Manganese Dioxide Nanoplatform with a Hollow Rhombic Dodecahedron Morphology for Drug Delivery.

Manganese dioxide (MnO2) is considered as a promising drug carrier material suitable for the tumor microenvironment while lacking conducive structures for drug loading. Herein, we construct a MnO2 nanoplatform with a hollow rhombic dodecahedral morphology for drug delivery. In this work, we obtained zeolitic imidazolate framework nanoparticles (ZIF-90 NPs) via a coordination reaction. Furthermore, the drug-loading nanoparticles (ZIF-90/DOX NPs) were obtained by Schiff's base reaction and then selected as a sacrificial template to obtain the hollow nanoplatforms (ZIF-90@MnO2 NPs). Moreover, the photothermal effect and multiresponsive drug release behaviors were revealed by loading the photothermal agent IR-820 and the anticancer drug doxorubicin hydrochloride (DOX). Our study demonstrates that the ZIF-90@MnO2 NPs loaded with photosensitizers exhibited excellent photothermal conversion performance. Benefiting from the hollow structure and redox activity, remarkable drug loading and release performances of ZIF-90@MnO2 NPs were achieved. It is shown that ZIF-90@MnO2 NPs achieved a satisfactory drug-loading efficiency (up to ca. 69.7%) for DOX. More promisingly, the ZIF-90@MnO2 NPs exhibited significant glutathione (GSH)/pH-responsive drug release and degradation performances. Overall, this work highlights the potential of controlled drug release of nanocarriers and offers unique insights into the design of nanocarriers with hollow structures.

Novel Injectable, Self-Healing, Long-Effective Bacteriostatic, and Healed-Promoting Hydrogel Wound Dressing and Controlled Drug Delivery Mechanisms.

Multivalent ion cross-linking has been used to form hydrogels between sodium alginate (SA) and hyaluronic acid (HA) in previous studies. However, more stable and robust covalent cross-linking is rarely reported. Herein, we present a facile approach to fabricate a SA and HA hydrogel for wound dressings with injectable, good biocompatibility, and high ductility. HA was first reacted with ethylenediamine to graft an amino group. Then, it was cross-linked with oxidized SA with dialdehyde to form hydrogel networks. The dressing can effectively promote cell migration and wound healing. To increase the antibacterial property of the dressing, we successfully loaded tetracycline hydrochloride into the hydrogel as a model drug. The drug can be released slowly in the alkaline environment of chronic wounds, and the hydrogel releases drugs again in the more acidic environment with wound healing, achieving a long-term antibacterial effect. In addition, one-dimensional partial differential equations based on Fickian diffusion with time-varying diffusion coefficients and hydrogel thicknesses were used to model the entire complex drug release process and to predict drug release.

A Self-Assembly-Induced Exciton Delocalization Strategy for Converting a Perylene Diimide Derivative from a Type-II to Type-I Photosensitizer.

Type-I photosensitizers have shown advantages in addressing the shortcomings of traditional oxygen-dependent type-II photosensitizers for the photodynamic therapy (PDT) of hypoxic tumors. However, developing type-I photosensitizers is yet a huge challenge because the type-II energy transfer process is much faster than the type-I electron transfer process. Herein, from the fundamental point of view, an effective approach is proposed to improve the electron transfer efficiency of the photosensitizer by lowering the internal reorganization energy and exciton binding energy via self-assembly-induced exciton delocalization. An example proof is presented by the design of a perylene diimide (PDI)-based photosensitizer (PDIMp) that can generate singlet oxygen (1O2) via a type-II energy transfer process in the monomeric state, but induce the generation of superoxide anion (O2˙-) via a type-I electron transfer process in the aggregated state. Significantly, with the addition ofcucurbit[6]uril (CB[6]), the self-assembled PDIMp can convert back to the monomeric state via host-guest complexation and consequently recover the generation of 1O2. The biological evaluations reveal that supramolecular nanoparticles (PDIMp-NPs) derived from PDIMp show superior phototherapeutic performance via synergistic type-I PDT and mild photothermal therapy (PTT) against cancer under either normoxia or hypoxia conditions.

