Aim: This study aimed to formulate erlotinib hydrochloride (ERT-HCL)-loaded chitosan (CS) and poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using Quality-by-Design (QbD) to optimize critical quality attributes (CQAs). Materials & methods: Quality target product profile (QTPP) and CQAs were initially established. Based on L8-Taguchi screening and risk assessments, central composite design (CCD) design was used to optimize NPs. Results: ERT-HCL-loaded CS-PLGA NPs had a mean particle diameter, zeta potential and entrapment efficiency of 226.50 ± 1.62 d.nm, 27.66 ± 0.64 mV and 78.93 ± 1.94 %w/w, respectively. The NPs exhibited homogenous spherical morphology and sustained release for 72 h. Conclusion: Using systematic QbD approach, ERT-HCL was encapsulated in CS-PLGA NPs, optimizing CQAs. These findings propel future research for improved NSCLC treatment.

Glaucoma causes irreversible blindness, with poor adherence driven by frequent dosing and low eye drop bioavailability. Brimonidine tartrate (BRT) requires multiple daily doses due to rapid elimination and limited corneal permeability. To address these limitations, this study aimed to develop a long-acting, mucoadhesive ocular delivery system using hyaluronic acid-coated cubosomes (HA-BRT-CUB), further incorporated into a thermoresponsive in situ gel (HA-BRT-CUB-ISG). The HA-BRT-CUB formulation was optimized using a Design of Experiments (DoE) approach, resulting in a particle size of 189.24 ± 2.05 nm, zeta potential of -25.45 ± 0.88 mV, and entrapment efficiency of 78.86 ± 2.42%. Incorporation into a poloxamer-based ISG system enhanced precorneal retention and sustained delivery. In vitro release from HA-BRT-CUB-ISG was extended over 24 h (h), best fitting the Korsmeyer-Peppas model (R² = 0.981). Ex vivo permeation studies revealed a flux (J) of 2.89 µg/cm²/h and a 3.92-fold enhancement ratio (ER) compared to the BRT solution. In normotensive New Zealand rabbits, HA-BRT-CUB-ISG achieved a 30.31% IOP reduction at 24 h (17.05 ± 0.35 mmHg), compared to 29.91% with HA-BRT-CUB and only 20.75% with Alphagan^®. Pharmacokinetic analysis revealed that HA-BRT-CUB-ISG attained a Cmax of 7.35 ± 0.82 μg/mL and an AUC₀-∞ of 70.22 ± 3.56 µg/mL* h, representing a 4.5- and 12-fold improvement, respectively, over Alphagan^®. The half-life extended to 8.75 ± 1.34 h with minimal clearance (Cl/F = 1.42 ± 0.59). Stability studies confirmed HA-BRT-CUB formulation integrity under refrigerated conditions over 90 days. Overall, HA-BRT-CUB-ISG presents a promising once-daily nanocarrier system for sustained glaucoma management.