Alpha-lipoic acid–stearylamine conjugate-based solid lipid nanoparticles for tamoxifen delivery: formulation, optimization, in-vivo pharmacokinetic and hepatotoxicity study

Dhaundiyal, Ankit; Jena, Sunil Kumar; Samal, Sanjaya K.; Sonvane, Bhavin; Chand, Mahesh; Sangamwar, Abhay T.

doi:10.1111/jphp.12644

Cited by 25 publications

(10 citation statements)

References 38 publications

(81 reference statements)

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“…However, body weight loss was still observed in treated rats as compared to controls. Dhaundiyal and collaborators designed poly (lactic- co -glycolic acid) Tam NPs that showed increased bioavailability and a milder effect on body weight [44]. Our in vivo homing results show selective targeting of iRGD-PS-Tam to the tumor and very little accumulation in non-malignant tissues.…”

Section: Discussionmentioning

confidence: 80%

“…However, the accumulation of Tam in other organs remained the same and therapeutic response was not significantly improved as compared to the non-targeted NPs [43]. In another study, Tam was vehiculized in alpha-lipoic acid–stearylamine conjugate-based solid lipid NPs [44]. In this case bioavailability was increased and hepatotoxicity was partially decreased.…”

Section: Discussionmentioning

confidence: 99%

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iRGD-guided tamoxifen polymersomes inhibit estrogen receptor transcriptional activity and decrease the number of breast cancer cells with self-renewing capacity

et al. 2019

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BackgroundTamoxifen (Tam) is the most frequent treatment for estrogen receptor (ER) positive breast cancer. We recently showed that fibronectin (FN) leads to Tam resistance and selection of breast cancer stem cells. With the aim of developing a nanoformulation that would simultaneously tackle ER and FN/β1 integrin interactions, we designed polyethylene glycol-polycaprolactone polymersomes polymersomes (PS) that carry Tam and are functionalized with the tumor-penetrating iRGD peptide (iRGD-PS-Tam).ResultsPolyethylene glycol-polycaprolactone PS were assembled and loaded with Tam using the hydration film method. The loading of encapsulated Tam, measured by UPLC, was 2.4 ± 0.5 mol Tam/mol polymer. Physicochemical characterization of the PS demonstrated that iRGD functionalization had no effect on morphology, and a minimal effect on the PS size and polydispersity (176 nm and Pdi 0.37 for iRGD-TAM-PS and 171 nm and Pdi 0.36 for TAM-PS). iRGD-PS-Tam were taken up by ER+ breast carcinoma cells in 2D-culture and exhibited increased penetration of 3D-spheroids. Treatment with iRGD-PS-Tam inhibited proliferation and sensitized cells cultured on FN to Tam. Mechanistically, treatment with iRGD-PS-Tam resulted in inhibition ER transcriptional activity as evaluated by a luciferase reporter assay. iRGD-PS-Tam reduced the number of cells with self-renewing capacity, a characteristic of breast cancer stem cells. In vivo, systemic iRGD-PS-Tam showed selective accumulation at the tumor site.ConclusionsOur study suggests iRGD-guided delivery of PS-Tam as a potential novel therapeutic strategy for the management of breast tumors that express high levels of FN. Future studies in pre-clinical in vivo models are warranted.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

iRGD-guided tamoxifen polymersomes inhibit estrogen receptor transcriptional activity and decrease the number of breast cancer cells with self-renewing capacity

et al. 2019

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“…Tamoxifen has often been administered orally to patients. There has been some research focusing on the drug-delivery system of tamoxifen nanoparticles 54,55. However, there have been no reports on the formulation of tamoxifen to maintain the drug in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>A temperature-sensitive phase-change hydrogel of tamoxifen achieves the long-acting antitumor activation on breast cancer cells</p>

Du¹,

Lei²,

Zheng³

et al. 2019

OTT

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Background: Breast cancer is one of the foremost threats to female health nowadays. Tamoxifen, an antagonist of estrogen receptor-α (ERα), is the first choice for endocrine-dependent breast cancer (ERα-positive breast cancer) treatment. However, ERα has an important function in the normal physical regulation of estrogen, and current oral administration of tamoxifen has potential side effects on normal endocrine secretion. In the present work, we aim to develop novel approaches to increase the antitumor effect of tamoxifen on breast cancer cells and decrease the potential side effects in the human body during treatment. Methods: A temperature-sensitive phase-change hydrogel for tamoxifen (Tam-Gel) was generated. After establishing subcutaneous tumors formed by MCF-7, an ERα-positive breast cancer cell line, in nude mice, an intratumoral injection of Tam-Gel was performed to examine whether Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. A metastatic breast cancer model was established using the intrahepatic growth of MCF-7 cells in immunodeficient rats. Results: Tam-Gel can transform from liquid to hydrogel at room temperature. An intratumoral injection of Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. Once Tam-Gel, but not Tam-Sol, was administered by intratumoral injection, it significantly decreased the uptake of radionuclide probes ( 18 F-fluoroestradiol or 18 F-fluorodeoxyglucose) by cells in rats’ livers and the intrahepatic growth of MCF-7 cells in rats’ livers. Conclusion: A novel slow-release system was successfully prepared to facilitate the long-term release of tamoxifen in breast cancer tissues, and achieved an antitumor effect in the long term.

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“…The obtained emulsion was then mixed with water to form SLNs, and the organic solvent was removed using a rotary evaporator under reduced pressure. Of three solvents screened (ethyl acetate, n-propyl acetate, and isopropyl acetate), SLNs prepared with isopropylacetate were the optimal formulation with a PS of 233 nm and a PDI of 0.114 [ 87 ]. In a recent study, letrozole-loaded SLNs were prepared using this method, although mutual saturation of solvent and water was not required.…”

Section: Methods For Slns and Nlcs Preparationmentioning

confidence: 99%

Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Drug Delivery and the Effects of Preparation Parameters of Solvent Injection Method

2020

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Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have emerged as potential drug delivery systems for various applications that are produced from physiological, biodegradable, and biocompatible lipids. The methods used to produce SLNs and NLCs have been well investigated and reviewed, but solvent injection method provides an alternative means of preparing these drug carriers. The advantages of solvent injection method include a fast production process, easiness of handling, and applicability in many laboratories without requirement of complicated instruments. The effects of formulations and process parameters of this method on the characteristics of the produced SLNs and NLCs have been investigated in several studies. This review describes the methods currently used to prepare SLNs and NLCs with focus on solvent injection method. We summarize recent development in SLNs and NLCs production using this technique. In addition, the effects of solvent injection process parameters on SLNs and NLCs characteristics are discussed.

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Alpha-lipoic acid–stearylamine conjugate-based solid lipid nanoparticles for tamoxifen delivery: formulation, optimization, in-vivo pharmacokinetic and hepatotoxicity study

Abstract: α-lipoic acid-stearylamine conjugate-based SLNs have a great potential in enhancing the oral bioavailability of poorly soluble drugs like TMX. Moreover, this ALA-SA nanoparticulate system could be of significant value in long-term anticancer therapy with least side effects.

Cited by 25 publications

References 38 publications

iRGD-guided tamoxifen polymersomes inhibit estrogen receptor transcriptional activity and decrease the number of breast cancer cells with self-renewing capacity

iRGD-guided tamoxifen polymersomes inhibit estrogen receptor transcriptional activity and decrease the number of breast cancer cells with self-renewing capacity

<p>A temperature-sensitive phase-change hydrogel of tamoxifen achieves the long-acting antitumor activation on breast cancer cells</p>

Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Drug Delivery and the Effects of Preparation Parameters of Solvent Injection Method

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