A novel theoretical strategy for predicting dissolution kinetics and mechanisms of pharmaceuticals in complex biorelevant media.

The influence mechanism of biorelevant media on the dissolution of active pharmaceutical ingredients (APIs) is the key to their formulation design. The dissolution kinetics of naproxen (NAP) and indomethacin (IND) in biorelevant media was systematically investigated. The dissolution mechanism was analyzed by chemical potential gradient model to explore the influence of surfactant type, pH and ionic strength. Hexadecyl trimethyl ammonium bromide (CTAB) is superior to sodium dodecyl sulfate (SDS) in promoting the dissolution of NAP and IND by increasing the solubility and accelerating the surface reaction processes. The electrostatic repulsion between SDS and NAP and IND with the same negative charge facilitates the diffusion of API, while the mutual attraction between CTAB and NAP and IND is not conducive to diffusion. High pH was favorable for the dissolution of acidic NAP and IND, as the simultaneous increase in solubility, surface reaction constant, and diffusion constant. High ionic strength was beneficial for the surface reaction of NAP and IND, but hindered their diffusion. It was shown that the modeling results were in conformity with the in vitro experimental data. These results are expected to provide theoretical supports for the design of biorelevant media and pharmaceutical formulations in the pharmaceutical development.

Prediction of enhanced drug solubility related to clathrate compositions and operating conditions: Machine learning study.

Although complexation technique has been documented as a promising strategy to enhance the dissolution rate and bioavailability of water-insoluble drugs, prediction of the enhanced drug solubility related to clathrate compositions and operating conditions is still a challenge. Herein, clathrate compositions (drug content (DC), drug molecular weight (M) and molar ratio (Ratio)), operating conditions (drug concentration (C), pH, pressure (P), temperature (T) and dissolution time (t)) under the different excipients (PEG, PVP, HPMC and cyclodextrin) as main solubilizers of the clathrates condition as input parameters were used to predict two indexes (drug dissolved percentage and dissolution efficiency) simultaneously through machine learning methodfor the first time. The results show that PVP as the main solubilizer of clathrates had higher prediction accuracy to the drug dissolved percentage, and HPMC as the main solubilizer of clathrates had higher prediction accuracy to the drug dissolution efficiency. In addition, the influence of various factors and interactions on the target variables were analyzed. This study affords achievable hints to the quantitative prediction of the drug solubility affected by various compositions and different operating conditions.

Theoretical study on the solvation mechanism of camptothecin in ionic liquids.

To reduce the environmental pollution caused by organic solvents and improve the extraction efficiency, a range of imidazolium-based ionic liquid (IL) combinations of [Omim]+ paired with [Br]-, [BF4]-, [Cl]-, [ClO4]-, [HsO4]-, [NO3]-, [NTf2]-, [OAc]-, [PF6]-, and [TsO]- are explored for the extraction of camptothecin (CPT) using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. It is found that the ILs containing [Br]-, [OAc]-, and [TsO]- anions are the most promising solvents for CPT solvation because they exhibit stronger interaction energy and the lowest self-diffusion coefficient of CPT among all ILs. The microscopic mechanism at the molecular level is revealed based on DFT calculations and MD simulations, and the results demonstrate that the IL (i.e., [Omim][TsO]) containing anions with strong hydrogen bond (HB) acceptability and aromatic ring structure corresponds to both the strongest van der Waals interaction and strongest HB interaction of CPT-anions. Therefore, it is recommended that anions with aromatic ring structures or strong HB acceptability are promising anion candidates, while anions containing electron withdrawing groups and bulky substituents should be avoided. This work provides intermolecular insight into designing and selecting effective ILs for natural insoluble active pharmaceutical ingredient dissolution and extraction in further research.

A novel manganese dioxide-based drug delivery strategy via in situ coating γ-polyglutamic acid/cisplatin for intelligent anticancer therapy.

