Rapid isolation of extracellular vesicles using covalent organic frameworks combined with microfluidic technique.

Extracellular vesicles (EVs) are nano-sized lipid-membrane vesicles involved in intercellular communication and reflecting the physiological and pathological processes of their parental cells. Rapid isolation of EVs with low cost is an essential precondition for downstream function exploration and clinical applications. In this work, we designed a novel EVs isolation device based on the boronated organic framework (BOF) coated recyclable microfluidic chip (named EVs-BD) to separate EVs from cell culture media. Using a reactive oxygen species responsive phenylboronic ester compound, the highly porous BOF with a pore size in the range of 10-300 nm was prepared by crosslinking γ-cyclodextrin metal-organic frameworks. A mussel-inspired polydopamine (PDA)/polyethyleneimine (PEI) coating was employed to pattern BOF on the PDMS substrate of microfluidic channels. The EVs-BD was demonstrated to offer distinct advantages over the traditional ultracentrifugation method, such as operation simplicity and safety, reduced time and expense, and low expertize requirements. All things considered, a novel approach of EV acquisition has been successfully developed, which can be customized easily to meet the requirements of various EV-relevant research.

Supramolecular Structure of the ß-Cyclodextrin Metal-Organic Framework Optimizes Iodine Stability and Its Co-delivery with l-Menthol for Antibacterial Applications.

The spread of upper respiratory tract (URT) infections harms people's health and causes social burdens. Developing targeted treatment strategies for URT infections that exhibit good biocompatibility, stability, and strong antimicrobial effects remains challenging. The dual antimicrobial and antiviral effects of iodine (I2) in combination with the cooling sensation of l-menthol in the respiratory tract can simultaneously alleviate URT inflammation symptoms. However, as both I2 and l-menthol are volatile, addressing stability issues is crucial. In this study, a potassium iodide ß-cyclodextrin metal-organic framework [ß-CD-POF(I)] with appropriate particle size was used to coload and deliver I2 and l-menthol. Primarily, ß-CD-POF(I) was employed as the most efficient carrier to significantly enhance the stability of I2, surpassing any other known protection strategies in the pharmaceutical field (CD complexations, PVP conjugations, and cadexomer iodine). The mechanism underlying the improvement in stability of I2 by ß-CD-POF(I) was investigated through scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and molecular docking. The results revealed that the key processes involved in improving stability were the inclusion of I2 by ß-CD cavities in ß-CD-POF(I) and the formation of polyiodide anion between iodine ions and I2. Furthermore, the potential of ß-CD-POF(I) to load and deliver drugs was validated, and coloading of l-menthol and I2 demonstrated reliable stability. ß-CD-POF(I) achieved a rate of URT deposition ≥95% in vitro, and the combined antibacterial effects of coloaded I2 and l-menthol was better than I2 or PVP-I alone, with no irritation noted following URT administration in rabbits. Therefore, the stable coloading of drugs by ß-CD-POF(I), leading to enhanced antimicrobial effects, provides a new strategy for treating URT infections.

Cyclodextrin MOFs modified dry powder inhalers quadruple bioavailability of luteolin to ameliorate fibrosing interstitial lung disease.

Fibrosing interstitial lung disease (ILD) is a pathological condition that is highly heterogeneous and lethal, and has few effective treatment choices. Other than pirfenidone and nintedanib for the therapy of idiopathic pulmonary fibrosis, no medications are currently licensed for the treatment of ILD. Luteolin is a common flavonoid with multiple biological effects such as anti-inflammation but with poor solubility and absorption. In this study, we loaded luteolin into γ-cyclodextrin metal-organic frameworks (CD-MOFs) to deliver the medicine to the lungs using dry powder inhalers; in vitro pulmonary deposition results showed LUT@CDMOF had a high fine particle fraction (FPF) (59.77 ± 3.48%). LUT@CDMOF effectively inhibited ILD progression in the BLM-induced fibrosing ILD model rats. When compared to oral administration, the inhalation of LUT@CDMOF dry powder in rats showed considerable improvements in absorption and bioavailability, with a tmax of 0.08 h and a high absolute bioavailability (82%) of LUT (The AUC(0-t) and Cmax of inhal. LUT@CDMOF respectively increased about 4.03 times and 9.11 times, when compared with the i.g. LUT group). These studies demonstrate the potent anti-inflammatory activities of LUT@CDMOF. The inhaled LUT@CDMOF might be considered as a promising new strategy in the treatment of fibrosing ILD.

