Soluble polyvinylpyrrolidone-based microneedles loaded with Sanguis draconis and Salvia miltiorrhiza for treatment of diabetic wound healing.

BACKGROUND: Nowadays, diabetic wound healing remains a crucial challenge due to their protracted and uncertain healing process. Traditional Chinese medicine (TCM) has demonstrated the therapeutic value of Sanguis draconis (SD)-Salvia miltiorrhiza (SMR) Herb Pair in diabetic wound healing. However, new administration modes are urgently needed for their convenient and wide-ranging applications. OBJECTIVE: We propose a soluble polyvinylpyrrolidone-based microneedle patch containing the herbal extracts of SD and SMR (MN-SD@SMR) for diabetic wound healing. METHODS: The herbal extracts of SD and SMR are purification and concentration via traditional lyophilization. SD endowed MN-SD@SMR with functions to improve high glycemic blood environment and migration of keratinocyte and fibroblast cells. RESULTS: SMR in MN-SD@SMR could improve blood flow velocity and microcirculation in the wound area. The effectiveness of transdermal release and mechanical strengths of MN-SD@SMR were verified. CONCLUSION: Integrating the advantages of these purified herbal compositions, we demonstrated that MN-SD@SMR had a positive healing effect on the wounds in vitro and vivo. These results indicate that soluble polyvinylpyrrolidone-based microneedle patch containing the herbal extracts of SD and SMR has a promising application value due to their superior capability to promote diabetic wound healing.

Effect of PVP Molecular Weights on the Synthesis of Ultrasmall Cus Nanoflakes: Synthesis, Properties, and Potential Application for Phototheranostics.

Copper sulfide nanoparticles (CuS) hold tremendous potential for applications in photothermal therapy (PTT) and photoacoustic imaging (PAI). However, the conventional chemical coprecipitation method often leads to particle agglomeration issues. To overcome this challenge, we utilized polyvinylpyrrolidone (PVP) as a stabilizing agent, resulting in the synthesis of small PVP-CuS nanoparticles named PC10, PCK30, and PC40. Our study aimed to investigate how different molecular weights of PVP influence the nanoparticles' crystalline characteristics and essential properties, especially their photoacoustic and photothermal responses. While prior research on PVP-assisted CuS nanoparticles has been conducted, our study delves deeper into this area, providing insights into optical properties. Remarkably, all synthesized nanoparticles exhibited a crystalline structure, were smaller than 10 nm, and featured an absorbance peak at 1020 nm, indicating their robust photoacoustic and photothermal capabilities. Among these nanoparticles, PC10 emerged as the standout performer, displaying superior photoacoustic properties. Our photothermal experiments demonstrated significant temperature increases in all cases, with PC10 achieving an impressive efficiency of 51%. Moreover, cytotoxicity assays revealed the nanoparticles' compatibility with cells, coupled with an enhanced incidence of apoptosis compared to necrosis. These findings underscore the promising potential of PVP-stabilized CuS nanoparticles for advanced cancer theranostics.

Fabrication of biodegradable and antibacterial films of chitosan/polyvinylpyrrolidone containing Eucalyptus citriodora extracts.

The main objective of this work is to develop biodegradable active films through the combination of the extracts with different solvents sourced from Eucalyptus citriodora leaves, with films made of chitosan (Cs) and polyvinylpyrrolidone (PVP). Chromatographic profiling investigations were carried out to examine the antibacterial characteristics of E. citriodora extracts before their direct incorporation into the polymer films. At this point, the potent antimicrobial properties of the phenol compounds and bioactive components demonstrated an antibacterial activity that was particularly noticeable at a hexane resolution. Different morphological characteristics were seen on films made from these solvent extracts, such as Cs/PVP-AE, Cs/PVP-EAE, and Cs/PVP-HE, when scanning electron microscopy was used. Numerous other outcomes of all the interactions between the extract particles and the film were shown by the pores defined by the Cs/PVP film's porous nature. The addition of the extracts, either alone or in combination, greatly enhanced the Cs/NC/PVP films' mechanical characteristics. It has also been shown that adding plant extracts greatly increased the antibacterial activity of these films. These findings reveal that Cs/PVP films loaded with extract may be utilized as more environmentally acceptable substitutes for possible food packaging application by increasing shelf life of food products.

