Preparation and in vitro evaluation of vaginal formulations including siRNA and paclitaxel-loaded SLNs for cervical cancer

Büyükköroğlu, Gülay; Şenel, Behiye; Başaran, Ebru; Yenilmez, Evrim; Yazan, Yasemin

doi:10.1016/j.ejpb.2016.10.017

Cited by 50 publications

(13 citation statements)

References 51 publications

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“…PDI values ≤0.1 indicate the highest quality of dispersion. Most researchers recognize PDI values ≤0.3 as optimum values; however, values ≤0.5 are also acceptable [32]. According to literature, quality and monodisperse PLGA NPs and CS-coated PLGA NPs have been prepared.…”

Section: Resultsmentioning

confidence: 99%

Clarithromycin-Loaded Poly (Lactic-co-glycolic Acid) (PLGA) Nanoparticles for Oral Administration: Effect of Polymer Molecular Weight and Surface Modification with Chitosan on Formulation, Nanoparticle Characterization and Antibacterial Effects

2019

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Clarithromycin (CLR) is a member of the macrolide antibiotic group. CLR has low systemic oral bioavailability and is a drug of class II of the Biopharmaceutical Classification System. In many studies, using nanoparticles (NPs) as a drug delivery system has been shown to increase the effectiveness and bioavailability of active drug substances. This study describes the development and evaluation of poly (lactic-co-glycolic acid) (PLGA) NPs and chitosan (CS)-coated PLGA NPs for oral delivery of CLR. NPs were obtained by nanoprecipitation technique and characterized in detail, and the effect of three molecular weights (Mw1: 7.000–17.000, Mw2: 38.000–54.000, Mw3: 50.000–190.000) of PLGA and CS coating on particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), and release properties etc. were elucidated. Gastrointestinal stability and cryoprotectant effect tests were performed on the NPs. The PS of the prepared NPs were in the range of 178 to 578 nm and they were affected by the Mw and CS coating. In surface-modified formulations with CS, the ZP of the NPs increased significantly to positive values. EE% varied from 62% to 85%, depending upon the Mw and CS coating. In vitro release studies of CLR-loaded NPs showed an extended release up to 144 h. Peppas–Sahlin and Weibull kinetic model was found to fit best for CLR release from NPs. By the broth microdilution test method, the antibacterial activity of the formulations was determined on Staphylococcus aureus (ATCC 25923), Listeria monocytogenes (ATCC 1911), and Klebsiella pneumoniae (ATCC 700603). The structures of the formulations were clarified by thermal (DSC), FT-IR, and 1H-NMR analysis. The results showed that PS, ZP, EE%, and dissolution rates of NPs were directly related to the Mw of PLGA and CS coating.

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Section: Resultsmentioning

confidence: 99%

Clarithromycin-Loaded Poly (Lactic-co-glycolic Acid) (PLGA) Nanoparticles for Oral Administration: Effect of Polymer Molecular Weight and Surface Modification with Chitosan on Formulation, Nanoparticle Characterization and Antibacterial Effects

2019

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“…As a means of drug delivery, nanoparticles could enhance the water solubility, stability, and bioavailability of drugs, so as to prolong their circulation in blood compartments 39. A study conducted by G B et al40 has indicated that the prepared nanoparticle containing a chemotherapeutic drug paclitaxel could locally release the paclitaxel at the target site to reduce the dose into the systemic circulation. Therefore, whether SNG-loaded nanocapsules can target to treat cervical cancer and improve its bioavailability needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

<p>Sanguinarine exhibits potent efficacy against cervical cancer cells through inhibiting the STAT3 pathway in vitro and in vivo</p>