Antioxidant Biodegradable Covalent Cyclodextrin Frameworks as Particulate Carriers for Inhalation Therapy against Acute Lung Injury.

Drug therapies for acute lung injury (ALI) are far from satisfactory, primarily because drugs cannot specifically target the lungs. Direct delivery of drugs to the deep alveolar regions by inhalation administration is crucial for the treatment of ALI. However, conventional inhalable carriers such as lactose and mannitol are generally inactive. Therefore, the use of a novel pharmacologically active carrier for pulmonary delivery may produce synergetic effects in treating ALI. Considering the pathophysiological environment of ALI, which typically featured excessive reactive oxygen species (ROS) and acute inflammation, we synthesized a novel kind of biodegradable and ROS-sensitive cross-linked covalent cyclodextrin frameworks (OC-COF) with uniform inhalable particle size to treat ALI. OC-COF was devised to incorporate H2O2-scavenging peroxalate ester linkages, which could hydrolyze and eliminate ROS generated in inflammatory sites. Ligustrazine (LIG), an antioxidant and anti-inflammatory natural compound, was loaded into OC-COF and evaluated as a dry powder inhaler (LIG@OC-COF) in vitro and in vivo, showing favorable aerodynamic properties and prominent antioxidant and anti-inflammatory capacities for the synergistic effects of OC-COF and LIG. In ALI rats, inhalation of LIG@OC-COF with a one-fifth LIG dose significantly alleviated the inflammation, oxidant stress, and lung damage. Western blot analysis demonstrated that LIG@OC-COF protected the lungs by regulating the Nrf2/NF-κB signaling pathway. In summary, this study provides a novel ROS-responsive material as an inhalable particulate carrier for the improved treatment of ALI and other medical conditions.

Particle Design and Inhalation Delivery of Iodine for Upper Respiratory Tract Infection Therapy.

Diseases caused by upper respiratory tract (URT) and pulmonary infections have been a serious threat to human health for millennia and lack of targeted effective therapeutic techniques. In this study, two kinds of cyclodextrin particles with typical particle shapes of nanocubes and microbars were synthesized through a facile process. Subsequently, the particles were used as carriers for loading and stabilizing iodine and characterizations were performed to demonstrate the loading mechanism. Next-generation impactor (NGI) experiments showed that iodine-loaded microbars (I2@microbars) had a deposition rate of 79.75% in URT, while iodine-loaded nanocubes (I2@nanocubes) were delivered to the deep lungs with a fine particle fraction (FPF) of 46.30%. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) indicated that the iodine-loaded nanocubes and microbars had similar bactericidal effect to povidone iodine solution. Cell viability studies and extracellular pro-inflammatory factor (TNF-α, IL-1ß, IL-6) evaluations demonstrate noncytotoxic effects of the blank carriers and anti-inflammatory effects of iodine-loaded samples. The irritation of the rat pharynx by I2@microbars was evaluated for the behavioral observations, body weight changes, histopathological studies, and TNF-α, IL-1ß, and IL-6 levels in pharyngeal tissues. The results showed that I2@microbars had no irritation to rat pharyngeal tissues at therapeutic doses. In conclusion, the present study provides novel treatment of URT infections via supramolecular cyclodextrin carriers for URT local therapy with iodine loading by a solvent-free method, which enhances the stability and reduces the inherent irritation without inhibiting their antimicrobial effects. Two kinds of cyclodextrin particles with typical shapes of microbars and nanocubes were synthesized by a facile process. Subsequently, iodine was successfully loaded into the particles by gas-solid interaction. The iodine-loaded microbars showed air dynamics characteristics for inhalation delivery to the upper respiratory tract with little alveolar deposition in the lungs.