Characterization and bioactivities of coffee husks extract encapsulated with polyvinylpyrrolidone.

Coffee processing generates large amounts of residues of which a portion still has bioactive properties due to their richness in phenolic compounds. This study aimed to obtain a coffee husks extract (CHE) and to encapsulate it (ECHE) with polyvinylpyrrolidone using a one-step procedure of solid dispersion. The extraction and encapsulation yields were 9.1% and 92%, respectively. Thermal analyses revealed that the encapsulation increased the thermal stability of CHE and dynamic light scattering analyses showed a bimodal distribution of size with 81% of the ECHE particles measuring approximately 711 nm. Trigonelline and caffeine were the main alkaloids and quercetin the main phenolic compound in CHE, and the encapsulation tripled quercetin extraction. The total phenolics content and the antioxidant activity of ECHE, assayed with three different procedures, were higher than those of CHE. The antioxidant activity and the bioaccessibility of the phenolic compounds of ECHE were also higher than those of CHE following simulated gastrointestinal digestion (SGID). Both CHE and ECHE were not toxic against Alliumcepa cells and showed similar capacities for inhibiting the pancreatic α-amylase in vitro. After SGID, however, ECHE became a 1.9-times stronger inhibitor of the α-amylase activity in vitro (IC50 = 8.5 mg/mL) when compared to CHE. Kinetic analysis revealed a non-competitive mechanism of inhibition and in silico docking simulation suggests that quercetin could be contributing significantly to the inhibitory action of both ECHE and CHE. In addition, ECHE (400 mg/kg) was able to delay by 50% the increases of blood glucose in vivo after oral administration of starch to rats. This finding shows that ECHE may be a candidate ingredient in dietary supplements used as an adjuvant for the treatment of diabetes.

Formulation, characterization and and evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement.

OBJECTIVE: To prepare aloe-emodin solid dispersion (AE-SD) and determine the metabolic process of AE and AE-SD in vivo. METHODS: AE-SD was prepared viasolvent evaporation or solvent melting using PEG-6000 and PVP-K30 as carriers. Thermogravimetric analysis, X-ray diffraction spectroscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of AE-SD. Optimal prescriptions were screened viathe dissolution degree determination method. Using Phoenix software, AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid dispersion. Acute toxicity was assessed in mice, and the physiological toxicity was used as the determination criterion for toxicity. RESULTS: AE-SD showed that AE existed in the carrier in an amorphous state. Compared with polyethylene glycol, polyvinylpyrrolidone (PVP) inhibited AE crystallization, causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug dispersion. Therefore, it was more suitable as a carrier material for AE-SD. The addition of poloxamer (POL) was more beneficial to the stability of solid dispersions and could reduce the amount of PVP. The dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1：2：2, and its dissolution effect was also optimal. Based on the pharmacokinetic comparison, the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE, the Cmax of AE-SD was greater than that of AE, and t1/2 and mean residence time of AE-SD were less than AE. The results showed that the drug metabolism in AE-SD was better, and the residence time was shorter. The toxicology study showed that both AE and AE-SD had no toxicity. CONCLUSION: This paper established that the solubility of the drug could be increased after preparing a solid dispersion, as demonstrated by in vitro dissolution experiments. In vivo pharmacokinetics studies confirmed that AE-SD could improve the bioavailability of AE in vivo, providing a new concept for the research and development of AE preparations.

Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia.

There is an urgent need for research into effective interventions for pain management to improve patients' life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs' tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.

Development and characterization of films from Campomanesia xanthocarpa and commercial citrus pectins with different degrees of methyl-esterification.

