Background/objectives: Idiopathic pulmonary fibrosis (IPF) is a prevalent interstitial lung disease that typically progresses gradually, leading to respiratory failure and ultimately death. IPF can be treated with the tyrosine kinase inhibitor, nintedanib (NTD), owing to its anti-fibrotic properties, which ameliorate the impairment of lung function. This study aimed to formulate, optimize, and assess NTD-loaded ufasomes (NTD-UFSs) as a nanosystem for its pulmonary targeting to snowball the bioavailability and therapeutic efficacy of the drug. Methods: To investigate the influence of numerous factors on NTD-UFSs assembly and to determine the optimal formulation, Box–Behnken statistical design was implemented with the assistance of Design-Expert^® software. The thin-film hydration strategy was employed to fabricate NTD-UFSs. The optimum NTD-UFSs formulation was subsequently selected and subjected to additional evaluations. Also, using a rat model, a comparative pharmacokinetic analysis was scrutinized. Results: The optimal NTD-UFSs elicited an accumulative release of 65.57% after 24 h, an encapsulation efficiency of 62.51%, a zeta potential of −36.07 mV, and a vesicular size of 364.62 nm. In addition, it disclosed remarkable stability and a continuous cumulative release pattern. In vivo histopathological studies ascertained the tolerability of NTD-UFSs administered intratracheally. According to the pharmacokinetic studies, intratracheal NTD-UFSs administration manifested a significantly higher AUC_0–∞ value than oral and intratracheal NTD suspensions, by approximately 5.66- and 3.53-fold, respectively. Conclusions: The findings of this study proposed that UFSs might be a promising nanoparadigm for the non-invasive pulmonary delivery of NTD.

Background/Objectives: Nintedanib (NTD), a triple tyrosine kinase receptor inhibitor, is the recommended first-line tackling option for idiopathic pulmonary fibrosis (IPF). Nevertheless, the adequacy of NTD is curtailed by issues associated with its low solubility, first-pass effect, poor bioavailability, and liver toxicity. The objective of our work was to develop a non-invasive intratracheal (i.t.) nanoparadigm based on NTD-loaded polymeric mixed micelles (NTD-PMMs) that can effectively treat IPF by sustaining the release of NTD, and snowballing its bioavailability, solubility, and efficacy. Methods: Design-Expert^® software was used to optimize various NTD-PMMs formulations via Box–Behnken design adopting the thin-film hydration technique. The optimum formulation was chosen and in vivo tested in a rat model to explore its comparative bioavailability and toxicity. Results: The formulation composition with 309.217 mg of Soluplus, 150 mg of Tween 80, and 40 mg of sodium deoxycholate was found to fulfill the requisites of an optimum NTD-PMMs formulation. The optimum NTD-PMMs formulation divulged 90.26% entrapment efficiency with a surface charge of −14.72 mV and a nanoscale diameter of 61.36 nm. Also, it substantially sustained the release of NTD by 66.84% after 24 h and manifested a pronounced stability. In vivo histopathology investigations verified the safety of NTD-PMMs delivered intratracheally. Moreover, pharmacokinetic analyses disclosed accentuated relative bioavailability of the optimized NTD-PMMs by 2.4- and 3.82-fold as compared with both the i.t. and oral crude NTD suspensions, respectively. Conclusions: Overall, the current results elicited the potential of PMMs to serve as a promising pulmonary nanovector for the targeted delivery of NTD.

Background/Objectives: Basal cell skin cancer (BCSC) develops when skin cells proliferate uncontrollably. Sonidegib (SDB) is a therapeutic option for the treatment of BCSC by inhibiting hedgehog signaling. The problems with SDB’s low solubility, poor bioavailability, resistance, poor targeting, and first-pass action make it less effective when taken orally. This investigation set out to design an intratumoral in situ pH-sensitive hydrogel of SDB-invasomes (IPHS-INV) that can effectively treat BCSC by improving SDB’s bioavailability, sustainability, targeting, and efficacy while also reducing its resistance and undesirable side effects. Methods: Numerous S-INV formulations were developed using Box–Behnken Design Expert and tested before settling on the optimum S-INV formulation. An experimental 7, 12-dimethylbenzanthracene (DMBA) carcinoma rat model was used for in vivo studies of the IPHS-INV formulation after it was combined with chitosan. Results: Phospholipids (1.72% w/w), cholesterol (0.15% w/w), ethanol (1% v/v), and cineole (1.5% v/v) were shown to be the optimal components in the SDB-invasome formulation. The IPHS-INV formulation outperformed the permeation and bioavailability of free SDB by 7.14 and 6 times, respectively, and sustained its release by 57.41%. The IPHS-INV formulation showed a decrease in tumor volume of 99.05% and a reduction of hypercellular tumors, indicating its anti-cancer activity. The intratumoral IPHS-INV formulation maintained a higher concentration of SDB in tumors, indicating its targeting activity. Conclusions: These findings support the use of the intratumoral IPHS-INV formulation as an effective strategy for the treatment of BCSC.