Preparation, characterization, and in vitro evaluation of bleomycin‐containing nanoliposomes

Abstract

Bleomycin is an anticancer drug used against various types of cancers. The aim of this study was to prepare a new PEGylated and non-PEGylated nanoliposomal formulation of bleomycin (PEG-nLip-BLM and nLip-BLM) and evaluate their anticancer activity in different tumor cell lines. The liposomes were prepared by thin-film hydration method, and then, bleomycin (BLM) was loaded to the prepared vesicles. The size, zeta potential, entrapment efficiency, loading rate, release profile, and cytotoxicity of liposomal formulations in TC-1, LLC1, and HFLF-PI5 cell lines were investigated. Mean particle size and zeta potential of the PEG-nLip-BLM and nLip-BLM were found to be 99.4 ± 4.6 nm and -34.83 ± 4.7 mV; and 112.2 ± 7.2 nm and -27.5 ± 3.2 mV, respectively, which were stable for at least 2 months. Encapsulation and loading efficiency of BLM for PEG-nLip-BLM and nLip-BLM were obtained about 83.1 ± 4.2% and 14.3 ± 2.5%; and 78.3 ± 8.6% and 11.1 ± 3.3%, respectively. Drug release study showed a slow release pattern without considerable burst effect. The liposomal formulations indicated lower toxicity compared to free drug in case of TC-1 and HFLF-PI5 cells, but their cytotoxicity against LLC1 cells was significantly higher than free drug. The results of this study indicated that PEG-nLip-BLM can be a suitable candidate for drug delivery to solid tumors.

Development and Characterization of Nanoliposomal Hydroxyurea Against BT-474 Breast Cancer Cells

“…29 Zeta potential is a significant criterion in the stability of liposome formulations and in blocking their aggregation, as well. 30 Zeta potential of nanoliposomes was negative because of the existence of carboxylic groups of lipids, drug-to-lipid ratio, pH, and type of lipids used in the liposomes. The obtained zeta potential was enough to keep the stability of liposomal formulations.…”

“…31 The EE% of HU was high because of the suitable HU-loading method and drug to lipid ratio. 30,32 Profile, kinetic, and mechanism of drug release The pattern of drug release for free HU and NL-HU at pH = 7.4 was presented in Figure 3. Within ten h of drug release at 37°C in the buffer, 67 ± 4.2% of free HU and 11 ± 0.41% of NL-HU were released, respectively.…”

Enhanced antitumor effect of targeted nanoliposomal bleomycin

“…The morphological properties of liposomes were examined using a scanning electron microscopy. Entrapment and loading efficiencies of BLM in liposomes were measured by HPLC according to European pharmacopoeia 2005 method as described before . The physiochemical stability of the nanoliposomes was evaluated by measurement of particle size, polydispersity index (PDI), zeta potential, entrapment, and loading efficiencies immediately after production and during 2 months storage at 4–8°C.…”

“…Moreover, its clinical application is restricted by dose‐related development of side‐effects . To decrease the side‐effects and increase the therapeutic efficacy of BLM, in recent years, different formulations of BLM have been developed, and in some cases, promising results have been obtained . Alexander and his colleagues developed an octaarginine (R8)‐modified fusogenic DOPE‐liposomes of BLM (R8‐DOPE‐BLM).…”

“…[2,5] To decrease the side-effects and increase the therapeutic efficacy of BLM, in recent years, different formulations of BLM have been developed, and in some cases, promising results have been obtained. [6][7][8] Alexander and his colleagues developed an octaarginine (R8)-modified fusogenic DOPE-liposomes of BLM (R8-DOPE-BLM). This formulation led to significantly stronger cell death and DNA damage in vitro compared to all controls and showed a potent antitumor effect in mice bearing breast cancer 4T1 tumors.…”