In this study, pectins from commercial citrus and isolated from gabiroba (Campomanesia xanthocarpa) fruits, were obtained with different degrees of methyl-esterification (DM) and applied in the films. The DM ranged from 0 % to 62.5 % and the gradual de-esterification process was confirmed by mono-dimensional analysis (1H NMR). In order to investigate the influence of DM values in pectin film properties, PCP (DM: 62.5 %); PCP-5 (DM: 37.4 %); PCP-15 (DM: 19.1 %), and a fully de-esterified sample PCP-35 (DM: 0 %) were selected. The functional properties of the films clearly showed that the DM and cross-linking process are necessary to obtain a material with water resistance. Furthermore, pectin isolated from the fruits of gabiroba was purified (GW-Na, DM: 51.9 %) and partially de-esterified (GW-Na-5, DM: 37.1 %). These pectins were used, for the first time, in development of films and the physical and mechanical properties were compared with films made with PCP and PCP-5 samples. GW-Na and GW-Na-5 films presented suitable properties, with reduced solubility reduced (57.1 and 26.2 %), high degree of swelling (2.14 and 2.26), low flexibility (18.05 and 6.11 MPa), respectively. High strength and rigidity (99.36 and 1040.9 MPa), for both films (GW-Na and GW-Na-5) were demonstrated, similar to that obtained by analyzed citrus pectin.

Rapid dissolution microneedle based on polyvinyl alcohol/chitosan for local oral anesthesia.

At present, the main clinical methods of oral local anesthesia are direct injection of anesthetic and surface ointment. However, the pain and fear caused by the injection, the discomfort of topical anesthetic creams, and the scour and moist oral environment during the procedure pose great challenges to oral anesthesia. Herein, we designed a Lido-PVP/PVA DMNP microneedle (MN) for oral local anesthesia. The microneedle tip was consisted of Polyvinylpyrrolidone/Polyvinyl alcohol (PVP/PVA), which can quickly dissolve and release the lidocaine hydrochloride (Lido) drug within 5 min to achieve rapid anesthesia. The backing was composed of polyvinyl alcohol/chitosan (PVA/CS), and its excellent adhesion can overcome saliva erosion and anchor firmly to the oral mucosa, significantly improving the utilization rate of drugs, as well as the patient compliance. MNs have good mechanical properties for tissue insertion while possessing high drug loading (3 mg/MNs). Von Frey tests proved that MNs showed a faster and more effective local anesthetic effect (anesthesia takes effect at 5 min) compared to cream (anesthesia takes effect at 30 min). In addition, the excellent biocompatibility and no skin irritation endowed Lido-PVP/PVA DMNP MNs a great potential for oral local anesthesia in the oral cavity.

Functionalization of selenium nanoparticles with olive polyphenols - impact on toxicity and antioxidative activity.

Selenium nanoparticles (SeNPs) represent novel selenium (Se) formulation characterized by improved biocompatibility and a wider therapeutic range in comparison to inorganic Se. The aim of this work was to investigate the possibilities of functionalization of SeNPs with olive pomace extract (OPE), rich in health-promoting polyphenols, and to obtain innovative forms of nutraceuticals. Cytotoxic and antioxidative activities of four types of SeNPs (polyvinylpyrrolidone stabilized (PVP SeNPs), polysorbate stabilized (PS SeNPs), polyvinylpyrrolidone stabilized and functionalized using OPE (f PVP SeNPs) and polysorbate stabilized and functionalized using OPE (f PS SeNPs) were investigated. SeNPs showed lower toxicity on human hepatocellular carcinoma (HepG2) and human colorectal adenocarcinoma (Caco2) cells compared to selenite. Functionalization with polyphenols significantly improved their direct antiradical (f PVP SeNPs: 24.4 ± 1.84 and f PS SeNPs: 30.9 ± 2.47 mg TE/mmol Se) and reducing properties (f PVP SeNPs: 50 ± 3.16 and f PS SeNPs: 53.6 ± 3.22 mg GAE/mmol) compared to non-functionalized SeNPs. The significant impact of tested SeNPs on intracellular antioxidative mechanisms has been observed and it was dependent on both cell type and physico-chemical properties of SeNPs, indicating the complexity of involved mechanisms.

Study on Improving the Performance of Traditional Medicine Extracts with High Drug Loading Based on Co-spray Drying Technology.

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO3) and ammonium bicarbonate (NH4HCO3) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process.

