Enhancing Etoposide Aqueous Solubility and Anticancer Activity with L-Arginine

Alsalhi, Abdullah; Ayon, Navid J.; Coulibaly, Fohona S.; Alshamrani, Meshal; Alnafisah, Abrar S.; Youan, Bi‐Botti C.

doi:10.1089/adt.2021.085

Cited by 7 publications

(3 citation statements)

References 48 publications

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“…This suggests that co-administration of L -arginine with doxorubicin would be an effective treatment to enhance chemotherapy [ 64 ]. Many studies confirm the anticancer activity of arginine and often use it as an additive to enhance the effects of potential anticancer drugs [ 64 , 65 , 66 , 67 , 68 ]. In B. vulgaris , arginine-Bx ( 4 ) showed a strong effect on the RKO and HeLa cell lines; therefore, it may also be a potential anticancer drug candidate like L -alanine.…”

Section: Resultsmentioning

confidence: 99%

Betaxanthin Profiling in Relation to the Biological Activities of Red and Yellow Beta vulgaris L. Extracts

et al. 2023

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Beta vulgaris L. is an edible plant with health-beneficial activities. The profile of betaxanthins is more complex than previously described in beetroot cultivars. Twenty-four betaxanthins were detected in extracts of the peel and flesh of five cultivars by HPLC-DAD-ESI-MS, of which two new betaxanthins (arginine-Bx and ornithine-Bx) were detected for the first time in B. vulgaris cultivars. The content of betaxanthins in the studied cultivars decreased in the Tytus > Ceryl > Chrobry > Forono > Boldor sequence. The highest content of compounds (1231 mg/100 g DE) was observed in the Tytus cultivar (peel). The peel of B. vulgaris, which is often considered a waste, appeared to be a richer source of betaxanthins compared to its flesh. Antibacterial and antifungal activities were determined against twenty-three microorganisms. Tytus (peel) showed a moderate or good bactericidal effect, especially against the majority of Gram-positive bacteria as well as against most of the tested fungi (MIC = 0.125–0.5 mg/mL) and additionally characterized by low cytotoxicity towards non-cancerous cells (CC50 = 405 μg/mL, CC50—50% cytotoxic concentration). Tytus flesh also showed a high cytotoxicity value against human cervical adenocarcinoma (HeLa), with CC50 of 282 μg/mL. Correlation analysis was used to determine the relationship between the betaxanthin profiles and antimicrobial and anticancer activities. Arginine-Bx, proline-Bx, and tryptophan-Bx were indicated as active against HeLa and the colon cancer cell line (RKO), while asparagine-Bx and phenylalanine-Bx was responsible for activity against all tested bacterial and yeast species. The significant effectiveness and safety of these beetroots make indicated compounds promising applicants as antimicrobial and anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Betaxanthin Profiling in Relation to the Biological Activities of Red and Yellow Beta vulgaris L. Extracts

et al. 2023

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“…Этопозид -полусинтетическое производное подофиллотоксина, ингибитор топоизомеразы II, который применяется в комбинированной химиотерапии РМЖ, а также рака яичников, немелкоклеточного рака легких, саркомы Капоши, лимфомы Ходжкина и опухолей головного мозга [3]. Этопозид обладает низкой растворимостью в воде (<0,1 мг/мл при +37 °С) [4], поэтому для получения его инъекционной формы используют высокие концентрации солюбилизаторов и сорастворителей (полисорбат-80, макрогол-300, бензиловый и этиловый спирты), способные вызвать реакции гиперчувствительности. Помимо известных примеров модификации молекулы этопозида (Etopophos®, фосфат этопозида), могут быть использованы другие стратегии повышения растворимости, в частности получение наносуспензий [5,6].…”

Section: Introductionunclassified

Development of Injectable Formulation of 4’-O-benzyloxycarbonyl-etoposide Derivative Based on Human Serum Albumin for the Chemotherapy of Breast Cancer