Cisplatin (CDDP) is one of the most frequently used chemotherapeutic drugs due to its broad-spectrum and potent antitumor activity. Unfortunately, inactivation due to glutathione (GSH) substances and insufficient cellular uptake of CDDP greatly hinder its clinical applications. Herein, manganese dioxide (MnO2) was reported as an efficient glutathione (GSH) consumption material for promoting the accumulation and preventing premature leakage of CDDP in tumor cells. In this work, γ-polyglutamic acid/cisplatin (PGA/CDDP) conjugates and PGA/CDDP nanoparticles (NPs) were respectively constructed via the ligand exchange reaction and electrostatic interaction. Furthermore, PGA/CDDP NPs were in situ coated with MnO2 (PGA/CDDP@MnO2 NPs) through the redox reaction of the residual carboxyl group (-COOH) and potassium permanganate (KMnO4). As a result, the PGA/CDDP@MnO2 NPs achieved a satisfactory drug-loading efficiency (ca. 37.26%) and multi-responsive controlled drug release. Remarkably, the MnO2 shells exhibited excellent performance for efficient glutathione (GSH) consumption and significantly enhanced the killing effect (ca. 2-3 times) in human lung cancer cells (A549) compared with pure CDDP. Moreover, it was observed that PGA/CDDP@MnO2 NPs could also inhibit the migration and invasion of A549 cells. Overall, these remarkable performances of PGA/CDDP@MnO2 NPs make MnO2 promising for controlled drug release and intelligent anticancer therapy.

FC-BBR/IND-induced glucose oxidase nanodrugs for targeted combination therapy.

Targeted therapy from cells to mitochondria can improve the bioavailability and therapeutic effects of drugs. Combination therapy by combining two or more therapeutic methods comes to be seen a hopeful strategy to overcome the emergence of resistance. Ferrocene (FC) derivatives of the sandwich structure can not only directly inhibit the proliferation of cancer cells but also catalyze the Fenton reaction to enhance chemodynamic therapy. Berberine (BBR) is a Chinese herbal extract with mitochondria-targeted anticancer activity. In our work, glucose oxidase (GOD) was induced to self-assemble by ferrocene-berberine conjugate (FC-BBR) and indomethacin (IND), which was then encapsulated by hyaluronic acid (HA) and formed nanodrugs (FC-BBR/IND@GOD@HA NPs). Molecular simulation results showed that the drugs could be bound to multiple sites of GOD and induce its self-assembly. The prepared nanoassembly could inhibit the proliferation and induce the apoptosis of HepG2 cells, which might be the result of targeted chemodynamic therapy and starvation therapy. Moreover, the FC-BBR/IND@GOD@HA NPs could also promote the production of reactive oxygen species and the loss of mitochondrial membrane potential and block the cells in S phase. More importantly, it could inhibit the movement and migration of cancer cells, which gave it the potential to prevent tumor metastasis.

Thermosensitive hydrogel-functionalized gold nanorod/mesoporous MnO2 nanoparticles for tumor cell-triggered drug delivery.

MnO2 owns distinct redox, imaging, and degradable properties corresponding to the tumor microenvironment. However, the onefold structure and non-modifiable property cause many obstacles to anticancer applications. In this report, we first prepared a typical core-shell gold nanorod (GNR)/manganese dioxide (MnO2) nanoparticles (GNR/MnO2 NPs). Interestingly, the MnO2 had a mesoporous channel and modifiable hydroxyl group (OH). Here, the unique 'OH' groups were modified and further grafted with poly(N-isopropylacrylamide-co-acrylic acid) (PNA). As a dual-sensitive hydrogel, it was selected as the thermal/pH-sensitive component in the hybrid nanoparticles (GNR/MnO2/PNA NPs). The anticancer drug doxorubicin hydrochloride (DOX) was selected and loaded into the hybrid nanoparticles (GNR/MnO2/PNA-DOX NPs). The GNR/MnO2/PNA NPs achieved satisfying drug-loading efficiency and glutathione (GSH)/pH/thermal-responsive drug-controlled release. As a side benefit, the GNR/MnO2/PNA NPs showed potential as excellent near-infrared (NIR)-excited nanoplatforms for photothermal therapy (PTT). Delightedly, the studies demonstrated that the GNR/MnO2/PNA-DOX NPs showed a noticeable killing effect on tumor cells, whether it is tumor cell-triggered drug release or photothermal effect. Besides, it not only could enhance mitochondrial damage but also could inhibit the migration and invasion of tumor cells. Quite the reverse, it had little negative impact on normal cells. The feature can prevent anticancer drugs and nanoparticles from killing normal cells. Consequently, GNR/MnO2/PNA NPs have potential applications in drug delivery and synergistic therapy due to these advantageous features.

