a-periprosthetic-joint-candida-albicans-infection-model-in-mouse

A Periprosthetic Joint <em>Candida albicans</em> Infection Model in Mouse

Periprosthetic joint infection (PJI) is one of the common infections caused by Candida albicans (C. albicans), which increasingly concerns surgeons and ...

a-catheter-related-candida-albicans-infection-model-in-mouse

A Catheter-Related <em>Candida albicans</em> Infection Model in Mouse

Catheter-related infection (CRI) is a common nosocomial infection caused by candida albicans during catheter implantation. Typically, biofilms are formed ...

Xi’an Jiaotong University

Drug solubility and permeability are two major challenges affecting oral delivery, the most popular route of drug administration. Polymeric micelles is an emerging technology for overcoming the current oral drug delivery hurdles. Previous study primarily focused on developing new polymers or new micellar systems and a systematic investigation of the impact of the polymer block length on solubility and permeability enhancement; and their subsequent effect on oral bioavailability is lacking. Herein, by using paclitaxel, a poorly soluble P-glycoproteins (P-gp) substrate, as a model, we aim to assess and compare the drug-loaded micelles prepared with two different molecular weight of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL), with the ultimate goal of establishing a strong scientific rationale for proper design of formulations for oral drug delivery. PEG-b-PCL (750:570) (PEG-b-PCL) and PEG-b-PCL (5k:10k) (PEG-b-PCL) effectively enhanced the solubility of paclitaxel compared to the free drug. PEG-b-PCL (750:570) increased both P-gp and non P-gp substrate cellular uptake and increased the apparent permeability coefficient of a P-gp substrate. In vivo animal study showed that PEG-b-PCL micelles efficiently enhanced the oral bioavailability of paclitaxel. In addition to solubility enhancement, polymer choice also plays a pivotal role in determining the oral bioavailability improvement, probably via permeation enhancement. In conclusion, the knowledge gained in this study enables rational design of polymeric micelles to overcome the current challenges of oral drug delivery and it also provides a basis for future clinical translation of the technology.

Oral delivery of paclitaxel by polymeric micelles: A comparison of different block length on uptake, permeability and oral bioavailability.

To investigate the effect of low-magnitude high frequency vibration (LMHFV) on proliferation, migration ability and osteogenic differentiation of human periodontal ligament stem cells(hPDLSCs).

[Effect of low-magnitude high frequency vibration on osteogenic differentiation of human periodontal ligament stem cells].

Candida albicans-related infections are common infections in clinic, among which biofilm-associated infections are most devastating and challenging to overcome. Myricetin (MY) is a plant-derived natural product with various pharmacological activities. Its anti-biofilm effect against C. albicans and its ability to increase the antifungal effect of miconazole nitrate (MN) were unclear and yet need to be explored.

In vitro and in vivo effects of the combination of myricetin and miconazole nitrate incorporated to thermosensitive hydrogels, on C. albicans biofilms.

Retinal diseases, such as age-related macular degeneration and diabetic retinopathy, are the leading causes of blindness worldwide. The mainstay of treatment for these blinding diseases remains to be surgery, and the available pharmaceutical therapies on the market are limited, partially owing to various biological barriers in hindering the delivery of therapeutics to the retina. The nanoparticulate drug delivery system confers the capability for delivering therapeutics to the specific ocular targets and, hence, potentially revolutionizes the current treatment landscape of retinal diseases. While the research to date indicates the enormous therapeutics potentials of the nanoparticulate delivery systems, the successful translation of these systems from the bench to bedside is challenging and requires a combined understanding of retinal pathology, physiology of the eye, and particle and formulation designs of nanoparticles. To this end, the review begins with an overview of the most prevalent retinal diseases and related pharmacotherapy. Highlights of the current challenges encountered in ocular drug delivery for each administration route are provided, followed by critical appraisal of various nanoparticulate drug delivery systems for the retinal diseases, including their formulation designs, therapeutic merits, limitations, and future direction. It is believed that a greater understanding of the nano-biointeraction in eyes will lead to the development of more sophisticated drug delivery systems for retinal diseases.

