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In recent decades, there has been a continuous rise in the worldwide demand for electrochemical electrodes, driven by their established advantages such as rapidity, costeffectiveness, user-friendly nature, and practicality in comparison to alternative electrochemical methods. However, despite these advancements, there remains a pressing need to tailor electrode preparation methods to accommodate the diverse requirements of the pharmaceutical industry. A newly developed electrochemical method was described to produce three stable probes to measure tamoxifen citrate by a coated protective layer formed from ZnO nanocomposite polymer. This modified layer was prepared by drop-casting a solution of ethaline: oxaline: water on a polymer membrane. The modified membrane exhibited potential by less than 0.22 mV for 24 days. Different analytical measurements were examined to determine the optimization proposed electrode; it was found that the addition of polymer nanocomposite metals polymer mixed with deep eutectic solvents prompted high probe efficiency used for poor solubility drugs in water . The Nernstian slope was found to be good agreement measurements in Polyvinyl Pyrrolidine (PVP) electrode around 59.71±0.60 mV/decade while other electrodes slightly decreased at 58.88±0.23 mV/decade for Poly Ethylene Glycol (PEG) and 60.20±0.15 mV/decade recorded for polyvinylchloride (PVC) electrode. Tamoxifen samples in tablet form were found to be acceptable and accurate determinations in new electrochemical technique dependent on the preparation of different nanocomposite ZnO polymer molecules, with trace added of (1.5%, 2.0%, and 2.5%) weight percentage deep eutectic solvent water mixtures (DESs) as supporting permeation during hydrophobic membranes attributed to partition and pores mechanisms helped to ion pair diffusion. [ABSTRACT FROM AUTHOR]

Background: Drug combination therapy is preferred over monotherapy in clinical research to improve therapeutic effects. Developing a new nanodelivery system for cancer drugs can reduce side effects and provide several advantages, including matched pharmacokinetics and potential synergistic activity. This study aimed to examine and determine the efficiency of the gemini surfactants (GSs) as a pH-sensitive polymeric carrier and cell-penetrating agent in cancer cells to achieve dual drug delivery and synergistic effects of curcumin (Cur) combined with tamoxifen citrate (TMX) in the treatment of MCF-7 and MDA-MB-231 human BC cell lines. Methods: The synthesized NPs were self-assembled using a modified nanoprecipitation method. The functional groups and crystalline form of the nanoformulation were examined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) used to assess zeta potential and particle size, and the morphological analysis determined by transmission electron microscopy (TEM). The anticancer effect was evaluated through an in vitro cytotoxicity MTT assay, flow cytometry analysis, and apoptosis analysis performed for mechanism investigation. Results: The tailored NPs were developed with a size of 252.3 ± 24.6 nm and zeta potential of 18.2 ± 4.4 mV capable of crossing the membrane of cancer cells. The drug loading and release efficacy assessment showed that the loading of TMX and Cur were 93.84% ± 1.95% and 90.18% ± 0.56%, respectively. In addition, the drug release was more controlled and slower than the free state. Polymeric nanocarriers improved controlled drug release 72.19 ± 2.72% of Tmx and 55.50 ± 2.86% of Cur were released from the Tmx-Cur-Gs NPs after 72 h at pH = 5.5. This confirms the positive effect of polymeric nanocarriers on the controlled drug release mechanism. moreover, the toxicity test showed that combination-drug delivery was much more greater than single-drug delivery in MCF-7 and MDA-MB-231 cell lines. Cellular imaging showed excellent internalization of TMX-Cur-GS NPs in both MCF-7 and MDA-MB-231 cells and synergistic anticancer effects, with combination indices of 0.561 and 0.353, respectively. Conclusion: The combined drug delivery system had a greater toxic effect on cell lines than single-drug delivery. The synergistic effect of TMX and Cur with decreasing inhibitory concentrations could be a more promising system for BC-targeted therapy using GS NPs. [ABSTRACT FROM AUTHOR]

Abstract Background Drug combination therapy is preferred over monotherapy in clinical research to improve therapeutic effects. Developing a new nanodelivery system for cancer drugs can reduce side effects and provide several advantages, including matched pharmacokinetics and potential synergistic activity. This study aimed to examine and determine the efficiency of the gemini surfactants (GSs) as a pH-sensitive polymeric carrier and cell-penetrating agent in cancer cells to achieve dual drug delivery and synergistic effects of curcumin (Cur) combined with tamoxifen citrate (TMX) in the treatment of MCF-7 and MDA-MB-231 human BC cell lines. Methods The synthesized NPs were self-assembled using a modified nanoprecipitation method. The functional groups and crystalline form of the nanoformulation were examined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) used to assess zeta potential and particle size, and the morphological analysis determined by transmission electron microscopy (TEM). The anticancer effect was evaluated through an in vitro cytotoxicity MTT assay, flow cytometry analysis, and apoptosis analysis performed for mechanism investigation. Results The tailored NPs were developed with a size of 252.3 ± 24.6 nm and zeta potential of 18.2 ± 4.4 mV capable of crossing the membrane of cancer cells. The drug loading and release efficacy assessment showed that the loading of TMX and Cur were 93.84% ± 1.95% and 90.18% ± 0.56%, respectively. In addition, the drug release was more controlled and slower than the free state. Polymeric nanocarriers improved controlled drug release 72.19 ± 2.72% of Tmx and 55.50 ± 2.86% of Cur were released from the Tmx-Cur-Gs NPs after 72 h at pH = 5.5. This confirms the positive effect of polymeric nanocarriers on the controlled drug release mechanism. moreover, the toxicity test showed that combination-drug delivery was much more greater than single-drug delivery in MCF-7 and MDA-MB-231 cell lines. Cellular imaging showed excellent internalization of TMX-Cur-GS NPs in both MCF-7 and MDA-MB-231 cells and synergistic anticancer effects, with combination indices of 0.561 and 0.353, respectively. Conclusion The combined drug delivery system had a greater toxic effect on cell lines than single-drug delivery. The synergistic effect of TMX and Cur with decreasing inhibitory concentrations could be a more promising system for BC-targeted therapy using GS NPs.