Effectiveness of the PRECEDE-PROCEED model for improving the care knowledge, skill, and sense of competence in mothers of preterm infants.

OBJECTIVE: This quasi-randomized controlled trial was performed to evaluate the effects of the PRECEDE-PROCEED model (PPM) in enabling mothers of preterm infants to develop care knowledge, skill, and a sense of competence. METHODS: Among 116 mothers of preterm infants, 60 received traditional discharge education (control group) and 56 received PPM discharge education (PPM group). Improvement in knowledge and skills was transformed into the mothers' routine daily care of infants. The primary outcome was knowledge of preterm infant care. The secondary outcomes were preterm infant care skills and a sense of competence, routine intervention compliance among mothers, and the readmission rate of infants 6 months after discharge. RESULTS: Six months after discharge, the mean knowledge score and mean skills score were significantly higher in the PPM group than in the control group. The mothers' sense of competence with respect to both self-efficacy and satisfaction was also significantly better in the PPM group than in the control group. Moreover, intervention behavior compliance and the readmission rate were significantly better in the PPM group than in the control group. CONCLUSION: Care knowledge, skills, and sense of competence in mothers of preterm infants improved after implementation of the PPM.

Efficient capture and stabilization of iodine via gas-solid reaction using cyclodextrin metal-organic frameworks.

For treatment of wound infection with stabilized iodine, potassium iodide cyclodextrin metal-organic frameworks (KI-CD-MOF) was prepared to carry iodine via gas-solid reaction. Apart from highly ordered porous frameworks, KI-CD-MOF contains uniformly distributed iodide ions which stabilize iodine (I2). X-ray photoelectron spectroscopy and potentiometric titration were utilized to confirm the formation of I3- in the highly porous KI-CD-MOF as I2@KI-CD-MOF. Molecular simulation and characterizations of the synchrotron radiation Fourier transform infrared spectroscopy, differential scanning calorimeter, powder X-ray diffraction and N2 adsorption were conducted to illustrate the inclusion mechanism of iodine in I2@KI-CD-MOF. The apparent solubility of iodine in water was 3.86 times enhanced. The stability and antibacterial activity tests demonstrated that the highly-dispersed iodide ions in KI-CD-MOF are crucial in improvement to the solubility, stability, and bacteriostatic effects of active iodide. Therefore, KI-CD-MOF has broad application prospects and advantages in efficiently capturing and stabilizing iodine.

[Analysis of the Urban Water Eco-environment Protection Strategy in the Beijing-Tianjin-Hebei Region from "Three Waters" Overall Planning].

Clarifying the direction and strategy of water eco-environment protection in the Beijing-Tianjin-Hebei region is of great significance for realizing the water eco-environment protection and high-quality, coordinated development of the Beijing-Tianjin-Hebei area, as well as the goal of building a beautiful China by 2035. From the perspective of "Three Waters" overall planning, based on the urban scale of the Beijing-Tianjin-Hebei region, this study constructed six dimensions of water resources, water environment, water ecology (Three Waters), socio-economic development level, pollutant emissions, and environmental governance efforts. The water eco-environment protection strategy analysis system provided a logical framework for quantifying the current status of the water eco-environment. The ideal value was compared in each city, the PROMETHEE method was used to quantify the gap between each city and the ideal value of water eco-environment protection, and the current situation of the water eco-environment in Beijing-Tianjin-Hebei cities was evaluated. Additionally, water eco-environment protection strategies were formulated according to local conditions. The ranking of the comprehensive level of water eco-environment protection from high to low was Beijing>Tianjin>Qinhuangdao>Hengshui>Zhangjiakou>Langfang>the mean value of net flow value (Phi)>Handan>Chengde>Cangzhou>Baoding>Tangshan>Shijiazhuang>Xingtai; a large gap remained between the level and the ideal value. The hierarchical analysis showed that the advantages and disadvantages of each city's water eco-environment protection were different from dimensions to indicators, and they had the characteristics of local water eco-environment protection. Future efforts should determine the water ecological, environmental protection indicator level of each city in the Beijing-Tianjin-Hebei region, conduct a separate analysis for each city, and propose protection strategies for future development, as well as continue to help the water eco-environmental protection in the Beijing-Tianjin-Hebei region.