Subcutaneous Rapid Dissolution Microneedle Patch Integrated with CuO2 and Disulfiram for Augmented Antimelanoma Efficacy through Multimodal Synergy of Photothermal Therapy, Chemodynamic Therapy, and Chemotherapy.

Melanoma is a malignancy of the skin that is resistant to conventional treatment, necessitating the development of effective and safe new therapies. The percutaneous microneedle (MN) system has garnered increasing interest as a viable treatment option due to its high efficacy, minimal invasiveness, painlessness, and secure benefits. In this investigation, a sensitive MN system with multiple functions was created to combat melanoma effectively. This MN system utilized polyvinylpyrrolidone (PVP) as microneedle substrates and biocompatibility panax notoginseng polysaccharide (PNPS) as microneedle tips, which encapsulated PVP-stabilized CuO2 nanoparticles as a therapeutic agent and disulfiram-containing F127 micelles to enhance the tumor treatment effect. The MN system had sufficient mechanical properties to pierce the skin, and the excellent water solubility of PNPS brought high-speed dissolution properties under the bio conditions, allowing the MNs to effectively penetrate the skin and deliver the CuO2 nanoparticles as well as the drug-loaded micelles to the melanoma site. CuO2 nanoparticles released by the MN system generated Cu2+ and H2O2 in the tumor acidic environment to achieve self-supply of hydrogen peroxide to chemodynamic therapy (CDT). In addition, Cu2+ was chelated with disulfiram to produce CuET, which killed tumor cells. And the MN system had excellent near-infrared (NIR) photothermal properties due to the loading of CuO2 nanoparticles and induced localized thermotherapy in the melanoma region to further inhibit tumor growth. Thus, the designed MN system accomplished effective tumor suppression and minimal side effects in vivo via combined therapy, offering patients a safe and effective option for melanoma treatment.

An ultrasmall PVP-Fe-Cu-Ni-S nano-agent for synergistic cancer therapy through triggering ferroptosis and autophagy.

Photothermal therapy (PTT) is an emerging field where photothermal agents could convert visible or near-infrared (NIR) radiation into heat to kill tumor cells. However, the low photothermal conversion efficiency of photothermal agents and their limited antitumor activities hinder the development of these agents into monotherapies for cancer. Herein, we have fabricated an ultrasmall polyvinylpyrrolidone (PVP)-Fe-Cu-Ni-S (PVP-NP) nano-agent via a simple hot injection method with excellent photothermal conversion efficiency (∼96%). Photothermal therapy with this nano-agent effectively inhibits tumor growth without apparent toxic side-effects. Mechanistically, our results demonstrated that, after NIR irradiation, PVP-NPs can induce ROS/singlet oxygen generation, decrease the mitochondrial membrane potential, release extracellular Fe2+, and consume glutathione, triggering autophagy and ferroptosis of cancer cells. Moreover, PVP-NPs exhibit excellent contrast enhancement according to magnetic resonance imaging (MRI) analysis. In summary, PVP-NPs have a high photothermal conversion efficiency and can be applied for MRI-guided synergistic photothermal/photodynamic/chemodynamic cancer therapy, resolving the bottleneck of existing phototherapeutic agents.

Improving Solubility and Permeability of Hesperidin through Electrospun Orange-Peel-Extract-Loaded Nanofibers.

Orange peel, which is a rich source of polyphenolic compounds, including hesperidin, is produced as waste in production. Therefore, optimization of the extraction of hesperidin was performed to obtain its highest content. The influence of process parameters such as the kind of extraction mixture, its temperature and the number of repetitions of the cycles on hesperidin content, the total content of phenolic compounds and antioxidant (DPPH scavenging assay) as well as anti-inflammation activities (inhibition of hyaluronidase activity) was checked. Methanol and temperature were key parameters determining the efficiency of extraction in terms of the possibility of extracting compounds with the highest biological activity. The optimal parameters of the orange peel extraction process were 70% of methanol in the extraction mixture, a temperature of 70 °C and 4 cycles per 20 min. The second part of the work focuses on developing electrospinning technology to synthesize nanofibers of polyvinylpyrrolidone (PVP) and hydroxypropyl-ß-cyclodextrin (HPßCD) loaded with hesperidin-rich orange peel extract. This is a response to the circumvention of restrictions in the use of hesperidin due to its poor bioavailability resulting from low solubility and permeability. Dissolution studies showed improved hesperidin solubility (over eight-fold), while the PAMPA-GIT assay confirmed significantly better transmucosal penetration (over nine-fold). A DPPH scavenging assay of antioxidant activity as well as inhibition of hyaluronidase to express anti-inflammation activity was established for hesperidin in prepared electrospun nanofibers, especially those based on HPßCD and PVP. Thus, hesperidin-rich orange peel nanofibers may have potential buccal applications to induce improved systemic effects with pro-health biological activity.

