Intravitreal injection of rapamycin-loaded polymeric micelles for inhibition of ocular inflammation in rat model

Wu, Wei; He, Zhifen; Zhang, Zhaoliang; Yu, Xinxin; Song, Zongming; Li, Xingyi

doi:10.1016/j.ijpharm.2016.09.013

Cited by 47 publications

(26 citation statements)

References 38 publications

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“…27 Moreover, insoluble drugs (eg, curcumin, rapamycin) can be encapsulated in mPEG-PCL. 28,29 In the present study, chrysin-NPs produced using mPEG-PCL were found to be nanosized (66.86 nm) Notes: A549 cells were treated with chrysin-NPs or free chrysin for 48 h. Cell viabilities were assessed using a MTT assay. Data shows mean ± sD (n=8).…”

Section: Discussionmentioning

confidence: 64%

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Kim¹,

Lim

Shim³

et al. 2017

IJN

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Chrysin is a flavone that is found in several plants and in honeycomb and possesses various biological activities. However, its low solubility means it has poor bioavailability, which must be resolved to enable its pharmaceutical applications. In the present study, chrysin was incorporated into methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles (chrysin-NPs) using the oil-in-water technique in order to overcome problems associated with chrysin. The properties of chrysin-NPs were analyzed, and their anticancer effects were investigated in vitro and in vivo. Chrysin-NPs were 77 nm sized (as determined by dynamic laser light scattering) and showed a monodisperse distribution. The zeta potential of chrysin-NPs was −2.22 mV, and they were spherically shaped by cryo-transmission electron microscopy (cryo-TEM). The loading efficiency of chrysin-NPs was 46.96%. Chrysin-NPs retained the cytotoxicity of chrysin in A549 cells. The therapeutic efficacies of chrysin-NPs were compared with those of chrysin in an A549-derived xenograft mouse model. Chrysin-NPs were intravenously injected at a 10 times lower dosage than chrysin 3 times per week (q2d×3/week). However, free chrysin was orally administrated 5 times per week (q1d×5/week). Chrysin-NP-treated group showed significant tumor growth delay, which was similar to that of chrysin-treated group, despite the considerably lower total dosage. These results suggest that the injectable chrysin-NPs enhance therapeutic efficacy in vivo and offer a beneficial formulation for chemotherapy.

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Section: Discussionmentioning

confidence: 64%

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Kim¹,

Lim

Shim³

et al. 2017

IJN

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“…It is believed that RPM can inhibit T and B cell activation and proliferation [26]. However, it has also been reported that T cell proliferation is not affected when treated with RPM at an appropriate concentration [27]. Meanwhile, it has also been reported that RPM can protect neuronal cells from apoptosis by inducing autophagy, which indicates that RPM has a cytoprotective effect [28, 29].…”

Section: Discussionmentioning

confidence: 99%

Differential Role of Rapamycin in Epidermis-Induced IL-15-IGF-1 Secretion via Activation of Akt/mTORC2

Bai¹,

Xu²,

Zhang³

et al. 2017

Cell Physiol Biochem

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Backgroud/Aims: The effects of rapamycin (RPM) on wound healing have been previously studied. However, reciprocal contradictory data have been reported, and the underlying mechanism remains unclear. This study aims to uncover differential role of RPM in regulation of wound healing and explore the possible mechanism. Methods: C57BL/6J mice and epidermal cells were treated with different doses of RPM. The wound re-epithelialization was observed by hematoxylin and eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by immunohistochemistry and quantitative real-time PCR. Epidermal cell survival was determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2 pathway were examined by western blot analysis. Results: This study showed that differential doses of RPM could lead to separate consequences in epidermis. Histological analyses showed that low-dose RPM promoted wound healing, and enhanced the expression of IL-15 and IGF-1. Furthermore, western blot analysis showed that the effect of low-dose RPM in epidermis were not through mTORC1 pathway. Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway. Conclusion: This study for the first time demonstrated that RPM-mediated wound healing was dose-dependent.

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“…Rap was separated by using a C18 Column (Kromasil ® , 5 μm, 4.6×250 mm; Akzo Nobel, Bohus, Sweden) with acetonitrile and water (75:25, v/v) as a mobile phase delivered at a flow rate of 1 mL/min. The column temperature was set to 40 °C 31. Rap was detected at 277 nm, with an injection volume of 50 μL.…”

Section: Methodsmentioning

confidence: 99%

<p>Intravesical delivery of rapamycin via folate-modified liposomes dispersed in thermo-reversible hydrogel</p>

Yoon¹,

Chang²,

Goo³

et al. 2019

IJN

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Purpose To develop an intravesical instillation system for the treatment of bladder cancer, rapamycin (Rap) was encapsulated into liposomes and then homogeneously dispersed throughout a poloxamer 407 (P407)-based hydrogel. Methods Rap-loaded conventional liposomes (R-CL) and folate-modified liposomes (R-FL) were prepared using a film hydration method and pre-loading technique, and characterized by particle size, drug entrapment efficiency, and drug loading. The cellular uptake behavior in folate receptor-expressing bladder cancer cells was observed by flow cytometry and confocal laser scanning microscopy using a fluorescent probe. In vitro cytotoxic effects were evaluated using MTT assay, colony forming assay, and Western blot. For in vivo intravesical instillation, Rap-loaded liposomes were dispersed in P407-gel, generating R-CL/P407 and R-FL/P407. Gel-forming capacities and drug release were evaluated. Using the MBT2/Luc orthotopic bladder cancer mouse model, in vivo antitumor efficacy was evaluated according to regions of interest (ROI) measurement. Results R-CL and R-FL were successfully prepared, at approximately <160 nm, 42% entrapment efficiency, and 57 μg/mg drug loading. FL cellular uptake was enhanced over 2-fold than that of CL; folate receptor-mediated endocytosis was confirmed using a competitive assay with folic acid pretreatment. In vitro cytotoxic effects increased dose-dependently. Rap-loaded liposomes inhibited mTOR signaling and induced autophagy in urothelial carcinoma cells. With gelation time of <30 seconds and gel duration of >12 hrs, both R-CL/P407 and R-FL/P407 preparations transformed into gel immediately after instillation into the mouse bladder. Drug release from the liposomal gel was erosion controlled. In orthotopic bladder cancer mouse model, statistically significant differences in ROI values were found between R-CL/P407 and R-FL/P407 groups at day 11 ( P =0.0273) and day 14 ( P =0.0088), indicating the highest tumor growth inhibition by R-FL/P407. Conclusion Intravesical instillation of R-FL/P407 might represent a good candidate for bladder cancer treatment, owing to its enhanced retention and FR-targeting.

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Intravitreal injection of rapamycin-loaded polymeric micelles for inhibition of ocular inflammation in rat model

Cited by 47 publications

References 38 publications

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Differential Role of Rapamycin in Epidermis-Induced IL-15-IGF-1 Secretion via Activation of Akt/mTORC2

<p>Intravesical delivery of rapamycin via folate-modified liposomes dispersed in thermo-reversible hydrogel</p>

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