The objective of this study was to develop folic acid (FA) grafted mixed polymeric micelles loaded with Tamoxifen citrate (TMXC) to enhance its antitumor activity in breast tissues. The conjugated folic acid Pluronic 123 (FA-P123) was prepared using carbonyl diimidazole cross-linker chemistry and confirmed using FTIR and 1HNMR. TMXC-loaded P123/P84 (unconjugated) and TMXC-loaded FA-P123/P84 (conjugated) micelles were examined for encapsulation efficiency, particle size, surface charge, in vitro drug release, cytotoxic effect, and cellular uptake by a breast cancer cell line. The conjugated TMXC-loaded micelle exhibited a nanoparticle size of 35.01 ± 1.20 nm, a surface charge of—20.50 ± 0.95 mV, entrapped 87.83 ± 5.10% and released 67.58 ± 2.47% of TMXC after 36 h. The conjugated micelles exhibited a significantly higher cellular uptake of TMXC by the MCF-7 cell line and improved in vitro cytotoxicity by 2.48 folds compared to the TMXC-loaded unconjugated micelles. The results of in vivo studies indicated that TMXC-loaded FA-P123/P84 has a potential antitumor activity, as revealed by a significant reduction of tumor volume in tumor-bearing mice compared to TMXC-loaded unconjugated micelles. In conclusion, the obtained results suggested that conjugated FA-P123/P84 micelles could be an encouraging carrier for the treatment of breast cancer with TMXC. [ABSTRACT FROM AUTHOR]

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Tamoxifen citrate (TC) is one of the anti-estrogen agents which has low solubility in the water. As TC is still used as the main therapy in breast cancer treatment, modifications are still being made to increase the solubility of TC for a successful treatment. In this research, co-crystallization of TC was performed using Nicotinamide (NIC), Isonicotinamide (ISO), Saccharin (SAC), Aspartame (ASP), and Benzoic Acid (BNZ) as a coformer with the molar ratio of 1:1, 1:2, and 2:1. Co-crystal was prepared by solvent drop grinding (SDG) and solvent evaporation (SE) methods using methanol. The results of the solubility test showed that TC-NIC and TC-ISO co-crystals with a 1:2 molar ratio made using the SDG and SE methods gave the best results. Meanwhile, the best dissolution test results were shown by TC-ISO co-crystals with a ratio of 1:2. Based on the characterization of physical stability, the SDG method resulted in more stable TC co-crystals than the SE method. Therefore, in this case, the SDG method could be more advantageous to be used for development in the field of co-crystallization.

Objective: The purpose of the present study is to evaluate the transfersomal gel formulation for transdermal delivery of Tamoxifen citrate by DOE Approach. Materials and Methods: Transferosomes are ultra-flexible supra-molecular aggregates with a great ability to permeate intact mammalian skin.The formulation were designed by Box-Behnkenn Design. For usage as a transferosomal gel, drug encapsulation in various transfersomal formulations having various ratios of different drug concentrations (0.05, 0.1, 0.2, 0.3, 0.4, 0.5 g) and Carbopol-940-934 (0.5,1.2 g) is being studied. Results: Entrapment efficiency (EE percent), drug content, in-vitro skin penetration testing, and stability studies were all found in the produced formulations. Transmission Electron Microscopy confirmed that the vesicles were spherical in shape. According to the findings, tamoxifen citrate was effectively pinned with a standardised drug concentration in all formulations. The 0.1 g Tamoxifen citrate optimised transferosome formulation MG2 exhibited encouraging results, with maximum drug release (94.32%) and maximum drug release (94.32%), respectively (94.32%). Conclusion: Transferosomes, according to this study, are a promising long-term delivery route for Tamoxifen citrate and are relatively stable. This research reveals that transferosomes containing Tamoxifen citrate could be used to treat squamous cell carcinoma via transdermal drug delivery. [ABSTRACT FROM AUTHOR]

