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<p>Parkinson's disease (PD) causes dopaminergic neuron loss and metabolic and epigenetic abnormalities. DNMT inhibitor decitabine (DB) promotes neuroprotective genes repressed by methylation. Repaglinide (RP), an insulin secretagogue used in T2DM, a PD comorbidity, reduces oxidative stress and inflammation by improving insulin signaling and regulating SIRT1 and HDACs. Bioavailability and half-life are issues for both drugs. Our innovative RP-HPLC technology and solid lipid nanoparticle (SLN) system for dual-drug administration enable prolonged release, brain targeting, and better pharmacokinetics for effective PD treatment. DB and RP were separated using a Waters™ e2695 HPLC system with a PDA detector and a Phenomenex Luna PFP column (250 × 4.6&#xa0;mm, 5&#xa0;µm) for enhanced selectivity. A 40:60 isocratic mobile phase (Solvent A:B) was optimized for peak shape and resolution. DB and RP were eluted at 2.7 and 3.6&#xa0;min, respectively, throughout a 6-min run. The approach enabled precise, consistent, contemporaneous detection of both analytes for high-throughput analysis. Following conventional recommendations, the technique was validated for appropriateness, specificity, linearity, precision, accuracy, and robustness. The validated approach determined 53.26% and 76.68% drug entrapment efficiency in DB and RP SLN formulations. The MTT assay showed that DB and RP preserved N2A cell viability, signifying neuroprotective effects. The results confirmed the method's reliability, making it suitable for other applications, such as the simultaneous detection and quantification of these drugs in liposomal systems, polymer–lipid hybrid nanoparticles, and lipid–drug conjugates for in vitro and in vivo release and entrapment studies.</p>

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Development and Validation of RP-HPLC Method for Simultaneous Determination of Decitabine and Repaglinide: Application to Solid Lipid Nanoparticle Formulations with In Vitro Neurotoxicity Assessment

  • 期刊论文

  • 发表日期：

    2025年11月16日

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  • Shobha Kumari,
  • Shiva Kumar Gogikar,
  • Amol G. Dikundwar,
  • Sunil Kumar Dubey,
  • Rajeev Taliyan

摘要

Parkinson's disease (PD) causes dopaminergic neuron loss and metabolic and epigenetic abnormalities. DNMT inhibitor decitabine (DB) promotes neuroprotective genes repressed by methylation. Repaglinide (RP), an insulin secretagogue used in T2DM, a PD comorbidity, reduces oxidative stress and inflammation by improving insulin signaling and regulating SIRT1 and HDACs. Bioavailability and half-life are issues for both drugs. Our innovative RP-HPLC technology and solid lipid nanoparticle (SLN) system for dual-drug administration enable prolonged release, brain targeting, and better pharmacokinetics for effective PD treatment. DB and RP were separated using a Waters™ e2695 HPLC system with a PDA detector and a Phenomenex Luna PFP column (250 × 4.6 mm, 5 µm) for enhanced selectivity. A 40:60 isocratic mobile phase (Solvent A:B) was optimized for peak shape and resolution. DB and RP were eluted at 2.7 and 3.6 min, respectively, throughout a 6-min run. The approach enabled precise, consistent, contemporaneous detection of both analytes for high-throughput analysis. Following conventional recommendations, the technique was validated for appropriateness, specificity, linearity, precision, accuracy, and robustness. The validated approach determined 53.26% and 76.68% drug entrapment efficiency in DB and RP SLN formulations. The MTT assay showed that DB and RP preserved N2A cell viability, signifying neuroprotective effects. The results confirmed the method's reliability, making it suitable for other applications, such as the simultaneous detection and quantification of these drugs in liposomal systems, polymer–lipid hybrid nanoparticles, and lipid–drug conjugates for in vitro and in vivo release and entrapment studies.