An Innovative Approach for Formulation of Rutin Tablets Targeted for Colon Cancer Treatment.

The aim of this study was the improvement of rutin solubility along with targeting its release to colon for effective treatment of colon cancer. Five formulations of compression-coated tablets were prepared with the same core composition including rutin-polyvinyl pyrrolidone K30 solid dispersion (rutin-PVP K30 SD) but differ in being coated with either frankincense alone or different combinations of frankincense with gelatin. The superior formula was selected based on the in vitro drug release then further evaluated in terms of physical properties and in vivo performance in dogs using X-ray. Moreover, in vitro cytotoxicity of rutin, rutin-PVP K30 SD, frankincense, and a mixture of rutin-PVP K30 SD with frankincense in a ratio representing their concentrations in the selected formula was assessed against human colon cancer (HCT-116) cell lines using sulforhodamine B assay. The formula (F4) with the coat consisted of 65%w/w frankincense and 35%w/w gelatin achieved acceptable in vitro controlled drug release. In vivo X-ray in dogs confirmed that F4 tablet could remain intact in the stomach and small intestine until reaching the colon. In vitro cytotoxicity revealed that mixture of rutin-PVP K30 SD with frankincense was more effective in arresting cancer cell growth than rutin or frankincense alone. Moreover, stability studies revealed that F4 tablets were physically and chemically stable. Thus, improving rutin solubility using solid dispersion technique and formulating it into frankincense-based compression-coated (F4) tablets would be a successful approach for colonic delivery of rutin with potential of improving therapeutic efficacy.

Nanoemulsion carriers of porous γ-alumina modified by polyvinylpyrrolidone and carboxymethyl cellulose for pH-sensitive delivery of 5-fluorouracil.

5-Fluorouracil (5-FU) is a cytotoxic drug with a low half-life. These features can cause some problems such as burst drug release and numerous side effects. In the present study, a pH-sensitive nanocomposite of polyvinylpyrrolidone (PVP)/carboxymethyl cellulose (CMC)/γ-alumina developed by using water in oil in water (W/O/W) double emulsion method. The fabricated emulsion has been employed as the 5-FU carrier to investigate its effects on drug half-life, side effects, drug loading efficiency (DLE), and drug entrapment efficiency (DEE). Analyzing the FTIR and XRD indicated the successful loading of 5-FU into the nanocarrier and affirmed the synthesized nanocomposite's chemical bonding and crystalline features. Furthermore, by using DLS and Zeta potential assessment, size and undersize distribution, as well as the stability of the drug-loaded nanocomposite were determined, which demonstrated the monodisperse and stable nanoparticles. Moreover, the nanocomposites with spherical shapes and homogeneous surfaces were shown in FE-SEM, which indicated good compatibility for the constituents of the nanocomposites. Moreover, by employing BET analysis the porosity has been investigated. Drug release pattern was studied, which indicated a controlled drug release behavior with above 96 h drug retention. Besides, the loading and entrapment efficiencies were obtained 44 % and 86 %, respectively. Furthermore, the curve fitting technique has been employed and the predominant release mechanism has been determined to evaluate the best-fitted kinetic models. MTT assay and flow cytometry assessment has been carried out to investigate the cytotoxic effects of the fabricated drug-loaded nanocomposite on MCF-7 and normal cells. The results showed enhanced cytotoxicity and late apoptosis for the PVP/CMC/γ-alumina/5-FU. Based on the MTT assay outcomes on normal cell lines (L929), which indicated above 90 % cell viability, the biocompatibility and biosafety of the synthesized nanocarrier have been confirmed. Moreover, due to the porosity of the PVP/CMC/γ-alumina, this nanocarrier can exploit from high specific surface area and be more sensitive to environmental conditions such as pH. These outcomes propose that the novel pH-sensitive PVP/CMC/γ-alumina nanocomposite can be a potential candidate for drug delivery applications, especially for cancer therapy.

