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Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.
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Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO3-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO3-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO3 ‒ in the active backing layer to produce carbon dioxide gas (CO2). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO3-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO3-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.
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Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells (MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles (NP) with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel (DTX) in NP, delivered MSC accumulated in the lung. Both MSC/A549 cell experiments and MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.
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Objective To study the effects of total saponins of Chaenomeles speciosa on release of β-hexosaminidase from rat basophilic leukemia-2H3 ( RBL-2H3 ) mast cells. Methods After rat RBL-2H3 mast cells were prepared, total saponins of Chaenomeles speciosa and the RBL-2H3 mast cells were co-cultured.The toxic effects of total saponins of Chaenomeles speciosa on mast cells were detected by MTT method, β-hexosaminidase release rate was measured by fluorescence quantitative spectrophotometric method, and cell supernatants of tumor necrosis factor-α( TNF-α) release were detected by ELISA. Results After total saponins of Chaenomeles speciosa were co-cultured with RBL-2H3 mast cells with different antigen stimulation, β-hexosaminidase release rates and the levels of TNF-α of mast cells significantly decreased compared with the control group. Conclusion Total saponins of Chaenomeles speciosa inhibit the degranulation of RBL-2H3 mast cells in a dose dependent manner, which provids basis for studying mechanism of inhibiting allergic reactions.
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Objective To investigate the effects of magnetic iron-oxide (Fe3O4) nanoparticles with different skin materials on cytotoxicity against human cervix cancer HeLa cells.Methods The Fe3O4 nanoparticles were prepared by solvent-free dissolving method and then covered with poly(lactic-co-glycolic acid) (PLGA) and cholic acid (CA)-PLGA respectively.After the characterization,the uptake of nanoparticles by HeLa cells was observed by laser scanning confocal microscopy,and thiazolyl blue tetrazolium bromide (MTF) assay was used to assess the cytotoxcity of the Fe3O4-loaded nanoparticles against HeLa cells.Results The size of single Fe3O4 nanoparticle was about 7 nm.The Fe3O4-loaded PLGA and CA-PLGA nanoparticles were spherical in shape under transmission electron microscope,around 200 nm in diameter,and the theoretical drug-loading capacity was 10％.At the same Fe3O4 nanoparticles concentration of 25 μg/ml,the Fe3O4-loaded CA-PLGA nanoparticles showed less toxicity than Fe3O4-loaded PLGA nanoparticles.Conclusions Star-shaped copolymer CA-PLGA is promising in decreasing cytotoxicity of magnetic Fe3O4 nanoparticles and expanding its application in living organisms.
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Star-shaped block polymers have recently attracted considerable attention owing to their unique properties and applicability in nanomedicine development.Compare to linear polymer and hyper-branched polymers,star-shaped block polymers have more advantages due to the unique structure.Star-shaped block polymer has become a desirable molecular biomaterial for delivery therapeutics and diagnostic agent to the diseased cells.This paper reviews the research about star-shaped block polymers and nanomedicine development in using them as drug and gene delivery carriers.
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Objective Mannitol-poly(D,L-lactide-co-glycolide) (M-PLGA),a star-shaped biodegradable polymer,was synthesized with the intent in this research,to provide novel nanoformulation for cervical cancer chemotherapy.Methods The novel star-shaped copolymer was prepared by ring-opening polymerization,and characterized by NMR.The docetaxel-loaded M-PLGA nanoparticles,prepared by modified nano-precipitation method,were observed to be near-spherical shape with narrow size distribution.Results The CLSM results showed the uptake level of M-PLGA NPs was higher than PLGA NPs in Hela cells.A significantly higher level of cytotoxicity was achieved by docetaxel-loaded M-PLGA NPs than that of commercial Taxotere and docetaxel-loaded PLGA NPs,indicating that the star-shaped biodegradable polymer M-PLGA could be superior to the linear polymer PLGA as a drug carrier.The study on drug loading and encapsulation efficiency also proved that star-shaped M-PLGA could carry higher level of drug than linear polymer,therefore could be more efficient for cancer treatment.Conclusions In conclusion,the star-shaped M-PLGA copolymer may be used as a potential and promising drug-loaded biomaterial applied in developing novel nanoformulations for cervical cancer therapy.