The present study aims to design and develop a nanoemulgel formulation of Tamoxifen citrate (TAM), a water-insoluble, potent anticancer drug, using the spontaneous emulsification method to improve topical delivery, achieve high accumulation at the tumour site, and spare the healthy tissues. The oil-based selection was related to the TAM solubility, while the surfactant and co-surfactant were chosen based on the droplets' thermodynamic stability and size. Afterwards, a pseudo-ternary phase diagram was built for the most promising formulation using two oils, olive and sesame, with a varied mix of Tween 40 as the surfactant and Trascutol HP as the co-surfactant (Smix), by the optimisation of experiments. The nanoemulsion (NE) formulations that were prepared were found to have an average droplet size of 41.77 ± 1.23 nm and 188.37 ± 3.53 nm, with suitable thermodynamic stability and physicochemical properties. Both olive and sesame oils are natural food additives due to their associated antioxidant effects; therefore, they showed no toxicity profile on breast cell lines (MCF-7, ATCC number HTB-22). The TAM-NE preparations revealed a prolonged and doublings superior cumulative percentage of in vitro release of TAM compared to TAM plain gel suspension over 24 h. The release data suggested that the Higuchi model was the best fitting kinetical model for the developed formulations of NE1, NE9, and NE18. The extended release of the drug as well as an acceptable amount of the drug permeated TAM via nanogel preparations suggested that nanoemulgel (NEG) is suitable for the topical delivery of TAM in breast cancer management. Thus, this work suggests that a nanogel of TAM can improve anticancer properties and reduce systemic adverse effects compared to a suspension preparation of TAM when applied in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery is the transport of drug across the skin and into the systemic circulation. Patch is a one of transdermal device that is used to attach on skin and contains drug. The drug matrices from hyaluronic acid (HA) and graphene oxide (GO) incorporated HA hydrogel were fabricated for the release of tamoxifen citrate (TMX) as the anticancer drug under applied electrical field. The pristine HA hydrogels as the matrix and GO as the drug encapsulation host were fabricated for transdermal patch by the solution casting using citric acid as the chemical crosslinker. In vitro drug release experiment was investigated by utilizing the modified Franz-diffusion cell under the effects of crosslinking ratio, electric potential, and GO. The TMX release behaviors from the hydrogels were found to be from the three mechanisms: the pure Fickian diffusion; the anomalous or non-Fickian diffusion; and Super case II transport depending on the crosslinking conditions. The TMX diffusion and release amount from the pristine HA hydrogels were increased with smaller crosslinking ratios. With applied electrical potential, the enhanced TMX diffusion and release amount were observed when compared to that without due to the electro-repulsive force. Furthermore, the TMX diffusion from the HA hydrogel with GO as the drug encapsulation host was higher by two orders of magnitude than without GO. [Display omitted] [ABSTRACT FROM AUTHOR]

Silk fibroin (SF) is a natural polymeric biomaterial that is widely adopted for the preparation of drug delivery systems. Herein, we aimed to fabricate and characterize SF nanoparticles loaded with the selective estrogen receptor modulator; tamoxifen citrate (TC-SF-NPs) and to assess their in vitro efficacy against breast cancer cell lines (MCF-7 and MDA-MB-231). TC-loaded SF-NPs were characterized for particle size, morphology, entrapment efficiency, and release profile. In addition, we examined the in vitro cytotoxicity of TC-SF-NPs against human breast cancer cell lines and evaluated the anticancer potential of TC-SF-NPs through apoptosis assay and cell cycle analysis. Drug-loaded SF-NPs showed an average particle size of 186.1 ± 5.9 nm and entrapment efficiency of 79.08%. Scanning electron microscopy (SEM) showed the nanoparticles had a spherical morphology with smooth surface. Tamoxifen release from SF-NPs exhibited a biphasic release profile with an initial burst release within the first 6 h and sustained release for 48 h. TC-SF-NPs exerted a dose-dependent cytotoxic effect against breast cancer cell lines. In addition, flow cytometry analysis revealed that cells accumulate in G0/G1 phase, with a concomitant reduction of S- and G2-M-phase cells upon treatment with TC-SF-NPs. Consequently, the potent anticancer activities of TC-SF-NPs against breast cancer cells were mainly attributed to the induction of apoptosis and cell cycle arrest. Our results indicate that SF nanoparticles may represent an attractive nontoxic nanocarrier for the delivery of anticancer drugs.

Silk fibroin (SF) is a natural polymeric biomaterial that is widely adopted for the preparation of drug delivery systems. Herein, we aimed to fabricate and characterize SF nanoparticles loaded with the selective estrogen receptor modulator; tamoxifen citrate (TC-SF-NPs) and to assess their in vitro efficacy against breast cancer cell lines (MCF-7 and MDA-MB-231). TC-loaded SF-NPs were characterized for particle size, morphology, entrapment efficiency, and release profile. In addition, we examined the in vitro cytotoxicity of TC-SF-NPs against human breast cancer cell lines and evaluated the anticancer potential of TC-SF-NPs through apoptosis assay and cell cycle analysis. Drug-loaded SF-NPs showed an average particle size of 186.1 ± 5.9nm and entrapment efficiency of 79.08%. Scanning electron microscopy (SEM) showed the nanoparticles had a spherical morphology with smooth surface. Tamoxifen release from SF-NPs exhibited a biphasic release profile with an initial burst release within the first 6 h and sustained release for 48 h. TC-SF-NPs exerted a dose-dependent cytotoxic effect against breast cancer cell lines. In addition, flow cytometry analysis revealed that cells accumulate in G0/G1 phase, with a concomitant reduction of S- and G2-M-phase cells upon treatment with TC-SF-NPs. Consequently, the potent anticancer activities of TC-SF-NPs against breast cancer cells were mainly attributed to the induction of apoptosis and cell cycle arrest. Our results indicate that SF nanoparticles may represent an attractive nontoxic nanocarrier for the delivery of anticancer drugs. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of death in women, and tamoxifen citrate (TMX) is accepted widely for the treatment of hormone receptor-positive breast cancers. Several local drug-delivery systems, including nanofibers, have been developed for antitumor treatment. Nanofibers are biomaterials that mimic the natural extracellular matrix, and they have been used as controlled release devices because they enable highly efficient drug loading. The purpose of the present study was to develop polycaprolactone (PCL) nanofibers incorporating TMX for use in the treatment of breast tumors. Pristine PCL and PCL-TMX nanofibers were produced by electrospinning and characterized physiochemically using different techniques. In addition, an in vitro study ofTMXrelease from the nanofibers was performed. The PCLTMX nanofibers showed sustained TMX release up to 14 h, releasing 100% of the TMX. The Resazurin reduction assay was used to evaluate the TMX cytotoxicity on MCF-7 breast cancer cell line and PBMCs human. The PCL-TMX nanofiber was cytotoxic toPBMCs and MCF-7. Based on these results, the PCL-TMX nanofibers developed have potential as an alternative for local chronic TMX use for breast cancer treatment, however tissue tests must be done. [ABSTRACT FROM AUTHOR]