Nanoparticulate Drug Delivery to the Retina.

Ocular safety/biocompatibility is an essential element of ophthalmic drug delivery. We previously applied poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-b-PCL) micelles to deliver dasatinib for the management of proliferative vitreoretinopathy (PVR) in vitro. Herein, we seek to ascertain the ocular safety/compatibility of blank and dasatinib loaded PEG-b-PCL micelles, which will set the stage for the future in vivo efficacy evaluations and/or clinical translation for PVR or other eye diseases.

Safety assessment of polymeric micelles as an ophthalmic drug delivery system for intravitreal administration of dasatinib.

Corneal neovascularization (CNV) is one of the most important causes of visual impairment worldwide. Dasatinib, a poorly water-soluble tyrosine kinase inhibitor with dual Src family kinase and platelet derived growth factor receptor inhibiting capability, has great potential in the treatment of CNV. In this study, dasatinib was successfully encapsulated into a nanostructured lipid carrier (Dasa-NLC) and the size was approximately 78 nm with a small polydispersity index. The NLC increased the solubility of dasatinib by more than 1220 times, sustained the drug release, reduced the ocular toxicity and facilitated its penetration into the cornea. Dasa-NLC significantly inhibited the proliferation, migration and tube formation of HUVEC cells, the three most important angiogenesis-related cellular changes of the CNV. Next, the in vivo anti-CNV effect of Dasa-NLC was evaluated using an alkaline burned mice CNV model, in which the development of the CNV and pathological changes of the cornea were significantly inhibited. The immunohistochemistry analysis indicated that Dasa-NLC could inhibit both the expression and activation of Src family kinase, a key component in the angiogenesis cascade. Therefore, Dasa-NLC showed considerable promise in the treatment of CNV.

Dasatinib loaded nanostructured lipid carriers for effective treatment of corneal neovascularization.

  catheter-related infection (CRI) is a great challenge in clinic now, mainly due to the difficulty in eradicating the biofilms.  In this study, the mechanism of the antibiofilm effect of myricetin (MY) on  was illustrated. A film forming system (FFS) containing MY and miconazole nitrate (MN) was developed, optimized, and evaluated. The anti-infection effect of MY+MN@FFS against  CRI was investigated .  To clarify the mechanism of the action of MY, the influence of MY on each key process of the formation of  biofilms was evaluated. To deliver MY and MN into the skin and form a drug reservoir on the surface of the skin, the FFS was used as a carrier and MY+MN@FFS was developed, optimized, and evaluated. After preliminary confirmation of drug safety, a percutaneously inserted  CRI mouse model was established to investigate the  anti-infection effect of MY+MN@FFS by fluorescence microscopy and scanning electron microscopy on the outer surface of the catheters, hematoxylin/eosin staining, and periodic acid-Schiff staining of the mice skin tissues.  MY was found to inhibit the morphological transition of  and the secretion of exopolysaccharides, resulting in a reduction in biofilms. MY+MN@FFS exhibited excellent properties and no irritation to mice skin. In an  anti-infection study, MY+MN@FFS exhibited an excellent preventive effect against percutaneously inserted  CRI.  MY+MN@FFS might be a potential approach for effectively preventing percutaneously inserted  CRI in clinic.

Development and Evaluation of a Film Forming System Containing Myricetin and Miconazole Nitrate for Preventing  Catheter-Related Infection.

Vulvar candidiasis (VVC) is a vaginitis caused by vaginal mucosa infection of Candida, which greatly impairs women's health. Although there are more and more thiazoles on the market, new classes of antifungal drugs are still missing, it is still challenging to treat azole-resistant candidal vaginitis. We found that L-Se-methylselenocysteine (L-SeMC) could effectively inhibit the growth of Candida albicans, reduce the density and length of the mycelia. To extend the retention time of L-SeMC in the vaginal tract and enhance its therapeutic effect for VVC, a mucoadhesive thermogel (NAC-HA thermogel) was successfully synthesized and prepared. The gelation window was around 29-56 °C for L-SeMC loaded mucoadhesive thermogel (L-SeMC@NAC-HA thermogel), which exhibited a sustained release profile in the in vitro release study and an extended retention time in the vaginal tract. Besides, L-SeMC@NAC-HA thermogel exhibited a good safety profile in the in vivo safety study. The in vivo anti-VVC effect was examined in a rat VVC model and L-SeMC@NAC-HA thermogel significantly reduced the number of Candida albicans in the vaginal secreta, mitigated the vaginal damage and reduced the secretion of proinflammatory factors (TNF-α, IL-1α and IL-β). Therefore, it is a promising therapy for the clinical treatment of VVC in the near future.

