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Aim & Objective: This study evaluates the potential of combining paclitaxel (PTX) and bortezomib (BTZ) for breast cancer therapy. Materials & Methods: The nanoformulation was optimized via Box-Behnken Design (BBD), with method validation adhering to US-FDA guidelines. Results: Multiple reaction monitoring transitions for PTX, BTZ and internal standard were m/z 855.80→286.60, 366.80→226.00 and 179.80→110.00, respectively. Elution done on C18 Luna column with 0.1% FA in MeOH:10 mM ammonium acetate. The size of nanoformulation was 133.9 ± 1.97 nm, PDI 0.19 ± 0.01 and zeta potential -19.20 ± 1.36 mV. Pharmacokinetics showed higher Cmax for PTX-BTZ-NE (313.75 ± 10.71 ng/ml PTX, 11.92 ± 0.53 ng/ml BTZ) versus free PTX-BTZ (104 ± 13.06 ng/ml PTX, 1.9 ± 0.08 ng/ml BTZ). Conclusion: Future findings will contribute to the treatment of breast cancer using PTX and BTZ. Graphical Abstract Article highlights The importance of paclitaxel (PTX) and bortezomib (BTZ) in combination with chemotherapy is demonstrated by recently published studies. An obstacle to measuring the results of translational research is the lack of an analytical or bioanalytical approach for simultaneously estimating PTX and BTZ. A gap in the scientific literature has been filled by the development and validation of an LC-MS/MS method for the co-estimation or simultaneous measurement of PTX and BTZ. Both moieties were resolved in a Phenomenex Luna (C18), (7.5 × 4.6 mm, 3μ) column with a 0.1% FA in MeOH:10 mM ammonium acetate, 80:20 (% v/v) mobile phase at 0.6 ml/min flow rate. According to the US-FDA, the developed method was validated in female Sprague–Dawley rats plasma for different characteristics, such as linearity, precision and accuracy, LLOQ and stability studies. The oral P.K profile of PTX and BTZ co-loaded in a nanoformulation has been investigated in young female Sprague–Dawley rats to support the applicability of the established LC-MS/MS methodology. With an LLOQ of 1.0 ng/ml for each drug and a run time of 6.0 min, the calibration curve was found linear for the 1–600 ng/ml concentration range. The proposed LC-MS/MS method was confirmed to be repeatable, precise and accurate. The developed LC-MS/MS method was successfully illustrated for the co-estimation or simultaneous estimation of both drugs in rat plasma to generate an oral P.K profile. US-FDA Guidance of Industry and Bioanalytical Method Validation criteria was followed for the co-estimation of PTX and BTZ and was applied to nanoformulation development and bioanalytical investigations. [ABSTRACT FROM AUTHOR]

Background: The present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-α-tocopheryl-polyethylene glycol succinate (TPP-TPGS1000) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. Materials & methods: A quality-by-design approach was applied for optimization and in vitro and in vivo characterization were performed. Results: The TPP-TPGS1000-PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and G2M cell cycle arrest compared with free-PTX treatment. In addition, pharmacokinetics, biodistribution and in vivo live imaging studies in tumor-bearing mice showed that TPP-TPGS1000-PTX-NE had superior performance compared with free-PTX treatment. Histological and survival investigations ascertained the nontoxicity of the nanoformulation, suggesting new opportunities and potential to treat breast cancer. Conclusion: TPP-TPGS1000-PTX-NE improved the efficacy of breast cancer treatment by enhancing its effectiveness and decreasing drug toxicity. [ABSTRACT FROM AUTHOR]

Though paclitaxel (PTX) and doxorubicin (DOX) are amongst the most widely used and investigated drug pair for combination chemotherapy but surprisingly, not a single validated HPLC-UV method is available to analyze PTX and DOX simultaneously. So, herein a HPLC-UV method is developed and validated for the same, filling an indispensable gap in the literature. As these two moieties have characteristically different polarities, resolving them under the common chromatographic conditions is a challenging task. Herein, the principle of ion pair chromatography is utilized to resolve these two moieties on a C18 column employing an isocratic mobile phase comprised of acetonitrile and octane sulfonic acid buffer (67 : 37) and detected simultaneously at 231 nm using a UV detector only. The retention time is 4.4 and 7.2 min for PTX and DOX, respectively, with a total analysis time of less than 10 minutes, suitable for the formulation development and research, while LOQ is less than 0.066 μg/ml for both the drugs, suitable for the therapeutic drug monitoring at preclinical and clinical research setup. To substantiate the applicability of the developed method, a nanoformulation coloaded with PTX and DOX was designed and analyzed using the developed protocol. The method is also applied successfully to study the plasma kinetic profile of both the moieties simultaneously in Balb/c mice. Further, the method is validated as per the ICH guidelines fulfilling the unmet need of a validated analytical tool to simultaneously estimate PTX and DOX. Moreover, the results suggest that the principal of common ion chromatography demonstrated here can also be applied further for the simultaneous chromatographic separation of other polar and nonpolar moieties too. Consequently, the reported method surely will advance the toolset required for the precision-based combination chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-α-tocopheryl-polyethylene glycol succinate (TPP-TPGS 1000 ) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. Materials & methods: A quality-by-design approach was applied for optimization and in vitro and in vivo characterization were performed. Results: The TPP-TPGS 1000 -PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and G 2 M cell cycle arrest compared with free-PTX treatment. In addition, pharmacokinetics, biodistribution and  in vivo live imaging studies in tumor-bearing mice showed that TPP-TPGS 1000 -PTX-NE had superior performance compared with free-PTX treatment. Histological and survival investigations ascertained the nontoxicity of the nanoformulation, suggesting new opportunities and potential to treat breast cancer. Conclusion: TPP-TPGS 1000 -PTX-NE improved the efficacy of breast cancer treatment by enhancing its effectiveness and decreasing drug toxicity.