Improving Penetration in Tumors With Nanoassemblies of Phospholipids and Doxorubicin

Abstract

We have developed a novel PEG-PE-based nanocarrier of doxorubicin that increased cytotoxicity in vitro and enhanced antitumor activity in vivo with low systemic toxicity. This drug packaging technology may provide a new strategy for design of cancer therapies.

Stability Influences the Biodistribution, Toxicity, and Anti-tumor Activity of Doxorubicin Encapsulated in PEG-PE Micelles in Mice

“…The mean diameter of M 1 -DOX made from PEG-PE copolymer was 14.5±1.2 nm, consistent with our previous works (10,11). The increased sizes were observed in the micelles incorporated 33 % (M 2 -DOX) and 50 % (M 3 -DOX) of HSPC, with diameter of 22.4±0.9 nm, and 34.2±1.3 nm, respectively.…”

“…After incubation for 12 h, the cells were washed and collected in ice-cold phosphate-buffer saline for measurement of DOX fluorescence. The fluorescence from individual cells was detected with a flow cytometer (FACS Calibur, BD, San Jose, CA) as described previously (10). For detection of doxorubicin-derived fluorescence, excitation was with the 488 nm line of an argon laser and emission fluorescence between 564 and 606 nm was measured.…”

“…It has been reported that micelles comprised of PEG-PE can load with a variety of poorly soluble drugs such as paclitaxel and tamosifen (8), and are capable of delivering their load into low cutoff size tumor in mice with higher efficiency than even PEGmodified liposomes (9). We have demonstrated the nanoassemblies of PEG-PE and DOX increasing cytotoxicity in vitro and enhancing anti-tumor activity in vivo with low systemic toxicity (10). Recently, we have used a one-step self-assembly procedure to load water-soluble amphiphilic drugs, such as DOX hydrochloride, epirubicin hydrochloride, vinorelbine tartrate and vincristine sulfate, into PEG-PE micelles in aqueous medium.…”

“…Another one is the crosslinked micelles that formed from these polymers with the functionalized groups (14). We have shown that encapsulation of DOX into PEG-PE micelles has a tightly packed structure compared to the PEG-PE micelles without DOX, which allows a longer circulation in plasma and a controlled drug release responded to pH change (10). This is possibly due to the amphiphilic nature of the two molecules as well as their specific structures.…”

PLGA-Based Nanoparticles as Cancer Drug Delivery Systems

“…Different strategies have been used to make a hydrophilic cloud around the nanoparticles and reduce their uptake by RES organs. These strategies comprise coating of nanoparticles with Tween 80 (Gelperina et al, 2002), PEG (polyethylene glycol) (Tang et al, 2007), PEO (polyethylene oxide) (Soppimath et al, 2001), poloxamers and poloxamines (Moghimi and Hunter, 2000;Mozafari et al, 2009), polysorbate 80, TPGS and polysaccharides like dextran (Stolnik et al, 1995;Torchilin and Trubetskoy, 1995;Mahapatro and Singh, 2011). Hydrophilic polymers can be useful at the surface of NPs by adsorption of surfactants or by utilize of block copolymers or branched copolymers (Stolnik et al, 1995;Storm et al, 1995;Torchilin and Trubetskoy, 1995;Mahapatro and Singh, 2011).…”