Quality-by-Design Optimization of Biotin-Coated Tetronic® 1107 Polymersomes for Carboplatin Delivery in Non-Small Cell Lung Cancer

Background: For driver-negative Non-Small Cell Lung Cancer (NSCLC), platinum-based chemotherapy remains standard; however, carboplatin efficacy is limited by poor tumour delivery and dose-limiting toxicity. In this study, we developed biotin-functionalised polymersomes encapsulating carboplatin to enhance carrier stability and enable selective tumour delivery via sodium-dependent multivitamin transporter uptake. Materials and Methods: A Box-Behnken design optimised Tetronic® 1107 polymersomes by modelling polymer concentration, temperature, and stirring time against particle size, zeta potential, and entrapment efficiency. The optimised formulation was characterised by dynamic light scattering (particle size distribution); atomic force and scanning electron microscopy (morphology); Fourier-transform infrared spectroscopy (interactions); differential scanning calorimetry (thermal behaviour); and powder X-ray diffraction (crystallinity). It was further evaluated for pH-dependent release and cytotoxicity in biotin-overexpressing A549 cells. Results: Box-Behnken optimisation yielded SMVT-targeted, biotin-functionalised Tetronic® 1107 polymersomes (PS = 246 nm; ZP = –26 mV; EE = 85%). FTIR, DSC, and XRD showed a preserved PEO/PPO matrix with amorphous carboplatin. AFM and SEM revealed a corrugated, biotin-rich corona. Release was sustained and pH-responsive, fitting the Weibull model (R²=0.93-0.97). In A549 cells, biotin-coated vesicles reduced the IC₅₀ 1.73-fold relative to free carboplatin (p < 0.05). Conclusion: Biotin-functionalised polymersomes improved carboplatin loading, stability, and tumour-targeted cytotoxicity, supporting their evaluation in vivo for NSCLC therapy.