Purpose: To develop a simple, novel, sensitive and rapid reverse phase high performance liquid chromatographic method for simultaneous determination of paclitaxel, sorafenib and omeprazole in standard solutions and spiked human plasma and its application to the in-vitro and in-vivo evaluation of paclitaxel polymeric nanoparticle formulations. Methods: The method was tested for the assessment of paclitaxel, omeprazole and sorafenib using tamoxifen citrate as internal standard. The analysis was performed at a wavelength of 235 nm using Thermo HS C18 column, 40 °C column oven temperature, acetonitrile and water (70:30 v/v, pH 3.37 adjusted with phosphoric acid) as a mobile phase and at a flow rate of 0.8 ml/min. All analytes were extracted by simple protein precipitation method using acetonitrile. The linearity was assessed in the concentration range of 1 - 2000 ng/mL for paclitaxel, omeprazole and sorafenib. Results: The developed chromatographic method effectively separated omeprazole, paclitaxel, sorafenib and IS with retention time of 3.93, 5.18, 6.43 and 9.93 min, respectively. The chromatograms of the three target compounds and IS showed good resolution and peak separation. The LOD of the method was 1, 5 and. 5 ng/mL while the LOQ was 2, 7.5 and 10 ng/mL, for paclitaxel, sorafenib and omeprazole, respectively. Conclusion: The proposed RP-HPLC–UV method for the assessment of paclitaxel, sorafenib and omeprazole in standard solutions and spiked plasma is simple, economical, sensitive and robust. The method is also suitable for the analysis of paclitaxel in nanoformulations and for its pharmacokinetic studies in an animal model. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of death in women, and tamoxifen citrate (TMX) is accepted widely for the treatment of hormone receptor–positive breast cancers. Several local drug-delivery systems, including nanofibers, have been developed for antitumor treatment. Nanofibers are biomaterials that mimic the natural extracellular matrix, and they have been used as controlled release devices because they enable highly efficient drug loading. The purpose of the present study was to develop polycaprolactone (PCL) nanofibers incorporating TMX for use in the treatment of breast tumors. Pristine PCL and PCL-TMX nanofibers were produced by electrospinning and characterized physiochemically using different techniques. In addition, an in vitro study of TMX release from the nanofibers was performed. The PCL-TMX nanofibers showed sustained TMX release up to 14 h, releasing 100% of the TMX. The Resazurin reduction assay was used to evaluate the TMX cytotoxicity on MCF-7 breast cancer cell line and PBMCs human. The PCL-TMX nanofiber was cytotoxic toPBMCs and MCF-7. Based on these results, the PCL-TMX nanofibers developed have potential as an alternative for local chronic TMX use for breast cancer treatment, however tissue tests must be done.

The present study aims to design and develop a nanoemulgel formulation of Tamoxifen citrate (TAM), a water-insoluble, potent anticancer drug, using the spontaneous emulsification method to improve topical delivery, achieve high accumulation at the tumour site, and spare the healthy tissues. The oil-based selection was related to the TAM solubility, while the surfactant and co-surfactant were chosen based on the droplets’ thermodynamic stability and size. Afterwards, a pseudo-ternary phase diagram was built for the most promising formulation using two oils, olive and sesame, with a varied mix of Tween 40 as the surfactant and Trascutol HP as the co-surfactant (Smix), by the optimisation of experiments. The nanoemulsion (NE) formulations that were prepared were found to have an average droplet size of 41.77 ± 1.23 nm and 188.37 ± 3.53 nm, with suitable thermodynamic stability and physicochemical properties. Both olive and sesame oils are natural food additives due to their associated antioxidant effects; therefore, they showed no toxicity profile on breast cell lines (MCF-7, ATCC number HTB-22). The TAM-NE preparations revealed a prolonged and doublings superior cumulative percentage of in vitro release of TAM compared to TAM plain gel suspension over 24 h. The release data suggested that the Higuchi model was the best fitting kinetical model for the developed formulations of NE1, NE9, and NE18. The extended release of the drug as well as an acceptable amount of the drug permeated TAM via nanogel preparations suggested that nanoemulgel (NEG) is suitable for the topical delivery of TAM in breast cancer management. Thus, this work suggests that a nanogel of TAM can improve anticancer properties and reduce systemic adverse effects compared to a suspension preparation of TAM when applied in the treatment of breast cancer.

The main intent of this treatise was to encapsulate tamoxifen citrate (TMXC) into polymeric micellar delivery system and evaluate the influence of TMXC-loaded micelles as a promising carrier on the in vitro cytotoxicity and cellular uptake of TMXC in treatment of breast cancer. Different formulae of polymeric micelles loaded with TMXC using mixtures of different Pluronic polymers were fabricated by thin-film hydration method and evaluated for morphology, drug entrapment efficiency, particle size, surface charge, in vitro liberation of TMXC, uptake by cancer cell lines, and cytotoxic effect against breast cancer cell lines such as MCF-7. The optimal TMXC-loaded micelles exhibited nano-sized particles and entrapped about 89.09 ± 4.2% of TMXC. In vitro liberation study revealed an extended TMXC escape of about 70.23 ± 5.9% over a period of 36 h. The optimized TMXC-loaded micelles formula showed enhanced cellular uptake of TMXC by 2.28 folds and showed a significant cytotoxic effect with MCF-7 breast cancer cells compared to TMXC solution. The obtained yield proposed that Pluronic micelles could be a promising potential delivery system for anticancer moieties. [ABSTRACT FROM AUTHOR]

