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Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), glycerol-developed vesicles, as innovative nanovesicles for successful ITZ pulmonary drug delivery. Methods: The glycerosomes were functionalized with hyaluronic acid (HA-GLY) to potentiate the anticancer efficacy of ITZ and extend its local bio-fate. ITZ-HA-GLY were fabricated using soybean phosphatidylcholine, tween 80, HA, and sonication time via a thin-film hydration approach according to a 24 full factorial design. The impact of formulation parameters on ITZ-HA-GLY physicochemical properties, as well as the optimal formulation option, was evaluated using Design-Expert®. Sulphorhodamine-B (SRB) colorimetric cytotoxicity assay of the optimized ITZ-HA-GLY versus ITZ suspension was explored in the human A549 cell line. The in vivo pharmacokinetics and bio-distribution examined subsequent to intratracheal administrations of ITZ suspension, and ITZ-HA-GLY were scrutinized in rats. Results: The optimized ITZ-HA-GLY unveiled vesicles of size 210.23 ± 6.43 nm, zeta potential of 41.06 ± 2.62 mV, and entrapment efficiency of 73.65 ± 1.76%. Additionally, ITZ-HA-GLY manifested a far lower IC50 of 13.03 ± 0.2 µg/mL on the A549 cell line than that of ITZ suspension (28.14 ± 1.6 µg/mL). Additionally, the biodistribution analysis revealed a higher concentration of ITZ-HA-GLY within the lung tissues by 3.64-fold as compared to ITZ suspension. Furthermore, the mean resistance time of ITZ-HA-GLY declined more slowly with 14 h as compared to ITZ suspension, confirming the accumulation of ITZ inside the lungs and their promising usage as a target for the treatment of lung disease. Conclusions: These data indicate that the improved ITZ-HA-GLY demonstrates significant promise and represents an exciting prospect in intratracheal delivery systems for lung cancer treatment, meriting further investigation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Raloxifene (RLF) is a therapeutic option for invasive breast cancer because it blocks estrogen receptors selectively. Low solubility, limited targeting, first-pass action, and poor absorption are some of the challenges that make RLF in oral form less effective. This study aimed to create an intra-tumoral in situ pH-responsive formulation of RLF–invasome (IPHRLI) for breast cancer treatment, with the goals of sustaining RLF release, minimizing adverse effects, and enhancing solubility, bioavailability, targeting, and effectiveness. Methods: Numerous RLF–invasome formulations were optimized using design expert software (version 12.0.6.0, StatEase Inc., Minneapolis, MN, USA). Integrating an optimal formulation with an amalgam of chitosan and glyceryl monooleate resulted in the IPHRLI formulation. In vivo testing of the IPHRLI formulation was conducted utilizing the Ehrlich cancer model. Results: Requirements for an optimum RLF–invasome formulation were met by a mixture of phospholipids (2.46%), ethanol (2.84%), and cineole (0.5%). The IPHRLI formulation substantially sustained its release by 75.41% after 8 h relative to free RLF. The bioavailability of intra-tumoral IPHRLI was substantially raised by 4.07-fold compared to oral free RLF. Histopathological and tumor volume analyses of intra-tumoral IPHRLI confirmed its efficacy and targeting effect. Conclusions: the intra-tumoral administration of the IPHRLI formulation may provide a potential strategy for breast cancer management. [ABSTRACT FROM AUTHOR]