Hydrogen peroxide responsive covalent cyclodextrin framework for targeted therapy of inflammatory bowel disease.

The incidence and prevalence of inflammatory bowel disease (IBD) are steadily rising worldwide, where the pathogenesis and progression are intrinsically connected to oxidative stress and irregular high levels of reactive oxygen species. To achieve effective therapy for IBD, using hydrogen peroxide (H2O2)-activatable antioxidant prodrug (BRAP) as a linker to crosslink cyclodextrin metal-organic framework, a novel H2O2 responsive covalent cyclodextrin framework (defined as BCOF) was formulated. BCOF featured excellent ROS-responsive hydrolysis and therapeutic p-hydroxybenzyl alcohol released in a H2O2 concentration dependent manner in vitro. Furthermore, BCOF demonstrated 5 times greater retention in the inflamed colon compared to the normal colon in vivo following oral administration. Most importantly, BCOF improved the viability of RAW264.7 cells from H2O2-induced damage in vitro and alleviated the deterioration of IBD with reduced symptoms of inflammation in vivo. In conclusion, our findings suggest that BCOF deserve further consideration as a potential therapeutic nanomedicine for IBD treatment.

Co-composting of fresh tobacco leaves and soil: an exploration on the utilization of fresh tobacco waste in farmland.

A large amount of fresh tobacco waste with high water content are produced in farmland, and it may cause environmental pollution if it is not properly treated. The fresh tobacco waste is not easily collected and transported, resulting in its centralized treatment is expensive. This study is to clarify whether it is feasible to treat fresh tobacco wastes by co-composting of them and soil in farmland and applied the obtained compost product into the soil instead of a part of tobacco-specific fertilizer. The results showed that, compared with that in original soil, the relative abundance of Pseudomonas, Azotobacter, and Coprinus of the co-composted products increased by roughly 244%, 323%, and 675%, respectively, and effective nitrogen and available potassium increased by roughly 157% and 132%, respectively. In addition, the nicotine content in co-composted products decreased dramatically compared with the discarded tobacco leaves. The application of the co-composted products and 20% fertilizer amount (15 g/plant) (YD5) exhibited the highest relative abundance of beneficial microbial communities in the soil and the best growth of tobacco plants. The co-composting of fresh tobacco waste and soil in farmland is an effective measure to treat the fresh tobacco waste, and its products increased beneficial microorganisms and stimulate the growth of tobacco plants by replacing an amount of the fertilizer.

Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks.

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The in vitro release profiles of STV from STV@CD-MOF (0.5:1) were pH-independent in distinct pH media and closed to be thoroughly released but no such release profiles were observed for STV@CD-MOF (1:1) owing to nanoclusters formation. The bioavailability of STV@CD-MOF (1:1) in rats was 8.67-fold higher than that of STV, and was 1.32- and 1.27-fold higher than that of STV@CD and STV@CD-MOF (0.5:1). Our results indicated that the inclusion mechanism played a primary role when STV in CD-MOF was at a low loading ratio, while the increasement in bioavailability at a high loading ratio, which was attributed to the nanocluster mechanism. This was confirmed by molecular simulation. In conclusion, CD-MOF is a promising system for STV loading, overcoming the insolubility and to improve the bioavailability of this natural compound.

Effects of cefuroxime axetil combined with Xingpi Yanger granules on the serum gastrin, motilin, and somatostatin levels in children with upper respiratory tract infection accompanied by diarrhea: results of a randomized trial.