Zhang¹,

Zhang²,

Venkat³

et al. 2019

CMAR

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Background Cervical cancer is the third most common malignancy among female cancer patients worldwide. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which regulates a variety of cancer cellular physiological activities including cervical cancer. Sanguinarine (SNG) is a natural plant-derived benzophenanthridine alkaloid that possesses antitumor activities in several cancer cells. However, its anticancer effect on human cervical cancer cells and the underlying mechanisms have not been fully defined. Methods In this study, the inhibitory effect of SNG on the proliferation and growth of HeLa cell was detected by MTT assay. Next, cell cycle and apoptosis of HeLa cells was analyzed using Annexin-V/PI double staining and flow cytometry. Then, we measured intracellular ROS generation induced by SNG in HeLa cells by DCFH-DA (10 μM) staining, and the expression level of p-STAT3 and STAT3 was detected by Western blot. Finally, in order to study the effect of SNG on tumor growth in vivo, athymic nude mice were used in the vivo experiments. Result This study showed that SNG dose-dependently decreased the tumor cell proliferation and induced a marked increase in cell apoptosis in HeLa cells. Western blot analysis results revealed that SNG-induced antitumor effect might be mediated by STAT3 inhibition. SNG increased the expression of the proapoptotic protein Bax and reduced the expression of the antiapoptotic protein Bcl-2. We further found that SNG dose-dependently increased ROS level in Hela cells. Moreover, pretreatment with N-acetyl-l-cysteine, a scavenger of ROS, almost reversed the SNG-induced anticancer effect. In addition, SNG inhibited human cervical cancer xenograft growth without exhibiting toxicity in vivo. Conclusion Our findings highlight STAT3 as a promising therapeutic target. We also demonstrate that SNG is a novel anticancer drug for the treatment of cervical cancer.

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“…Before ex vivo and in vivo application, NC@PDA-NH 2 was dispersed in Pluronic F127-based thermosensitive hydrogel (FG) to avoid leakage which might happen if administered as a simple aqueous dispersion, and enough time was allowed for nanocrystals to interact with the mucosa. Other vehicles for nanoparticles were also reported for vaginal use, such as hydroxypropyl methylcellulose/poly(vinyl alcohol) films [31] and poly(vinyl alcohol) nanofibers [32]. FG was also applied as a vaginal formulation vehicle with good safety for many therapeutic agents.…”

Section: Resultsmentioning

confidence: 99%

Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer

Huang

et al. 2019

Pharmaceutics

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The present study was carried out to investigate the potential of cationic functionalization on imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion of cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH2) were prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential, and relatively high drug content with the aid of the polydopamine-coating technique. Efficient interaction between NC@PDA-NH2 and mucin was proven by mucin adsorption which was related to the positive zeta-potential value of NC@PDA-NH2 and the change in the size distribution on mixing of NC@PDA-NH2 and mucin. Cellular uptake, growth inhibition, and apoptosis induction in cervicovaginal cancer-related cells demonstrated the superiority of NC@PDA-NH2 over unmodified nanocrystals. For practical intravaginal administration, NC@PDA-NH2 was dispersed in Pluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature and sustained-release profiles. In comparison with unmodified nanocrystals, NC@PDA-NH2 exhibited extended residence on ex vivo murine vaginal mucosa, prolonged in vivo intravaginal residence, and enhanced inhibition on the growth of murine orthotopic cervicovaginal model tumors indicated by smaller tumor size, longer median survival time, and more intratumor apoptosis with negligible mucosal toxicity. In conclusion, cationic functionalization endowed NC@PDA-NH2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer via intravaginal administration.

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Preparation and in vitro evaluation of vaginal formulations including siRNA and paclitaxel-loaded SLNs for cervical cancer

Cited by 50 publications

References 51 publications

Clarithromycin-Loaded Poly (Lactic-co-glycolic Acid) (PLGA) Nanoparticles for Oral Administration: Effect of Polymer Molecular Weight and Surface Modification with Chitosan on Formulation, Nanoparticle Characterization and Antibacterial Effects

Clarithromycin-Loaded Poly (Lactic-co-glycolic Acid) (PLGA) Nanoparticles for Oral Administration: Effect of Polymer Molecular Weight and Surface Modification with Chitosan on Formulation, Nanoparticle Characterization and Antibacterial Effects

<p>Sanguinarine exhibits potent efficacy against cervical cancer cells through inhibiting the STAT3 pathway in vitro and in vivo</p>

Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer

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