Assessing transfer of aluminum during tea brewing and associated population health risks.

Tea is consumed widely around the world owing to its refreshing taste and potential health benefits. However, drinking tea is considered a major route for dietary aluminum exposure in areas where tea consumption is relatively large. To assess the health risk associated with drinking tea, the contamination level of aluminum was determined in 81 tea samples. The transfer rate of aluminum during tea brewing was investigated. Then based on the site-specific exposure parameters such as consumption data and body weight for six different subpopulations in Fujian, the exposure risks were estimated using a probabilistic approach. Results demonstrate that the contents of aluminum in green tea, white tea, oolong tea, and black tea were significantly different according to the one-way ANOVA analysis (p < 0.05). The transfer rate of aluminum were 32.6%, 31.6%, 26.3%, and 14% for white tea, black tea, oolong tea, and green tea, respectively. With respect to the oral reference dose, the exposure of inhabitants in Fujian to aluminum through drinking tea is under control (even at the 99th percentile).

Ultrasmall zirconium carbide nanodots for synergistic photothermal-radiotherapy of glioma.

Glioma is characterized by highly invasive, progressive, and lethal features. In addition, conventional treatments have been poorly effective in treating glioma. To overcome this challenge, synergistic therapies combining radiotherapy (RT) with photothermal therapy (PTT) have been proposed and extensively explored as a highly feasible cancer treatment strategy. Herein, ultrasmall zirconium carbide (ZrC) nanodots were successfully synthesized with high near-infrared absorption and strong photon attenuation for synergistic PTT-RT of glioma. ZrC-PVP nanodots with an average size of approximately 4.36 nm were prepared by the liquid exfoliation method and modified with the surfactant polyvinylpyrrolidone (PVP), with a satisfactory absorption and photothermal conversion efficiency (53.4%) in the near-infrared region. Furthermore, ZrC-PVP nanodots can also act as radiosensitizers to kill residual tumor cells after mild PTT due to their excellent photon attenuating ability, thus achieving a significant synergistic therapeutic effect by combining RT and PTT. Most importantly, both in vitro and in vivo experimental results further validate the high biosafety of ZrC-PVP NDs at the injected dose. This work systematically evaluates the feasibility of ZrC-PVP NDs for glioma treatment and provides evidence of the application of zirconium-based nanomaterials in photothermal radiotherapy.

Is It Possible to Improve the Bioavailability of Resveratrol and Polydatin Derived from Polygoni cuspidati Radix as a Result of Preparing Electrospun Nanofibers Based on Polyvinylpyrrolidone/Cyclodextrin?

The low bioavailability of resveratrol and polydatin obtained from Polygoni cuspidati extract limits the application of their pro-health properties. While nanofibers have attracted increasing attention in nutrition delivery due to their special properties, including an increase in the dissolution and permeability, which affects the bioavailability. Therefore, it is justified to obtain nanofibers from Polygoni cuspidati extract, which showed antioxidant and anti-inflammatory properties as a result of a presence of stilbene analogs in the Polygoni cuspidati extract (especially resveratrol and polydatin). In the first stage of the work, using the Design of Experiment (DoE) approach, the Polygoni cuspidati extract (70% of methanol, temperature 70 °C and 4 cycles) was obtained, which showed the best antioxidant and anti-inflammatory properties. Using the Polygoni cuspidati extract as a substrate, nanofibers were obtained by electrospinning. The identification of nanofibers was confirmed on the basis of the analysis of changes in XRPD diffractograms, SEM picture and FTIR-ATR spectra. Obtaining nanofibers from the Polygoni cuspidati extract significantly improved the solubility of resveratrol and polydatin (approx. 6-fold comparing to pure substance). As a consequence, the penetration coefficients of both tested resveratrol and polydatin also increased. The proposed strategy for the preparation of nanofibers from the Polygoni cuspidati extract is an innovative approach to better use the synergy of biological action of active compounds present in extracts. It is especially during the development of nutraceuticals based on the use of selected stilbenes.

