.

Hyaluronic acid-based multifunctional bio-active coating integrated with cinnamaldehyde/hydroxypropyl-ß-cyclodextrin inclusion complex for fruit preservation.

Natural preservatives such as cinnamaldehyde (CIN) are garnering increasing interest to replace their synthetic counterparts in maintaining fruit freshness and safety. However, their long-term effectiveness and widespread application have been greatly limited due to high volatility and potent aroma. To address these challenges, we developed a viable and simple strategy to prepare a multifunctional active coating for fruit preservation by incorporating host-guest inclusion complex of CIN and 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) CIN@HP-ß-CD into hyaluronic acid (HA), a natural polysaccharide with exceptional film-forming properties. The as-prepared HA/CIN@HP-ß-CD coatings exhibited universal surface affinity, excellent antimicrobial performance, and satisfactory antioxidant properties with no potential toxicity. Release kinetic studies have demonstrated that CIN in the coating is continuously and slowly released. Furthermore, freshness preservation experiments on bananas and fresh-cut apples demonstrated that the developed coating is effective in preserving the color of fruit, decreasing the weight loss rate, preventing the microorganism's growth, and significantly extending the period of freshness, exhibiting the potential for application in fruit preservation.