Enhanced localization of anticancer drug in tumor tissue using polyethylenimine-conjugated cationic liposomes

Abstract

Liposome-based drug delivery systems hold great potential for cancer therapy. However, to enhance the localization of payloads, an efficient method of systemic delivery of liposomes to tumor tissues is required. In this study, we developed cationic liposomes composed of polyethylenimine (PEI)-conjugated distearoylglycerophosphoethanolamine (DSPE) as an enhanced local drug delivery system. The particle size of DSPE-PEI liposomes was 130 ± 10 nm and the zeta potential of liposomes was increased from -25 to 30 mV by the incorporation of cationic PEI onto the liposomal membrane. Intracellular uptake of DSPE-PEI liposomes by tumor cells was 14-fold higher than that of DSPE liposomes. After intratumoral injection of liposomes into tumor-bearing mice, DSPE-PEI liposomes showed higher and sustained localization in tumor tissue compared to DSPE liposomes. Taken together, our findings suggest that DSPE-PEI liposomes have the potential to be used as effective drug carriers for enhanced intracellular uptake and localization of anticancer drugs in tumor tissue through intratumoral injection.

Multifunctional porous silicon nanoparticles for cancer theranostics

“…administration was still visible after >20 days in animals used in the therapy study, indicating that such sustained release was feasible under the experimental conditions. The intratumorally administered SF showed negligible tumor suppression probably due to the rapid elimination of the small drug molecules from the tumor [40,42]. The antitumor effect was also assessed via H&E staining of the tumor sections ( Fig.…”

“…However, conventional small drug molecules can be rapidly pumped out from the tumor into the bloodstream after intratumoral injection, due to the high pressure environment in the tumor or the proteins that exclude drugs from tumor cells and tissues [40,41]. For example, polymeric nanocarriers and cationic liposomes have been shown to increase the tumor retention of loaded drugs after intratumoral administration [40,42].…”

Therapeutic efficacy of doxorubicin delivery by a CO2 generating liposomal platform in breast carcinoma

“…TSL were prepared by thin-lipid film hydration and the sequential extrusion method [18,19]. The encapsulation of DOX in the aqueous core of the liposomes was achieved by the remote loading method using an ammonium sulfate transmembrane gradient.…”

“…The loading efficiency of DOX into liposomes was measured by UV-vis spectrophotometry (UV-mini, Shimadzu, Japan) at wavelength of 490 nm after dissolution of the liposomes in a chloroform-methanol mixture (8:2, v/v) [19]. In addition, morphologies of TLS-C after both DOX and NH 4 HCO 3 encapsulation were monitored by cryogenic transmission electron microscopy (cryo-TEM, Tecnai G2 Spirit, FEI Company, Hillsboro, OR, USA).…”

NIR responsive liposomal system for rapid release of drugs in cancer therapy

“…[23][24][25][26] In brief, DPPC, Chol, DSPE-PEG 2000 , and Cypate at a molar ratio of 12:8:1:0.8 were dissolved in a mixed solvent of chloroform and methanol (V:V =1:1) and placed in a high vacuum to remove the residual organic solvent. The lipid film was then hydrated using an aqueous (NH 4 ) 2 SO 4 (350 mM) or NH 4 HCO 3 (2.7 M) solution via sonication at ice bath conditions.…”