BACKGROUND: The purpose of the study was to investigate the effects of cefuroxime axetil combined with Xingpi Yanger granules on the treatment of upper respiratory tract infection accompanied by diarrhea and on serum gastrin (GAS), motilin (MOT), and somatostatin (SS) levels in children. METHODS: In total, 124 children with upper respiratory tract infection accompanied by diarrhea admitted to the department of pediatrics in our hospital from May 2019 to May 2020 were selected and divided into a study group (n=62) and a reference group (n=62), according to admission number. The reference group children received routine treatment, while the children in the study group were treated with cefuroxime axetil combined with Xingpi Yanger granules. After treatment, each clinical index of the children in both groups was detected to evaluate the clinical efficacy of the different treatment methods. RESULTS: There were no significant differences in gender ratio, average age, mean body temperature, mean duration of diarrhea, average weight, or place of residence between the 2 groups (P>0.05); the total clinical effective rate after treatment in the study group was significantly higher than that in the reference group (P<0.05); the dehydration correction time, antipyretic time, antidiarrheal time, and total treatment time in the study group were all significantly lower than those in the reference group (P<0.001); the serum GAS and MOT levels at T1, T2, and T3 in the study group were significantly lower than those in the reference group (P<0.001), whereas the SS levels at T1, T2, and T3 in the study group were significantly higher than those in the reference group (P<0.001); and the incidence of adverse reactions of the children in the study group was significantly lower than that in the reference group (P<0.05). CONCLUSIONS: Cefuroxime axetil combined with Xingpi Yanger granules can significantly lower serum GAS, MOT, and SS levels and shorten treatment time in children with upper respiratory tract infection accompanied by diarrhea, with significant clinical efficacy and high safety, and is thus worthy of application and promotion. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100049234.

Solidification of volatile D-Limonene by cyclodextrin metal-organic framework for pulmonary delivery via dry powder inhalers: In vitro and in vivo evaluation.

D-Limonene (D-Lim), a volatile oil extracted from citrus fruits, has therapeutic effects on lung inflammation and cancer, whilst the deep delivery of D-Lim was challenging due to its physical instability for a long period of time. To prevent the volatilization of D-Lim and achieve efficient pulmonary delivery, herein, D-Lim was loaded into biodegradable γ-cyclodextrin metal-organic framework (γ-CD-MOF) with optimal loading efficiency achieving 13.79 ± 0.01% (molar ratio of D-Lim and γ-CD-MOF was 1.6:1), which possessed cubic shape with controllable particle size (1-5 µm). The experimental results indicated that γ-CD-MOF could improve the stability of D-Lim. A series of characterizations and molecular docking were used to reveal the interaction between D-Lim and γ-CD-MOF. The solidification of D-Lim by γ-CD-MOF played a crucial role in the exploitation of its inhalable dosage form, dry powder inhaler (DPI). Specifically, the aerosolization of D-Lim@γ-CD-MOF for inhalation was satisfactory with a fine particle fraction (FPF) of 33.12 ± 1.50% at 65 L/min of flow rate. Furthermore, in vivo study had shown a 2.23-fold increase in bioavailability of D-Lim solidified by γ-CD-MOF for inhalation compared to D-Lim for oral administration. Therefore, it is considered that γ-CD-MOF could be an excellent carrier for pulmonary drug delivery to realize solidification and lung therapeutic effects of volatile oils.

Controlled release of iodine from cross-linked cyclodextrin metal-organic frameworks for prolonged periodontal pocket therapy.