L-Se-methylselenocysteine loaded mucoadhesive thermogel for effective treatment of Vulvar candidiasis.

Non-functional scars commonly form after cutaneous injuries. At present, most clinical treatments for scar eradication typically have long treatment courses, low curative effects, and are expensive. In this research, three hydrogels, namely chitin hydrogel, β-glucan hydrogel, and hybrid hydrogel composed of chitin and β-glucan, were successfully prepared, and they exhibited good shear thinning property and bioadhesiveness. In a full-thickness skin defect mouse model, the three hydrogels were found to effectively promote wound closure and inhibit scar formation. Through the immunohistochemistry staining and immunofluorescence staining of the wound tissues, the hydrogels could significantly promote the formation of collagen III, the regeneration of hair follicles, and the expression of keratin K14 and K15. They could also regulate the production of VEGF and immune factors such as IL-10 and IL-12, and inhibit the expression of the fibroblast regulatory factor En-1 in the wound site, which correlated well with their improved wound healing promoting effect and anti-scarring effect. Among all the hydrogels, the hybrid hydrogel was the best to promote wound healing and inhibit scarring. This study, for the first time, proved the excellent therapeutic effect of chitin and β-glucan hydrogels in the management of wound healing and skin regeneration without scar formation, which will lay a solid foundation for the development of skin regeneration medication and future clinical transformation.

A hybrid hydrogel composed of chitin and β-glucan for the effective management of wound healing and scarring.

Shikonin is well known for its anti-inflammatory activity in cardiovascular diseases. However, the application of shikonin is limited by its low water solubility and poor bioavailability. Methoxy poly (ethylene glycol)-b-poly (ε-caprolactone) (MPEG-PCL) is considered a promising delivery system for hydrophobic drugs. Therefore, in this study, we prepared shikonin-loaded MPEG-PCL micelles and investigated their effect on endothelial-to-mesenchymal transition (EndMT) induced by inflammatory cytokines.

Combined Shikonin-Loaded MPEG-PCL Micelles Inhibits Effective Transition of Endothelial-to-Mesenchymal Cells.

Hepatic ischemia-reperfusion injury (HIRI) is the main reason for liver dysfunction or failure after liver resection and liver transplantation. As excess accumulation of reactive oxygen species (ROS) is the leading factor, ceria nanoparticle, a cyclic reversible antioxidant, is an excellent candidate for HIRI.

Mesoporous Hollow Manganese Doped Ceria Nanoparticle for Effectively Prevention of Hepatic Ischemia Reperfusion Injury.

The effect of traditional treatment for melanoma is quite limited, especially for its recurrence. As the major components of yeast cell wall, chitin and β-glucan exhibit good immune activation effect and are promising candidates for adjuvant. Therefore, melanoma cell membrane (CM) and indocyanine green (ICG) was loaded in a chitin and β-glucan hybrid hydrogel to achieve an enhanced anti-melanoma therapy.

Qingqing Li

School of Pharmacy,
Health Science Center,
School of Pharmacy, Health Science Center

Xi’an Jiaotong University

A Periprosthetic Joint Candida albicans Infection Model in Mouse

A Catheter-Related Candida albicans Infection Model in Mouse

Qingqing Li

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}School of Pharmacy,Health Science Center,School of Pharmacy, Health Science Center

Xi’an Jiaotong University

A Periprosthetic Joint Candida albicans Infection Model in Mouse

A Catheter-Related Candida albicans Infection Model in Mouse

School of Pharmacy,
Health Science Center,
School of Pharmacy, Health Science Center