Kovshova,

Boiko,

Merkulova

et al. 2023

Razrabotka i registraciâ lekarstvennyh sredstv

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Introduction. One of the promising strategies for the development of injectable formulations of poorly water-soluble drugs is the preparation of their nanosuspensions stabilized with albumin. A well-known example of the successful implementation of this technology is Abraxane® (nanoparticle albumin-bound paclitaxel). In the present study, this approach is used for the development of the injectable formulation of a hydrophobic etoposide prodrug.Aim. Development of the injectable formulation of a novel 4'-О-benzyloxycarbonyl derivative of etoposide (ETP-cbz) based on human serum albumin and evaluation of its cytotoxicity against breast carcinoma cells (BC).Materials and methods. The structure of ETP-cbz was confirmed by NMR spectroscopy and elemental analysis; log P was calculated in silico using Molinspiration Cheminformatics. The ETP-cbz-HSA nanoparticles were prepared by high pressure homogenization. The particle size, size distribution, and disintegration concentration were evaluated by dynamic light scattering (DLS) and atomic force microscopy (AFM). The contents of ETP-cbz and albumin in the formulation were determined by HPLC. The conversion ETP-cbz-HSA to etoposide was studied in a model medium in the presence of esterase. The cytotoxicity of ETP-cbz-HSA compared to etoposide and free ETP-cbz was assessed on BC cells (HBL-100 and MCF-7) using a colorimetric MTT assay.Results and discussion. ETP-cbz exhibited higher hydrophobicity as compared to the etoposide (log P 2.42 vs 0.7, respectively). Due to easy cleavage of the carbonate bond in the presence of esterase, ETP-cbz can be considered an etoposide prodrug. The ETP-cbz-containing HSA nanoparticles prepared by a high-pressure homogenization technique had the particle size of 110 ± 9 nm (DLS) and a low disintegration concentration of 3.0 ± 0.1 μg/mL. The drug content was 1.75 mg/mL. The nanoformulation demonstrated high cytotoxic activity in vitro against MCF-7 and HBL-100 cells that was comparable to the activity of substances etoposide and ETP-cbz.Conclusion. The obtained nanoformulation of etoposide prodrug based on albumin, suitable for injection, showed high cytotoxicity against breast cancer cells in vitro and deserves further study to assess the possibility of its use in breast cancer chemotherapy.

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“…To maintain the therapeutic level of DTX in the system, higher doses are required, which cause severe systemic toxicity and develops cancer resistance [10]. It has been reported that approximately 40% of the medications on the market and 90% of the medications under production have low aqueous solubility [11]. Common solubility enhancing agents, such as Tween-80 and Cremophor EL, can enhance the aqueous solubility of hydrophobic drugs; however, such excipients can cause severe adverse effects in humans [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Self-Assembled Nanomicellar Formulation of Docetaxel as a Potential Breast Cancer Chemotherapeutic System

Alshamrani

Ayon

Alsalhi

et al. 2022

Life

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Docetaxel (DTX) is classified as a class IV drug that exhibits poor aqueous solubility (6–7 µg/mL in water) and permeability (P-glycoprotein substrate). The main objective of this study was to construct, characterize, and evaluate docetaxel loaded nanomicellar formulation in vitro for oral delivery to enhance the absorption and bioavailability of DTX, as well as to circumvent P-gp efflux inhibition. Formulations were prepared with two polymeric surfactants, hydrogenated castor oil-40 (HCO-40) and D-α-Tocopherol polyethylene glycol 1000 succinate (VIT E TPGS) with solvent evaporation technique, and the resulting DTX nanomicellar formulations were characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier Transform Infrared Spectroscopy (FT–IR), X-ray powder diffraction (XRD), and transmission electron microscopy (TEM). Proton NMR, FT–IR, and XRD data indicated that DTX was completely encapsulated within the hydrophobic core of the nanomicelles in its amorphous state. TEM data revealed a smooth spherical shape of the nanomicellar formulation. The optimized formulation (F-2) possessed a mean diameter of 13.42 nm, a zeta potential of −0.19 mV, with a 99.3% entrapment efficiency. Dilution stability study indicated that nanomicelles were stable up to 100-fold dilution with minimal change in size, poly dispersity index (PDI), and zeta potential. In vitro cytotoxicity study revealed higher anticancer activity of DTX nanomicelles at 5 µM compared to the native drug against breast cancer cell line (MCF-7) cells. The LC–MS data confirmed the chemical stability of DTX within the nanomicelles. In vitro drug release study demonstrated faster dissolution of DTX from the nanomicelles compared to the naked drug. Our experimental results exhibit that nanomicelles could be a drug delivery system of choice to encapsulate drugs with low aqueous solubility and permeability that can preserve the stability of the active constituents to provide anticancer activity.

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Enhancing Etoposide Aqueous Solubility and Anticancer Activity with L-Arginine

Cited by 7 publications

References 48 publications

Betaxanthin Profiling in Relation to the Biological Activities of Red and Yellow Beta vulgaris L. Extracts

Betaxanthin Profiling in Relation to the Biological Activities of Red and Yellow Beta vulgaris L. Extracts

Development of Injectable Formulation of 4’-O-benzyloxycarbonyl-etoposide Derivative Based on Human Serum Albumin for the Chemotherapy of Breast Cancer

Self-Assembled Nanomicellar Formulation of Docetaxel as a Potential Breast Cancer Chemotherapeutic System

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