Effective therapeutic system to periodontitis was designed using cross-linked cyclodextrin metal-organic framework (COF) as carrier for iodine and further suspended in hydroxyethyl cellulose gel as I2@COF-HEC hydrogel. Inclusion of iodine within the COF was demonstrated by SR-FTIR spectral and characteristic DSC and TGA changes. Molecular modelling identified the interaction of iodine with both COF central cavity and individual cyclodextrin moieties of COF. In vitro results of study demonstrated that iodine release in artificial saliva from I2@COF-HEC hydrogel could be extended up to 5 days, which was slower than I2@COF particles. Using an in vivo rat model of periodontitis, micro-computed tomography of alveolar bone morphology demonstrated that I2@COF-HEC hydrogel showed similar effects in decreasing periodontal pocket depth and alveolar bone resorption to minocycline ointment, a periodontitis antibiotic. The I2@COF-HEC hydrogel is a novel local delivery device of iodine as a broad spectrum antimicrobial use for treatment of periodontitis.

Multiscale Co-reconstruction of Lung Architectures and Inhalable Materials Spatial Distribution.

The effective pulmonary deposition of inhaled particulate carriers loaded with drugs is a prerequisite for therapeutic effects of drug delivery via inhalation route. Revealing the sophisticated lung scaffold and intrapulmonary distribution of particles at three-dimensional (3D), in-situ, and single-particle level remains a fundamental and critical challenge for dry powder inhalation in pre-clinical research. Here, taking advantage of the micro optical sectioning tomography system, the high-precision cross-scale visualization of entire lung anatomy is obtained. Then, co-localized lung-wide datasets of both cyto-architectures and fluorescent particles are collected at full scale with the resolution down to individual particles. The precise spatial distribution pattern reveals the region-specific distribution and structure-associated deposition of the inhalable particles in lungs, which is undetected by previous methods. Overall, this research delivers comprehensive and high-resolution 3D detection of pulmonary drug delivery vectors and provides a novel strategy to evaluate materials distribution for drug delivery.

ß-Cyclodextrin-grafted hyaluronic acid as a supramolecular polysaccharide carrier for cell-targeted drug delivery.

ß-Cyclodextrin (ß-CD) was grafted onto hyaluronic acid (HA) in a single step to generate a supramolecular biopolymer (HA-ß-CD) that was explored for targeted drug delivery applications. Along with its excellent biocompatibility, the prepared HA-ß-CD exhibits not only exceptionally high loading capacity for the model drugs doxorubicin and Rhodamine B through the formation of inclusion complexes with the ß-CD component, but also the capability of targeted drug delivery to cancerous cells with a high level of expression of CD44 receptors, attributable to its HA component. The polymer can release the drug under slightly acidic conditions. With all its attributes, HA-ß-CD may be a promising cancer-cell-targeting drug carrier.

Mechanism and optimization of supramolecular complexation-enhanced fluorescence spectroscopy for the determination of SN-38 in plasma and cells.

Quantitative detection of two different forms of SN-38 in biological samples is, currently, cumbersome and difficult. A revisit to the mechanism of supramolecular complexation-enhanced fluorescence spectroscopy helps to optimize the determination of SN-38 in plasma and the cellular pharmacokinetics in A549 cells based on the supramolecular complexation. Firstly, the inclusion mechanism dominated by thermodynamic constants was determined by measuring kinetic/thermodynamic parameters (kon , koff , ΔG, ΔH, ΔS). On this basis, the best effect of fluorescence sensitization was optimized through screening the interaction conditions (cyclodextrin species and concentrations, drug levels, temperature, pH of the buffer, and reaction time). Furthermore, the proportional relationship between the concentration of the inclusion complex and the fluorescence intensity was confirmed. Finally, a highly sensitive, selective spectrofluorimetric method was established and validated for quantitative analysis of the lactone and carboxylate molecular states of SN-38 plasma levels in rats and cell membrane transfer kinetics in A549 cell lines. The limits of detection for the lactone and carboxylate forms in plasma were found to be 0.44 ng·ml-1 and 0.28 ng·ml-1 , respectively. Precision and accuracy met the requirements of biological samples analysis. The proposed detection method provided a reference for elucidating the biodistribution of SN-38.

Evaluating the efficacy and safety of bromhexine hydrochloride tablets in treating pediatric COVID-19: A protocol for meta-analysis and systematic review.

