Improved oral bioavailability and brain transport of Saquinavir upon administration in novel nanoemulsion formulations

Vyas, Tushar K.; Shahiwala, Aliasgar; Amiji, Mansoor M.

doi:10.1016/j.ijpharm.2007.06.016

Cited by 231 publications

(103 citation statements)

References 25 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[24][25][26][27] It has been also reported that intranasal administration of micro/nanoemulsions could have a brain-targeting effect. [28][29][30][31][32][33][34][35][36][37] In the present study, we confirmed that a CLA-PTX microemulsion administered intravenously could also produce antitumor activity in brain tissue.…”

Section: Discussionsupporting

confidence: 84%

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Li¹,

Yang²,

Li³

et al. 2012

IJN

View full text Add to dashboard Cite

Background: Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood-brain barrier, but has poor water solubility, the purpose of this study was to prepare a novel CLA-PTX microemulsion and evaluate its activity against brain tumors in vitro and in vivo. Methods: The in vitro cytotoxicity of a CLA-PTX microemulsion was investigated in C6 glioma cells. The in vivo antitumor activity of the CLA-PTX microemulsion was evaluated in tumorbearing nude mice and rats. The pharmacokinetics of the CLA-PTX microemulsion were investigated in rats, and its safety was also evaluated in mice. Results: The average droplet size of the CLA-PTX microemulsion was approximately 176.3 ± 0.8 nm and the polydispersity index was 0.294 ± 0.024. In vitro cytotoxicity results showed that the IC 50 of the CLA-PTX microemulsion was 1.61 ± 0.83 µM for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P . 0.05). The antitumor activity of the CLA-PTX microemulsion against brain tumors was confirmed in our in vivo C6 glioma tumor-bearing nude mice as well as in a rat model. In contrast, Taxol ® had almost no significant antitumor effect in C6 glioma tumor-bearing rats, but could markedly inhibit growth of C6 tumors in C6 glioma tumor-bearing nude mice. The pharmacokinetic results indicated that CLA-PTX in solution has a much longer circulation time and produces higher drug plasma concentrations compared with the CLA-PTX microemulsion. The results of the acute toxicity study showed that the LD 50 of CLA-PTX solution was 103.9 mg/kg. In contrast, the CLA-PTX microemulsion was well tolerated in mice when administered at doses up to 200 mg/kg. Conclusion: CLA-PTX microemulsion is a novel formulation with significant antitumor efficacy in the treatment of brain tumors, and is safer than CLA-PTX solution.

show abstract

Section: Discussionsupporting

confidence: 84%

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Li¹,

Yang²,

Li³

et al. 2012

IJN

View full text Add to dashboard Cite

show abstract

“…46,47 Several lipid based formulations such as saquinavir (Fortovase®, Roche Pharmaceuticals, NJ, USA), ritonavir (Norvir®, Abbott Laboratories, IL, USA), cyclosporin (Neoral®, Novartis Pharmaceutical Ltd., Surrey, UK) were approved by regulatory agencies and given impetus for development of lipid based formulations for the improved oral delivery of poorly water soluble drugs. Nanoemulsion drug delivery have been reported to improve the bioavailability of hydrophobic drugs very effectively 53,54 , increased in vivo performance of anticancer drugs, e.g., dacarbazine 55 and camptothecin. 56 In our present study, we have formulated RST and KT nanoemulsions as a carrier for new DDX3 helicase inhibitor.…”

Section: Discussionmentioning

confidence: 99%

In vitro Anti-Cancer Activity of Rosuvastatin and Ketorolac Nanoformulations against DDX3

