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Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted. The selected nanoemulsion formulations were prepared using high-energy emulsification technique and subjected to physicochemical and aerodynamic characterizations. The formulated nanoemulsion had mean particle size and ζ-potential in the range of 90 to 110 nm and − 30 to − 40 mV respectively, indicating high colloidal stability. The pH, osmolality, and viscosity of the systems met the ideal requirement for pulmonary application. The DNE4 formulation exhibited slow drug release and excellent stability even under the influence of extreme environmental conditions. This was further confirmed by transmission electron microscopy as uniform spherical droplets in nanometer range were observed after storage at 45 ± 1 °C for 3 months indicating high thermal stability. The nebulized DNE4 exhibited desirable aerosolization properties for pulmonary delivery application and found to be more selective on human lung carcinoma cell (A549) than normal cell (MRC-5). Hence, these characteristics make the formulation a great candidate for the potential use as a carrier system for docetaxel in targeting lung cancer via pulmonary delivery. [ABSTRACT FROM AUTHOR]

Inhalation therapy of lipid-based carriers has great potential in direct target towards the root of respiratory diseases, which make them superior over other drug deliveries. With the successful entry of lipid carriers into the target cells, drugs can be absorbed in a sustained release manner and yield extended medicinal effects. Nevertheless, translation of inhalation therapy from laboratory to clinic especially in drug delivery remains a key challenge to the formulators. An ideal drug vehicle should safeguard the drugs from any premature elimination, facilitate cellular uptake, and promote maximum drug absorption with negligible toxicity. Despite knowing that lung treatment can be done via systemic delivery, pulmonary administration is capable of enhancing drug retention within the lungs, while minimizing systemic toxicity with local targeting. Current inhalation therapy of lipid-based carriers can be administered either intratracheally or intranasally to reach deep lung. However, the complex dimensions of lung architectural and natural defense mechanism poise major barriers towards targeted pulmonary delivery. Delivery systems have to be engineered in a way to tackle various diseases according to their biological conditions. This review highlights on the developmental considerations of lipid-based delivery systems cater for the pulmonary intervention of different lung illnesses. [ABSTRACT FROM AUTHOR]

Conventional chemotherapy often results in toxicity to normal cells and hampers cancer treatment efficacy. Cancer targeting via surface-functionalized nanocarrier offers an excellent opportunity for tackling this unwanted issue. However, a comprehensive understanding of its toxicity and safety in biological entities remains limited. In this study, we report the cancer-selectivity of surface-functionalized nano-zeolitic imidazolate framework-8 (FA@nZIF-8) and its safety characteristics in small organisms including zebrafish embryos and brine shrimp. The FA@nZIF-8 exhibited higher selectivity (3.95) towards cancer cells (MCF7) compared to pure nZIF-8. Moreover, this functionalized nano-ZIF-8 not only enhanced permeability performance but also appeared to be a significant survivability advantage, 80% (P < 0.001) with a higher survival rate compared with pure nZIF-8 at the 96-h mark. No scoliosis appeared in healthy zebrafish embryos for both nanoparticle systems. Monitoring brine shrimps showed minimal toxicity induction at a certain level of concentration. This study suggests that surface-functionalized FA@nZIF-8, with its cancer-selective behavior and promising safety characteristics, has bright potential for further exploration in cancer therapy.Graphical Abstract: Conventional chemotherapy often results in toxicity to normal cells and hampers cancer treatment efficacy. Cancer targeting via surface-functionalized nanocarrier offers an excellent opportunity for tackling this unwanted issue. However, a comprehensive understanding of its toxicity and safety in biological entities remains limited. In this study, we report the cancer-selectivity of surface-functionalized nano-zeolitic imidazolate framework-8 (FA@nZIF-8) and its safety characteristics in small organisms including zebrafish embryos and brine shrimp. The FA@nZIF-8 exhibited higher selectivity (3.95) towards cancer cells (MCF7) compared to pure nZIF-8. Moreover, this functionalized nano-ZIF-8 not only enhanced permeability performance but also appeared to be a significant survivability advantage, 80% (P < 0.001) with a higher survival rate compared with pure nZIF-8 at the 96-h mark. No scoliosis appeared in healthy zebrafish embryos for both nanoparticle systems. Monitoring brine shrimps showed minimal toxicity induction at a certain level of concentration. This study suggests that surface-functionalized FA@nZIF-8, with its cancer-selective behavior and promising safety characteristics, has bright potential for further exploration in cancer therapy. [ABSTRACT FROM AUTHOR]