# Improved Anticancer Activity of the Malloapelta B-Nanoliposomal Complex against Lung Carcinoma
## 4 Discussion  
In addition to novel treatments for cancer, such as antibodies and gene therapy, a number of drugs based on natural bioactive compounds have been shown to be efficacious in chemotherapy and the prevention of cancer. Therefore, there is much interest in identifying potential new anticancer compounds, such as the large-scale programs of the National Cancer Institute for the discovery and screening of natural products for development as anticancer drugs [11]. These studies have identified a number of categories of novel compounds with anticancer activities. However, the use of these compounds has been hampered by their toxicity and poor solubility, problems that have also prevented the development of malB for clinical use. Previous reports regarding its promising anticancer activities suggested that malB was a promising candidate for drug development. Microarray analysis demonstrated that this compound has anticancer capacity in vitro by regulating gene expression similar to the commercial anticancer drug, withanolide A [12]. This compound was also shown to inhibit the activation of NF-kB with an IC\({}_{50}\) value in the range of 3.5-5.0 uM [3,5]. The compound affected NF-kB activation by inhibiting the activation of IxkB kinase (IKK) [6]. However, malB shows high toxicity and is insoluble, which has limited its pharmaceutical applications. The use of nanoliposomal carriers for drug design to reduce toxicity and enhance the bioavailability of natural compounds is appropriate for anticancer drug development. Drugs packed into liposomes show improved blood circulation activity, promotion of deposition in tumors, protection from metabolism, direct distribution of the drug into tumors, as well as enhanced uptake in adenocarcinoma, mononuclear macrophages, and the intracellular lattice system (liver, spleen, bone marrow). Furthermore, liposomal-encapsulated drugs show reduced uptake in the kidneys, myocardium, and brain tissues [13,14]. In the present study, malB was experimentally incorporated into liposomal nanocarriers. The nanoliposomes containing malB were small unilamellar vesicles \(<\)200 nm in diameter with a slight negative charge and low PDI. [PERSON] reported that nanoliposomes in the size range of 50-200 nm would be the most suitable for liposomal stability in the body [15, 16, 17]. However, liposomes containing cholesterol had much lower EE in comparison with the non-cholesterol formulations. Similar results were reported previously for some lipophilic drugs, such as ciprofloxacin [18] and dexamethasone [19], as well as natural compounds, such as ascorbic acid [20]. Cholesterol molecules are normally located in the space between lipid bilayer membranes. Therefore, it was supposed that cholesterol competed out malB molecules and some positions in the bilayers were occupied, preventing successful incorporation of the test compound. Furthermore, cholesterol makes the bilayer more rigid, which would make the incorporation of malB molecules difficult. In this study, the addition of \begin{table}
\begin{tabular}{c c c} \hline
**Groups** & **Mean Survival Time (Days)** & **\% ILS** \\ \hline Control group (normal saline) & 30.20 \(\pm\) 0.86 & - \\ \hline Blank nanoliposome & 30.67 \(\pm\) 0.80 & 1.56 \\ malB free (5 mg/kg b.w.) & 31.00 \(\pm\) 0.84 & 2.65 \\ malB-nanoliposomes (2.5 mg/kg b.w.) & 31.20 \(\pm\) 0.86 & 3.31 \\ malB-nanoliposomes (5 mg/kg b.w.) & 32.20 \(\pm\) 0.97 & 6.62 \\ Doxorubicin (5 mg/kg b.w.) & 36.20 \({}^{*}\)\(\pm\) 0.86 & 19.86 \\ \hline \end{tabular} \({}^{*}\)\(p<0.05\) in comparison with the control group (normal saline treated).  
\end{table} 
Table 4: Effect of malB-nanoliposome and free malB on survival time of LLC-induced tumor-bearing mice from different experimented groups (mean \(\pm\) SEM) (\(n=6\)). cholesterol caused a noticeable decrease in EE, which was taken to indicate that EE depends on the normal structure of the liposomal bilayer [21].