Study on Integrated Pharmacokinetics of the Component-Based Chinese Medicine of Ginkgo biloba Leaves Based on Nanocrystalline Solid Dispersion Technology.

Background: To improve the dissolution and bioavailability of the component-based Chinese medicine of Ginkgo biloba leaves (GBCCM), a novel nanocrystalline solid dispersion of GBCCM (GBCCM NC-SD) was first prepared. Methods: GBCCM mainly containing high pure flavonoid aglycones (FAs) and terpenoid lactones (TLs) was used as the model drug. PVP K30 and SDS were used as solubilizers, combined stabilizers and carriers, and GBCCM NC-SD was prepared by high-pressure homogenization combined with freeze-dryer. Morphology and crystal characteristic of GBCCM NC-SD were analyzed. The dissolution and bioavailability evaluation were performed to investigate the feasibility of GBCCM NC-SD by in vitro dissolution and in vivo integrated pharmacokinetic models. Results: After homogenizing for 30 cycles under the pressure of 650 bar and freeze-drying, GBCCM NC-SD with uniform quality would be obtained. The particle size, PDI and zeta potential were found to be 335.9 ± 32.8 nm, 0.29 ± 0.02 and -28.4 ± 0.7 mV respectively. Based on charged aerosol detector (CAD) technology, a new chromatographic method for simultaneous detection of eight components in GBCCM was developed. In vitro drug release study showed that the cumulative dissolution of FAs and TLs in GBCCM NC-SD increased from 12.77% to 52.92% (P < 0.01) and 90.91% to 99.21% (P < 0.05) respectively. In comparison with physical mixture of GBCCM and stabilizer (PM), the integrated pharmacokinetics AUC0-t of FAs and TLs in GBCCM NC-SD were significantly increased (P < 0.05), and the T1/2 of TLs was also significantly prolonged (P < 0.05). Conclusion: This study demonstrated that novel GBCCM NC-SD was prepared using Polyvinylpyrrolidone K30 (PVP K30) and Sodium dodecyl sulfate (SDS) as a synergetic stabilizer and also provided a feasible way to improve the dissolution and oral bioavailability of poorly soluble candidate antihypertensive drugs.

Sorafenib-Loaded Copper Peroxide Nanoparticles with Redox Balance Disrupting Capacity for Enhanced Chemodynamic Therapy against Tumor Cells.

Chemodynamic therapy (CDT) is a promising hydroxyl radical (•OH)-mediated tumor therapeutic method with desirable tumor specificity and minimal side effects. However, the efficiency of CDT is restricted by the pH condition, insufficient H2O2 level, and overexpressed reductive glutathione (GSH), making it challenging to solve these problems simultaneously to improve the efficacy of CDT. Herein, a kind of polyvinylpyrrolidone-stabilized, sorafenib-loaded copper peroxide (CuO2-PVP-SRF) nanoparticle (NPs) was designed and developed for enhanced CDT against tumor cells through the synergetic pH-independent Fenton-like, H2O2 self-supplying, and GSH depletion strategy. The prepared CuO2-PVP-SRF NPs can be uptaken by 4T1 cells to specifically release Cu2+, H2O2, and SRF under acidic conditions. The intracellular GSH can be depleted by SRF-induced system xc- dysfunction and Cu2+-participated redox reaction, causing the inactivation of GPX4 and generating Cu+. A great amount of •OH was produced in this reducing capacity-disrupted condition by the Cu+-mediated Fenton-like reaction, causing cell apoptosis and lipid hydroperoxide accumulation-induced ferroptosis. They display an excellent 4T1 cell killing outcome through the improved •OH production capacity. The CuO2-PVP-SRF NPs display elevated therapeutic efficiency of CDT and show good promise in further tumor treatment applications.