Poor aqueous solubility is one of the key reasons for slow dissolution rate and poor intestinal absorption and finally that causes low therapeutic efficacy of many existing drugs. Tamoxifen citrate (TMX) (BCS Class II drug) with low water solubility has poor oral bioavailability in the range of 20%–30%, therefore, high doses are required for treatment with TMX. Self-assemblage of amphiphilic polymers leads to the formation of polymeric micelles which makes them unique nano-carriers with excellent biocompatibility, low toxicity, enhanced blood circulation time, and solubilization of poorly water-soluble drugs. In this study poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) triblock copolymer, which has been approved by FDA for oral application was used to benefit its micellar solubilization effect. Self-assembled micelles were prepared for the delivery of TMX and this way TMX solubility was increased approximately 60 times. TMX-treated cells showed 38.06 ± 1.5% viability at 50 µM concentration for 24 h; 66.71 ± 11.6% viability at 25 µM concentration for 48 h, at the same conditions TMX-loaded micelles exhibited 24.994 ± 0.25% and 43.36 ± 4.37% cell viability, respectively (p < 0.05). These results showed that the encapsulation of TMX into PEG-PPG-PEG micelles facilitated the cellular uptake, which led to an increased cytotoxicity in MCF-7 cancer cells. Tablet formulation containing lyophilized TMX-loaded micelles was showed an improved dissolution than commercial TMX tablet (Tamoxifen® TEVA). It can be reasonably expected that the obtained drug dissolution rate and increased cytotoxicity to tumor cells will result in an increase of TMX bioavailability and tolerability associated with an important dose reduction and decreased side effects. [ABSTRACT FROM AUTHOR]

The study was aimed to ameliorate the effect of Avena sativa seeds alcoholic extract and tamoxifen citrate on cadmium chloride (Cd) induced damage in rat testes. Avena sativa seeds was extracted and obtained 12% from extraction. Thirty male rats were divided into five groups and the period of treatment was 45 day. First group (C) were control negative group don't injected cd, second group (T1) was given Cd (2mg/kg) for one week and then treated with distilled water only, third group (T2) was given Cd (2mg/kg) for one week and then treated with Avena sativa seeds extract (226 mg/kg) orally, fourth group (T3) was given Cd (2mg/kg) for one week and then treated with tamoxifen citrate (1.767 mg/kg) and fifth group (T4) was given Cd (2mg/kg) I.P for one week and then treated by Avena sativa seeds extract (113 mg/kg) with tamoxifen citrate 0.88 mg/kg). The sperms count, motility and life sperms (T2) showed best significant increase with significant decrease in abnormalities percentage as compared with T1, T3 and T4 groups. The result of DNA damage in T2, showed significant decrease as compared with T2, T3 and T4, while the DNA damage in T4 showed a significant decrease as compared with T3. Third treated group (T2) showed best significant increase in testosterone, FSH and LH hormones concentration as compared with other treated groups. The SOD and GPX enzymes showed best significant increase in T2 and T4. Sections of rat testes in T1showed tissue damage with necrosis in seminiferous tubules, the testes in T2 showed best improvement in tissue with normal spermatocytes. Rat testes T3 showed reduction in spermatogenic and congestion of blood vessels, rat testes in T4 showed an improvement in testis tissue. This study, concluded that the alcoholic extract of Avena sativa seeds has protective role on fertility and reproductive organs of male laboratory rats against toxic effect of cadmium chloride. [ABSTRACT FROM AUTHOR]

Cancer is a group of diseases which include an abnormal increase in cell count, which may invade or spread into other parts of the body. One of the hallmarks of cancer is metastasis, which separates it from benign tumours. In case of breast cancer it may metastasize anywhere in the body. In the metastasis of breast cancer, inflammation or swelling with cancer cell generation can occur. In the present research, sustained release tablet containing tamoxifen citrate and ibuprofen is formulated which can be used in the treatment of metastasis of breast cancer. Tamoxifen citrate is an estrogen-blocker with potent antiestrogenic properties and Ibuprofen is a NSAID with antipyretic and analgesic effects being an inhibitor of cyclooxygenase. The combination tablet of Tamoxifen citrate and Ibuprofen with different HPMC grade polymers such as K35 M, E4 M and E10 M were formulated. The pre-formulation studies such as rest angle, bulk density, tapped density; the Hausner ratio and the Carr index were found to be within the normal limit. The absence of possible chemical reactions between the drug and polymers was suggested by FTIR spectra. Powder mixtures were compressed into tablets for weight variation, thickness, stiffness, friability and drug content evaluation after compression. The in vitro release of medicines was investigated for 12 hours with USP Type-II dissolution apparatus. Results showed that the drug release was maintained over 12 hours by formulations containing various polymers. [ABSTRACT FROM AUTHOR]

Cardiovascular side effects of broadly used chemotherapeutic drugs such as Tamoxifen citrate (TC), Capecitabine (CP) and Epirubicin (EP) among cancer survivors are well established. Nitric oxide (NO) is known to protect cardiovascular tissues under conditions of stress. NO can act through cyclic guanosine monophosphate (cGMP)‐dependent and ‐independent pathways. Particularly, the S‐nitrosylation of SH‐groups in a protein by NO falls under cGMP‐independent effects of NO. TC, CP, and EP are hypothesized as interfering with cellular protein S‐nitrosylation, which, in turn, may lead to endothelial dysfunctions. The results show that all three drugs attenuate nitrosylated proteins in endothelial cells. A significant reduction in endogenous S‐nitrosylated proteins was revealed by Saville–Griess assay, immunofluorescence and western blot. Incubation with the drugs causes a reduction in endothelial migration, vasodilation and tube formation, while the addition of S‐nitrosoglutathione (GSNO) has a reversal of this effect. In conclusion, results indicate the possibility of decreased cellular nitrosothiols as being one of the reasons for endothelial dysfunctions under TC, CP and EP treatment. Identification of the down‐regulated S‐nitrosylated proteins so as to correlate their implications on fundamental vascular functions could be an interesting phenomenon. [ABSTRACT FROM AUTHOR]