Integrated computer-aided formulation design: A case study of andrographolide/ cyclodextrin ternary formulation.

Current formulation development strongly relies on trial-and-error experiments in the laboratory by pharmaceutical scientists, which is time-consuming, high cost and waste materials. This research aims to integrate various computational tools, including machine learning, molecular dynamic simulation and physiologically based absorption modeling (PBAM), to enhance andrographolide (AG) /cyclodextrins (CDs) formulation design. The lightGBM prediction model we built before was utilized to predict AG/CDs inclusion's binding free energy. AG/γ-CD inclusion complexes showed the strongest binding affinity, which was experimentally validated by the phase solubility study. The molecular dynamic simulation was used to investigate the inclusion mechanism between AG and γ-CD, which was experimentally characterized by DSC, FTIR and NMR techniques. PBAM was applied to simulate the in vivo behavior of the formulations, which were validated by cell and animal experiments. Cell experiments revealed that the presence of D-α-Tocopherol polyethylene glycol succinate (TPGS) significantly increased the intracellular uptake of AG in MDCK-MDR1 cells and the absorptive transport of AG in MDCK-MDR1 monolayers. The relative bioavailability of the AG-CD-TPGS ternary system in rats was increased to 2.6-fold and 1.59-fold compared with crude AG and commercial dropping pills, respectively. In conclusion, this is the first time to integrate various computational tools to develop a new AG-CD-TPGS ternary formulation with significant improvement of aqueous solubility, dissolution rate and bioavailability. The integrated computational tool is a novel and robust methodology to facilitate pharmaceutical formulation design.

Van der Waals force-driven indomethacin-ss-paclitaxel nanodrugs for reversing multidrug resistance and enhancing NSCLC therapy.

The high expression of multidrug resistance-associated protein 1 (MRP1) in cancer cells caused serious multidrug resistance (MDR), which limited the effectiveness of paclitaxel (PTX) in non-small cell lung cancer (NSCLC) chemotherapy. Indomethacin (IND), a kind of non-steroidal anti-inflammatory drugs (NSAIDs), which has been confirmed to be a potential MRP1 inhibitor. Taking into account the advantages of old drugs without extra controversial biosafety issue, in this manuscript, the disulfide bond (-S-S-) was employed for connecting IND and PTX to construct conjugate IND-S-S-PTX, which was further self-assembled and formed nanodrug (IND-S-S-PTX NPs). The particle size of IND-S-S-PTX NPs was ~160 nm with a narrow PDI value of 0.099, which distributed well in water and also exhibited a stable characteristic. Moreover, due to the existence of disulfide bond, the NPs were sensitive to the high level of glutathione (GSH) in tumor microenvironment. Molecular dynamics (MD) simulation presented the process of self-assembly in detail. Density functional theory (DFT) calculations revealed that the main driving force in self-assembly process was originated from the van der waals force. In addition, this carrier-free nano drug delivery systems (nDDs) could reverse the MDR by downregulating the expression of MRP1 protein in A549/taxol.

Facile modification of hydrochar derived from cotton straw with excellent sorption performance for antibiotics: Coupling DFT simulations with experiments.