Bheemanapally¹,

Thimmaraju²,

Kasagoni³

et al. 2017

JYP

View full text Add to dashboard Cite

INTRODUCTIONHuman DDX3 gene encodes a polypeptide of 662 amino acids and this protein plays an important role in several aspects of RNA metabolism. 1,2 This protein has two clear distinguishable domains comprised of N-terminal DEAD box domain 1 (211-403 residues) and C-terminal helicase domain 2 (411-575 residues). Both domains displayed RecA-like folds comprising a central β-sheet flanked by α-helices connected by a noncanonical linker of 11 amino acids.3 Expression of DDX3 was detected in several tissues such as testis, colon, lung, liver, skeletal muscle, and kidney 2,4 indicating the universal role of DDX3 in cellular homeostasis. Moreover, elevated expression of DDX3 was found in a highly aggressive metastatic breast cancer cell line, MDA-MB-231, as compared with non-metastatic MCF-7 cells, which show its potential role in aggressive breast cancers and associated metastasis. 5,6 We have previously reported that overexpression of DDX3 in immortalized non-turmorigenic MCF10A cells promoted neoplastic transformation as indicated by down regulation of a cell adhesion molecule, E-cadherin.5 Down-regulation of E-cadherin is a common feature of a variety of metastatic epithelial tumors, including those of the lung, breast and prostate cancer.5,7-9 Hypoxic regions of solid tumors were considered to be the primary sites for the generation of the metastatic phenotype and have been demonstrated to be chemo and radio-resistant. [10][11][12][13][14] We have also reported that hypoxia inducible factor (HIF-1) induce the expression of DDX3 in two different breast cell lines by binding directly or indirectly to the hypoxia-response element (HRE) in the DDX3 proximal promoter. 15 On the other hand, a significant down regulation of DDX3 expression is found in hepatocellular carcinoma (HCCs) from the hepatitis B virus (HBV) positive patients, but not from HCV positive in comparison to the corresponding non tumor tissues. 16 In the hepatocellular carcinoma model, DDX3 was found to act as a tumor suppressor by activating the expression of cyclin dependent kinase inhibitor p21 cip1 . 17 Besides cancer, induced expression of DDX3 was also found in HIV-1 infected cells. 18,19 Overall, it suggests that DDX3 is a multifunctional protein and it plays a specific role in regulatory mechanisms and signaling pathways. Apart from embryonic development, this gene is also involved in multiple diseases like HIV, Neuro-degenerative diseases, hepatocellular carcinoma and brain and breast cancer. Several Synthetic compounds have been discovered to inhibit the function of DDX3 by blocking the function of helicase activity. [20][21][22][23][24] Synthetic drugs are those substances that are produced entirely from chemical reactions in a laboratory. Synthetic drugs most often have shown to suppress the immune system by paralyzing the bone marrow. 25,26 Moreover, it takes an average of about 8 to 12 years from the time a cancer drug enters into clinical trials from the research lab.27,28 Therefore, we focused to identify FDA approved drugs against D...

show abstract

“…Mucoadhesive MEs could further enhance nose to brain targeting through improved residence time (Vyas et 2006a, 2006bJogani et al, 2008). The high brain delivery of saquinavir, an anti-HIV drug following oral administration of an ME containing flaxseed oil was attributed to docosahexaenoic acid (DHA)-mediated bypass of the BBB (Vyas et al, 2008). Moreover, DHA as a brain nutrient could provide additional advantage.…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic acid–mediated, targeted and sustained brain delivery of curcumin microemulsion

Shinde

Devarajan

2017

Drug Delivery

View full text Add to dashboard Cite

We disclose microemulsions (ME) of curcumin (CUR) with docosahexaenoic acid (DHA)-rich oil (CUR DHA ME) for targeted delivery to the brain. MEs of CUR (5 mg/mL) with and without DHArich oil (CUR Capmul ME) suitable for intravenous and intranasal administration exhibited negative zeta potential, globule size 520 nm and good stability. Following intravenous delivery MEs exhibited high brain concentration with CUR DHA ME exhibiting a 2.8-fold higher C max than CUR solution. Furthermore, high and sustained concentration was demonstrated even at 24 h, which was 8-and 2-fold higher than CUR solution and CUR Capmul ME, respectively. Brain concentrations following intranasal administration were, however, substantially higher as evident from higher C max and AUC and sustained compared to corresponding intravenous formulations signifying nose to brain targeting. The high brain concentration of CUR DHA ME is ascribed to the targeting efficiency enabled by DHA-mediated transport across the blood-brain barrier (BBB). Histopathological and nasal toxicity confirmed safety of the MEs. Concentrationdependent cytotoxicity in vitro, on human glioblastoma U-87MG cell line was observed with CUR DHA MEs and with the blank DHA ME, implying anticancer potential of DHA. The dramatically low IC 50 value of CUR DHA ME (3.755 ± 0.24 ng/mL) is therefore attributed to the synergistic effect of CUR and DHA in the ME. The CUR concentration achieved with CUR DHA ME at 24 h which translated to 466-fold(intranasal) and 421-fold (intravenous) the IC 50 value in the U-87MG cell line suggests great promise of CUR DHA ME for therapy of brain cancer by both routes.

show abstract

Improved oral bioavailability and brain transport of Saquinavir upon administration in novel nanoemulsion formulations

Cited by 231 publications

References 25 publications

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

In vitro Anti-Cancer Activity of Rosuvastatin and Ketorolac Nanoformulations against DDX3

Docosahexaenoic acid–mediated, targeted and sustained brain delivery of curcumin microemulsion

Contact Info

Product

Resources

About