A series of aliphatic co-polyesters were prepared via one-step polycondensation reaction of itaconic acid, 1,4-cyclohexane dimethanol and diols using titanium tetraisopropoxide (TTIP) as a catalyst. The chemical structure of the repeating units present in the polymer chains were confirmed by FTIR, 1H and 13C NMR spectral data. The glass transition temperature (Tg), melting temperature (Tm) and decomposition temperature (Td) of the co-polyesters were evaluated by Differential Scanning Calorimetry (DSC). The biodegradability of the synthesized co-polyesters would be qualitatively studied by hydrolytic degradation at different pH followed by studying the change in surface morphology of the co-polyesters before and after degradation using Scanning Electron Microscope (SEM) images and the extent of crystallinity would also be studied using wide angle X-ray Diffraction (W-XRD) data. In-vitro anticancer activity of the synthesized co-polyesters were tested against human breast cancer (MCF-7) cell lines, all the co-polyesters show good IC50 value at lower concentration but among them PICMCD [Poly (1,4-cyclohexanedimethanol itaconate-co-1,4-cyclohexane diol itaconate)] has higher toxicity on MCF-7 cells. The drug delivery property of the co-polyesters would be investigated on tamoxifen citrate using spray down tablet coating process and PICMCD found to be a potential drug carrier. [ABSTRACT FROM AUTHOR]

Tamoxifen citrate (TMC), a non-steroidal antiestrogen drug used for the treatment of breast cancer, was loaded in a block copolymer of maltoheptaose-b-polystyrene (MH-b-PS) nanoparticles, a potential drug delivery system to optimize oral chemotherapy. The nanoparticles were obtained from self-assembly of MH-b-PS using the standard and reverse nanoprecipitation methods. The MH-b-PS@TMC nanoparticles were characterized by their physicochemical properties, morphology, drug loading and encapsulation efficiency, and release kinetic profile in simulated intestinal fluid (pH 7.4). Finally, their cytotoxicity towards the human breast carcinoma MCF-7 cell line was assessed. The standard nanoprecipitation method proved to be more efficient than reverse nanoprecipitation to produce nanoparticles with small size and narrow particle size distribution. Moreover, tamoxifen-loaded nanoparticles displayed spherical morphology, a positive zeta potential and high drug content (238.6 ± 6.8 µg mL−1) and encapsulation efficiency (80.9 ± 0.4 %). In vitro drug release kinetics showed a burst release at early time points, followed by a sustained release profile controlled by diffusion. MH-b-PS@TMC nanoparticles showed higher cytotoxicity towards MCF-7 cells than free tamoxifen citrate, confirming their effectiveness as a delivery system for administration of lipophilic anticancer drugs.

For the sake of improving patient compliance and sustainability of chemotherapy healthcare system, both TC and CoQ10 were formulated as solid lipid nanoparticles (SLNs). The study was focused on establishing and validating a simple and reproducible spectrophotometric method for simultaneous determination of TC and CoQ10 in their binary mixture or pharmaceutical dosage forms. A new method based on simultaneous estimation of drug mixture without prior separation was developed. Validation parameters were checked with International Conference on Harmonization (ICH) guidelines. The accuracy and reproducibility of proposed method was statistically compared to HPLC. The TC and CoQ10 were quantified at absorptivity wavelengths of 236 nm and 275 nm, respectively. Calibration curves obeyed Beer's law in range of 2–14 µg/ml with a correlation coefficient (R2) of 0.999 in both methanol and simplified simulated intestinal fluid (SSIF). The %means recovery of TC and CoQ10 in pure state or binary mixture at various concentration levels were all around 100%. The low values of SD and %RSD (

Background: In the present investigation, tamoxifen-loaded liposomes transdermal patch was formulated using eudragit-RL, hydroxypropyl methyl cellulose K-50, and ethyl cellulose. Materials and Methods: Liposomes were formulated by solvent evaporation method using poly (sebacic acid-co-ricinoleic acid) in varying ratios and evaluated for particle size, drug loading, entrapment efficiency, transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction. Formulated tamoxifen-loaded liposomes were finally incorporated into transdermal patch and evaluated for thickness drug content, moisture content, moisture uptake, folding endurance, tensile strength diffusion coefficient, permeability coefficient, in vitro permeation, and skin irritation. Optimized transdermal patches were tested for its pharmacokinetic and pharmacodynamics parameters Results: Formulated transdermal patches showed improved bioavailability of tamoxifen when compared to its oral route. Conclusion: Tamoxifen-loaded liposomal transdermal patches could serve as a better alternative to existing marketed formulation in terms of bioavailability.