This study aimed to investigate the sorption of tetracycline (TC) and norfloxacin (NOR) by modified cotton straw hydrochars (CSHC), which would enable the agricultural waste to be processed and recycled. Three kinds of hydrochars were prepared by H2SO4, KOH and KMnO4 modification, showed obvious differences in structures and surface functional groups. The sorption processes contain film diffusion, intraparticle diffusion, and equilibrium. The interaction mechanism between hydrochar and antibiotics include π-π stacking, hydrogen bond, and electrostatic interaction. KMnO4-modified hydrochar had the largest sorption capacity for TC (58.09 mg/g), while H2SO4-modified hydrochar had the largest sorption capacity for NOR (49.64 mg/g). Density functional calculations (DFT) results confirmed that the sorption capacity between hydrochar (HC) and TC was larger than that between HC and NOR. During the sorption process, the TC and NOR were regarded as electron acceptor and electron donor. Generally, CSHC-KMnO4 and CSHC-H2SO4 may be simply prepared and have the potential to eliminate antibiotics from water.

Nanostructured manganese dioxide for anticancer applications: preparation, diagnosis, and therapy.

Nanostructured manganese dioxide (MnO2) has attracted extensive attention in the field of anticancer applications. As we all know, the tumor microenvironment is usually characterized by a high glutathione (GSH) concentration, overproduced hydrogen peroxide (H2O2), acidity, and hypoxia, which affect the efficacy of many traditional treatments such as chemotherapy, radiotherapy, and surgery. Fortunately, as one kind of redox-active nanomaterial, nanostructured MnO2 has many excellent properties such as strong oxidation ability, excellent catalytic activity, and good biodegradability. It can be used effectively in diagnosis and treatment when it reacts with some harmful substances in the tumor site. It can not only enhance the therapeutic effect but also adjust the tumor microenvironment. Therefore, it is necessary to present the recent achievements and progression of nanostructured MnO2 for anticancer applications, including preparation methods, diagnosis, and treatment. Special attention was paid to photodynamic therapy (PDT), bioimaging and cancer diagnosis (BCD), and drug delivery systems (DDS). This review is expected to provide helpful guidance on further research of nanostructured MnO2 for anticancer applications.

Triple stimuli-responsive supramolecular nanoassembly with mitochondrial targetability for chemophotothermal therapy.

Mitochondria play crucial roles in a variety of cellular physiological processes, mitochondria-accumulating drug delivery has drawn pronounced attention in the field of cancer theranostics. Camptothecin (CPT) is a DNA Topoisomerase I inhibitor and exerts a broad-spectrum anticancer profile. Berberine (BBR) is able to perferably enter into cancer cell mitochondria and trigger the cell apoptosis. In this work, CPT and BBR were combined together (CPT-ss-BBR) through GSH-responsible disulfide bond, and then co-assembled with photosensitizer indocyanine green (ICG) into nanodrugs (CPT-ss-BBR/ICG NPs), which was driven through hydrophobic, π-π stacking and especially, electrostatic interactions of anions and cations as found by molecular dynamics simulations and quantum chemistry calculations. Our developed nanodrugs displayed an average size of ~168 nm and showed exceptional instability by irradiation presence, acid condition and high concentration of GSH, thereby eliciting the rapid disassembly and accelerating drug release. The better therapy effect of CPT-ss-BBR/ICG NPs on A549 cells might be attributed to triply stimuli-responsive rapid disassembly, preferable accumulation into mitochondria and combined chemotherapy and photothermal therapy, all of which directly rendered the notable loss of mitochondria membrane potential, high level of reactive oxygen species in cancer cells, accelerated the apoptosis of cancer cells and repressed the growth of tumors.

The influence of polymeric excipients on desupersaturation profiles of active pharmaceutical ingredients. 1: Polyethylene glycol.