BACKGROUND: Bromhexine hydrochloride tablets may be effective in the treatment of Coronavirus disease 2019 (COVID-19) in children. This study will further evaluate the efficacy and safety of bromhexine hydrochloride tablets in the treatment of COVID-19 in children. METHODS: The following electronic databases will be searched, with all relevant randomized controlled trials (RCTs) up to August 2020 to be included: PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), the Chongqing VIP China Science and Technology Database (VIP), Wanfang, the Technology Periodical Database, and the Chinese Biomedical Literature Database (CBM). As well as the above, Baidu, the International Clinical Trials Registry Platform (ICTRP), Google Scholar, and the Chinese Clinical Trial Registry (ChiCTR) will also be searched to obtain more comprehensive data. Besides, the references of the included literature will also be traced to supplement our search results and to obtain all relevant literature. RESULTS: This systematic review will evaluate the current status of bromhexine hydrochloride in the treatment of COVID-19 in children, to evaluate its efficacy and safety. CONCLUSION: This study will provide the latest evidence for evaluating the efficacy and safety of bromhexine hydrochloride in the treatment of COVID-19 in children. PROSPERO REGISTRATION NUMBER: CRD42020199805. ETHICS AND DISSEMINATION: The private information of individuals will not be published. This systematic review will also not involve endangering participant rights. Ethical approval is not available. The results may be published in peer-reviewed journals or disseminated at relevant conferences.

Paeonol loaded cyclodextrin metal-organic framework particles for treatment of acute lung injury via inhalation.

Administration of drugs via inhalation can overcome issues related to poor water solubility, low absorption or bioavailability associated with oral administration. In the current study we used γ-cyclodextrin metal organic frameworks (CD-MOFs) - of inhalable particle sizes, with cubic morphologies and favorable aerodynamic properties to achieve targeted pulmonary drug delivery via dry powder inhalers. The active natural compound, paeonol (PAE), was chosen as a model drug for treatment of acute lung injury (ALI). After loading of PAE into CD-MOF particles of inhalable sizes, PAE was rapidly released in phosphate buffer (pH = 7.4; 90% within 30 min) and in vivo experiments. After mixing with coarse and fine lactose (Inhalac®230: Inhalac®400: PAE-CD-MOF = 40:10:50, w/w/w), paeonol had a high fine particle fraction (FPF) (28.59%). Atom force microscopy was used to assess surface roughness and adhesive force. In vivo inhalation of PAE-CD-MOF dry powder inhaler by rat demonstrated rapid absorption (tmax of 4.0 min) and high absolute bioavailability (71%) of PAE, highlighting significant improvements in absorption and bioavailability of PAE when compared with oral administration (Cmax and absolute bioavailability increased 6.5 and 9.3 folds, respectively). Results of in vivo experiments were consistent with cellular permeability studies (after loading into CD-MOF, the permeability of PAE improved about 5 folds in comparison to the pure PAE). Finally, the efficacy of inhaled PAE for ALI was validated by histopathological examination and via reduced levels of inflammatory factors observed in rat plasma. Overall, targeted pulmonary delivery of paeonol by inhaled PAE-CD-MOF particles appears to be promising method of delivery for treatment of ALI.

Hyaluronic-acid-based ß-cyclodextrin grafted copolymers as biocompatible supramolecular hosts to enhance the water solubility of tocopherol.

Hyaluronic acid (HA), a common biopolymer found in the extracellular fluid, was grafted with ß-cyclodextrin (ß-CD) to form a composite polymer that could form inclusion complexes with tocopherol (VE), enhancing its water-solubility and serving as a model drug delivery system. Herein, different copolymers were prepared with varying HA:ß-CD ratios and characterized. VE loading capacity was directly correlated with increased ß-CD composition in the polymers and morphological changes were observed upon VE binding. The host materials and their VE inclusion complexes are not cytotoxic, and are thus useful for VE and drug delivery.