Primary standard therapy for ER-positive breast cancer being tamoxifen, newer delivery approach for enhancement of dissolution and therapeutic efficiency of tamoxifen through oral route could be a possible solution. In the present study, we investigated combination of tamoxifen (TAM) with resveratrol (RES) and observed that the combination is effective on MCF-7 breast cancer cells. To ensure co-delivery of the drugs, we explored the hot melt extrusion technique for simultaneously extruding two drugs together in order to enhance their bioavailability. As both are class II drugs with dissolution limited bioavailability, detailed formulation and process parameter analyses were carried out. Detailed characterization using microscopy, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD) confirmed that both the drugs were molecularly dispersed in the matrix of Soluplus, CremophorRH40, and Poloxamer188, and no interactions between the ingredients were there during hot melt extrusion (HME) process. Dissolution studies confirmed that HME extrudates were able to release drug more rapidly than simple suspension formulation. Further, pharmacokinetic studies in rats were carried out for tamoxifen. Results demonstrated that extrusion significantly increased the tamoxifen oral bioavailability (p < 0.05) (Tmax = 2.00 ± 0.56 h, Cmax = 3.66 ± 1.49 μg/mL, AUC = 39.80 ± 16.24 μg h/mL, MRT = 20.49 ± 5.71) compared to the conventional suspension of tamoxifen (Tmax = 2.00 ± 0.71 h, Cmax = 2.41 ± 0.84 μg/mL, AUC = 12.82 ± 3.99 μg h/mL, MRT = 18.24 ± 5.95 h). In vitro cytotoxicity studies of TAM, RES, and their combination (TAM-RES) were evaluated with MCF7 cells. The combination showed significantly lower IC50 compared to TAM with increasing ratio of RES which is a result of apoptosis. HME-based simultaneous extrusion of TAM and RES formulation provides a suitable formulation strategy for breast cancer treatment and establishes proof of concept for extruding multiple drugs simultaneously for other applications in future. [ABSTRACT FROM AUTHOR]

Tamoxifen citrate (TXC) is commonly indicated to prevent cell multiplication and development of breast cancer. However, it is usually associated with limited activity and development of toxicity and resistance. This study aimed to describe an in situ pH-responsive niosomes as a carrier for localized and sustained delivery of TXC. The thin film hydration method was utilized to produce TXC niosomes using sorbitan monostearate and cholesterol of 1:1 Molar ratio. The produced formula displayed nano-spherical shape with entrapment efficiency (EE) of 88.90 ± 0.72% and drug release of 49.2 ± 1.51% within 8 h. This formula was incorporated into chitosan/glyceryl monooleate (CH/GMO) as a localized in situ pH-responsive hydrogel delivery system. Different formulae were produced by Design-Expert software based on user-defined response surface design utilizing different chitosan concentration (A) and GMO concentration (B) characterized for mean viscosity (R2) and in vitro release studies (R1). The results displayed that R1 was significantly antagonistic with both of A and B while R2 was significantly synergistic with both of them. The optimum formula was selected and capped with gold as an ideal candidate for computed tomography (CT) to evaluate the efficacy and tissue distribution of TXC utilizing Ehrlich carcinoma mice model. The optimum formula showed localized TXC in a tumour and consequently a significant anti-tumour efficacy compared with free TXC. Based on these outcomes, the novel in situ pH-responsive TXC-loaded noisome could be a promising formula for the efficient treatment of breast cancer. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the potential of chitosan-gellan nanocapsules (CGNCs) for encapsulation and sustained release of Tamoxifen citrate (TMC) for breast cancer therapy. Polyelectrolyte complex coacervation method was used for production of CGNCs. Interaction studies were conducted by Fourier-transform infra-red (FT-IR), differential scanning colorimetric (DSC), and X-ray diffraction (XRD) to investigate any interaction between drug and excipients. Physicochemical parameters, in vitro drug release and release kinetic were studied. In vitro cell viability study using Michigan Cancer Foundation-7 (MCF-7) breast cancer cells was also investigated. CGNCs had a smooth surface and nanosize range with a positive surface charge and exhibited sustained drug release. Further, TMC loaded CGNCs were found to be more cytotoxic than the free drug in MCF-7. Thus CGNCs may be suitable for breast cancer treatment due to delivering the drug at the site of action for a prolonged period of time. [ABSTRACT FROM AUTHOR]

Serious adverse effects and low selectivity to cancer cells are the main obstacles of long term therapy with Tamoxifen (Tmx). This study aimed to develop Tmx-loaded span-based nano-vesicles for delivery to malignant tissues with maximum efficacy. The effect of three variables on vesicle size (Y1), zeta potential (Y2), entrapment efficiency (Y3) and the cumulative percent release after 24 h (Y4) were optimized using Box-Behnken design. The optimized formula was prepared and tested for its stability in different storage conditions. The observed values for the optimized formula were 310.2 nm, − 42.09 mV, 75.45 and 71.70% for Y1, Y2, Y3, and Y4, respectively. The examination using electron microscopy confirmed the formation of rounded vesicles with distinctive bilayer structure. Moreover, the cytotoxic activity of the optimized formula on both breast cancer cells (MCF-7) and normal cells (BHK) showed enhanced selectivity (9.4 folds) on cancerous cells with IC50 values 4.7 ± 1.5 and 44.3 ± 1.3 μg/ml on cancer and normal cells, respectively. While, free Tmx exhibited lower selectivity (2.5 folds) than optimized nano-vesicles on cancer cells with IC50 values of 9.0 ± 1.1 μg/ml and 22.5 ± 5.3 μg/ml on MCF-7 and BHK cells, respectively. The promising prepared vesicular system, with greater efficacy and selectivity, provides a marvelous tool to overcome breast cancer treatment challenges. [ABSTRACT FROM AUTHOR]