Polymeric excipients have proven to be beneficial in stabilizing supersaturated solutions of poorly soluble active pharmaceutical ingredients (APIs). They are therefore considered an important tool in improving oral bioavailability of such APIs. To better understand this effect, desupersaturation of two model APIs - naproxen and indomethacin- were investigated with up to 1 wt% of polyethylene glycol (PEG) in aqueous solution. A crystal-growth model is proposed that allows simultaneous differentiation between thermodynamic and kinetic effects. It could be revealed that PEG, independent of molecular weight and concentration, acts as a solubilizer, thus increasing the equilibrium solubility of the API and thereby reducing the thermodynamic driving force for crystal growth from supersaturated solutions. In contrast, PEG does not change the kinetic crystal-growth parameters. This theoretical approach allowed predicting the API crystal-growth-dominated desupersaturation profiles in the presence of PEG at different concentrations only using the kinetic crystal-growth parameters determined for polymer-free systems and API solubilities measured in the presence of PEG.

Mitochondria-targeting nanomedicine self-assembled from GSH-responsive paclitaxel-ss-berberine conjugate for synergetic cancer treatment with enhanced cytotoxicity.

Mitochondria play a fundamental role in plenty of cellular metabolic processes, and mitochondria-homing drug delivery is a promising and effective strategy for cancer treatment. Paclitaxel (PTX) is a broad-spectrum anticancer drug, but its therapeutic effect is highly limited due to the development of multidrug resistance. Berberine (BBR) can selectively accumulate in tumor cell mitochondria and inhibit the growth of cancer cells with different biological action mechanism from PTX. Here, these two "old" drug molecules, BBR and PTX were linked together by a disulfide bond rope to construct GSH-responsible drug-drug conjugate (PTX-ss-BBR). Molecular dynamics simulation results revealed that PTX-ss-BBR conjugate could be self-assembled in water to form nanoparticles (PTX-ss-BBR NPs) forced by π-π stacking and hydrophobic interactions and the average size of NPs was around 165 nm measured by DLS. The better in vitro potency of PTX-ss-BBR NPs against A549 cells might be ascribed to the simultaneous drug release and mitochondria-targeting delivery, which dissipated mitochondria membrane potential, upregulated ROS levels in cancer cells, arrested cells in phase G2/M, elicited apoptosis of cancer cells and inhibited the growth of tumors. Furthermore, PTX-ss-BBR NPs also exerted efficacy better than or comparable to BBR on S. aureus and E. coli, which were closely associated with the development of lung cancer. The synergistic effect of PTX and BBR enhanced the treatment effect of conventional chemotherapy drugs against A549 cells.

Insight into the Dissolution Molecular Mechanism of Ternary Solid Dispersions by Combined Experiments and Molecular Simulations.

With the increase concern of solubilization for insoluble drug, ternary solid dispersion (SD) formulations developed more rapidly than binary systems. However, rational formulation design of ternary systems and their dissolution molecular mechanism were still under development. Current research aimed to develop the effective ternary formulations and investigate their molecular mechanism by integrated experimental and modeling techniques. Glipizide (GLI) was selected as the model drug and PEG was used as the solubilizing polymer, while surfactants (e.g., SDS or Tween80) were the third components. SD samples were prepared at different weight ratio by melting method. In the dissolution tests, the solubilization effect of ternary system with very small amount of surfactant (drug/PEG/surfactant 1/1/0.02) was similar with that of binary systems with high polymer ratios (drug/PEG 1/3 and 1/9). The molecular structure of ternary systems was characterized by differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), X-ray diffraction (XRD), and scanning electron microscope (SEM). Moreover, molecular dynamic (MD) simulations mimicked the preparation process of SDs, and molecular motion in solvent revealed the dissolution mechanism of SD. As the Gordon-Taylor equation described, the experimental and calculated values of Tg were compared for ternary and binary systems, which confirmed good miscibility of GLI with other components. In summary, ternary SD systems could significantly decrease the usage of polymers than binary system. Molecular mechanism of dissolution for both binary and ternary solid dispersions was revealed by combined experiments and molecular modeling techniques. Our research provides a novel pathway for the further research of ternary solid dispersion formulations.

