Abstract
Gemcitabine (Gem) and cisplatin (Cis) are currently being used for lung cancer treatment, but they are highly toxic in high dosages. This research aimed to develop a niosome formulation containing a low-dosage Gem and Cis (NGC), as an alternative formulation for lung cancer treatment. NGC was prepared using a very simple heating method and was further optimized by D-optimal mixture design. The optimum NGC formulation with particle size, polydispersity index (PDI), and zeta potential of 166.45 nm, 0.16, and −15.28 mV, respectively, was obtained and remained stable at 27 °C with no phase separation for up to 90 days. The aerosol output was 96.22%, which indicates its suitability as aerosolized formulation. An in vitro drug release study using the dialysis bag diffusion technique showed controlled release for both drugs up to 24 h penetration. A cytotoxicity study against normal lung (MRC5) and lung cancer (A549) cell lines was investigated. The results showed that the optimized NGC had reduced cytotoxicity effects against both MRC5 and A549 when compared with the control (Gem + Cis alone) from very toxic (IC50 < 1.56 µg/mL) to weakly toxic (IC50 280.00 µg/mL) and moderately toxic (IC50 = 46.00 µg/mL), respectively, after 72 h of treatment. These findings revealed that the optimized NGC has excellent potential and is a promising prospect in aerosolized delivery systems to treat lung cancer that warrants further investigation.
Highlights
Over the past fifty years, major public health concern for cancer diseases has been rising, especially for lung cancer, which is the most common cancer diagnosed in the world, contributing to 37% of the leading causes of cancer-related death worldwide from total deaths in 2018 [1]
The study of drug solubility plays an important role in determining the maximum amount of drugs, Gem and Cis, that can dissolve in 0.90% w/v NaCl solution, which acts as an aqueous medium in NGC formulation
The results of this study demonstrated that the optimized NGC formulation was successfully formulated using a heating method with good stability and homogeneity against phase separation at different temperatures during 90 days of storage
Summary
Over the past fifty years, major public health concern for cancer diseases has been rising, especially for lung cancer, which is the most common cancer diagnosed in the world, contributing to 37% of the leading causes of cancer-related death worldwide from total deaths in 2018 [1]. A significant factor that leads to lung cancer is cigarette smoking. Increasing lung cancer cases among non-smokers are quite alarming nowadays [3]. Different stages of lung cancer with different treatments are the primary reason for the low survival rate of cancer patients. In other cancer cases, detection and confirmation usually can only be made at stage four (IV) [4]. The current treatments used for lung cancer are surgery, chemotherapy, and radiation therapy depending on the stage and overall performance of cancer cells. For the advanced stage of lung cancer, chemotherapy
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