A modified coaxial electrospraying process, which was characterized by the use of pure solvent as a sheath working fluid, was developed for the continuous and robust generation of medicated nanoparticles. Tamoxifen citrate (TAM) was encapsulated in zein, a plant protein. The influences of the key parameter shell-to-core fluid flow rate on the electrospraying processes and on the resulting protein-based composite particles were investigated in detail. Scanning electron microscopy images revealed that compared with particles prepared via the traditional single-fluid process, TAM-loaded zein particles prepared via the modified coaxial process were rounder with smaller diameters, narrower smaller size distribution, and more compact inner structures. Owing to the reinforced secondary interactions between TAM and zein, all the particles were similarly amorphous composites, as verified by their X-ray patterns and attenuated total reflectance–Fourier transform infrared spectra. The medicated nanoparticles synthesized via the coaxial process exhibited a better drug sustained-release profile than those synthesized via the traditional single-fluid process, with a smaller initial burst release, longer release period, and shorter tailing-off stage. The microformation mechanisms of the electrosprayed particles and their drug sustained-release mechanisms were suggested. By altering the traditional concept of electrospraying, the modified coaxial electrospraying method developed in this study provides a powerful new process for the generation of nanoparticles with novel structures and functions. [ABSTRACT FROM AUTHOR]

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The aim of this study was to prepare and characterize a new nanocarrier for oral delivery of tamoxifen citrate (TMC) as a lipophilic oral administrated drug. This drug has low oral bioavailability due to its low aqueous solubility. To enhance the solubility of this drug, the microemulsion system was applied in form of oil-in-water. Sesame oil and Tween 80 were used as drug solvent oil and surfactant, respectively. Two different formulations were prepared for this purpose. The first formulation contained edible glycerin as co-surfactant and the second formulation contained Span 80 as a mixed surfactant. The results of characterization showed that the mean droplet size of drug-free samples was in the range of 16.64–64.62 nm with a PDI value of < 0.5. In a period of 6 months after the preparation of samples, no phase sedimentation was observed, which confirmed the high stability of samples. TMC with a mass ratio of 1% was loaded in the selected samples. No significant size enlargement and drug precipitation were observed 6 months after drug loading. In addition, the drug release profile at experimental environments in buffers with pH = 7.4 and 5.5 showed that in the first 24 h, 85.79 and 100% of the drug were released through the first formulation and 76.63 and 66.42% through the second formulation, respectively. The in-vivo results in BALB/c female mice showed that taking microemulsion form of drug caused a significant reduction in the growth rate of cancerous tumor and weight loss of the mice compared to the consumption of commercial drug tablets. The results confirmed that the new formulation of TMC could be useful for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The objective of this revision to examine the properties of panax gensing extract and tamoxifen citrate drug on fertility of male mice testes treated with Doxorubicin, the plant was extracted by using 70%ethanolic alcohol. The mice were divided into five groups: The (T1) was given 300 mg / kg of extract, (T2) was given 150mg/kg of extract and 0.2mg/kg of Tamoxifen, (T3) was given Tamoxifen 0.4 mg/kg, (T4) was given distilled water. Starting from one week, T1,T2 and T3 were intraperitoneally administered 0.15mg/kg of doxorubicin twice weekly for 5 week. (T5) was treated 0.15mg/kg of doxorubicin twice weekly. Results appeared the group given extract display important increase in motility index and turdidimetric analysis of sperms, and decrease in percentage of dead sperm and abnormalitites, the group treated with extract and tamoxifen citrate drug showed important decrease in percentage of dead sperm and abnormalities and important increase in turdidimetric analysis of sperms as compared with tamoxifen group. The histopathological section of testis of doxorubicin group noticed severe degenerative changes in the wall of seminiferous tubules also atrophy in the spermatogonia and Sertoli cells, the section of extract group exhibited increase in number of spermatid and spermatozoa, the section of tamoxifen appeared edema in the interstitial tissue and congestion of blood vessels, the mix of panax gensing extract and tamoxifen citrate displayed decrease in redness of vessels and tissue. From this revision established the extract of panax gensing seeds play important role in increase fertility of male mice by enhance spermatogenesis and have the ability to decrease side effect of tamoxifen citrate.

BACKGROUND AND OBJECTIVE: Ovulation disorders are a common cause of infertility in women. A common cause of anovulation is polycystic ovarian syndrome. Anti-estrogens agents such as clomiphene citrate and tamoxifen citrate are used as first line treatment in polycystic ovary syndrome patients. About 25% of patients may resistant to clomiphene. The aim of this study was to compare the rates of ovulation and pregnancy between tamoxifen citrate and clomiphene citrate in polycystic ovary patients.METHODS: This randomized controlled trial study was performed on 150 polycystic ovary syndrome patients referred to Fatemeh Zahra infertile center and Mehregan hospital in Babol, Iran during 2005 and 2006. Patients randomly divided into two groups and stimulation with clomiphene and tamoxifen on cycle days 2-6 was done. On first cycle, patients were treated with clomiphene (100 mg) and tamoxifen (40 mg) and on the next cycle because of no ovulation or pregnancy patients underwent clomiphene (150mg) and tamoxifen (60mg). Ovulation and pregnancy rates were compared in two groups.FINDINGS: The rate of ovulation in the tamoxifen 40 mg (TMX) group was 41 of 75 (54.7%) and in the clomiphene citrate 100 mg (CC) group was 40 of 75 (53.3%). The rate of ovulation in the TMX group (60mg) was 60 of 73 (82.2%) and in the CC (150mg) was 44 of 70 (62.9%) (p=0.014). There were 5 pregnancies in the TMX group (6.7%) and 10 pregnancies in the CC group (13.3%) that there was not significant difference between two groups.CONCLUSION: According to the results of this study, for increasing ovulation rate and pregnancy in polycystic ovary syndrome patients who were resistant to clomiphene, tamoxifen can be used.