RGD-modified polymer and liposome nanovehicles: Recent research progress for drug delivery in cancer therapeutics.

Over the past few decades, as the demand for cancer treatment has increased, more rational treatment options (considering size, mode of administration, biocompatibility, efficacy, etc.) and plenty of specifically active targeted nanovehicles have been developed. Integrin receptors targeting are one of the most frequently used approaches because of its highly expressed in cancer cells. In particular, the arginine-glycine-aspartic acid (RGD) peptide and its derivatives have been widely used as ligands for integrin to increase direct targeting capabilies. Polymers as well as liposomes are commonly used as nanovehicles for drug delivery. A variety of work is focused on the RGD-modified polymer and liposome nanovehicles for cancer therapeutics. The goal of this article is to review the published literature in recent years concerning the RGD-modified liposome and polymer nanovehicles to highlight its successful designs for improving cancer therapy and discuss the current challenges as well as the possible development prospects.

The association between platelet indices and deep surgical site infection after open induction internal fixation for traumatic limb fractures.

OBJECTIVES: Deep surgical site infection (DSSI) is one of the most serious complications after open induction internal fixation (ORIF) for traumatic limb fractures. In this study, we aimed to investigate the diagnostic role of platelet indices (platelet count [PLT], mean platelet volume [MPV], and platelet distribution width [PDW]) in DSSI. PATIENTS AND METHODS: Data obtained between January 2011 and December 2017 in The Affiliated Drum Tower Hospital of Nanjing University Medical School from cases (n=29) with DSSI and fracture control subjects (n=29) matched for age, gender, and fracture type were analyzed. The white blood cell (WBC) count, neutrophil count, neutrophil percentage, and platelet indices from blood samples were compared between case and control groups. In addition, the cutoff value, sensitivity, and specificity were calculated by receiver-operating characteristic (ROC) curves. RESULTS: No significant differences were detected in demographic features, the WBC count, neutrophil count, neutrophil percentage, and MPV values between two groups (P>0.05). The PLT values were significantly higher in the case group than in the control group (303.00±139.27 vs 196.10±59.61 [109/µL], P=0.001). The PDW values of the case and control groups were 11.77±2.71 and 13.19±2.39%, respectively, and were significantly lower in the case group (P=0.001). ROC curve analysis suggested a cutoff point for PLT as 215.50 (109/µL, larger values indicate pathology) for the diagnosis of DSSI with the sensitivity and specificity of 79.3 and 72.4%, respectively. For PDW, the cutoff point was 10.35% (smaller values indicate patients) for the diagnosis of DSSI with the sensitivity and specificity of 37.9 and 96.6%, respectively. CONCLUSION: Our results suggest that PDW combined with PLT can be used as an important additional test for the diagnosis of DSSI after ORIF for traumatic limb fractures, thus reducing the cost and loss of time.

Analysis of the Literature and Patents on Solid Dispersions from 1980 to 2015.

Background: Solid dispersions are an effective formulation technique to improve the solubility, dissolution rate, and bioavailability of water-insoluble drugs for oral delivery. In the last 15 years, increased attention was focused on this technology. There were 23 marketed drugs prepared by solid dispersion techniques. Objective: This study aimed to report the big picture of solid dispersion research from 1980 to 2015. Method: Scientific knowledge mapping tools were used for the qualitative and the quantitative analysis of patents and literature from the time and space dimensions. Results: Western Europe and North America were the major research areas in this field with frequent international cooperation. Moreover, there was a close collaboration between universities and industries, while research collaboration in Asia mainly existed between universities. The model drugs, main excipients, preparation technologies, characterization approaches and the mechanism involved in the formulation of solid dispersions were analyzed via the keyword burst and co-citation cluster techniques. Integrated experimental, theoretical and computational tools were useful techniques for in silico formulation design of the solid dispersions. Conclusions: Our research provided the qualitative and the quantitative analysis of patents and literature of solid dispersions in the last three decades.