Surface Engineering of Liposomes for Stealth Behavior

Nag, Okhil K.; Awasthi, Vibhudutta

doi:10.3390/pharmaceutics5040542

Cited by 253 publications

(190 citation statements)

References 172 publications

(236 reference statements)

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“…The negative surface charge of DTXPL could be contributed by negatively charged phosphate group of PEG-DSPE which is in accordance with the previous report [31]. Sustained release of DTX from stable and long circulating liposomes is extremely important to achieve EPR dependent passive targeting of tumor [32][33][34].…”

Section: Oral Telmisartan Controlsupporting

confidence: 83%

Tumor Stromal Disrupting Agent Enhances the Anticancer Efficacy of Docetaxel Loaded PEGylated Liposomes in Lung Cancer

Patel

Doddapaneni

Chowdhury

et al. 2016

Nanomedicine (Lond.)

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Aim: Therapeutic efficacy of anticancer nanomedicine is compromised by tumor stromal barriers. The present study deals with the development of docetaxel loaded PEGylated liposomes (DTXPL) and to investigate the effect of tumor stroma disrupting agent, telmisartan, on anticancer efficacy of DTXPL. Methods: DTXPL was prepared using proprietary modified hydration method. Effect of oral telmisartan treatment on tumor uptake of coumarin-6 liposomes and anticancer efficacy of DTXPL was evaluated in orthotopic xenograft lung tumor bearing mice. Results: DTXPL (105.7 ± 3.8 nm) showed very high physical stability, negligible hemolysis, 428% enhancement in bioavailability with significantly higher intratumoral uptake. Marked reduction in collagen-I, MMP2/9 and lung tumor weight were observed in DTXPL+telmisartan group. Conclusion: Combination of DTXPL with telmisartan could significantly enhance clinical outcome in lung cancer. Lung cancer is by far the most common cause of cancer related mortality in both men and women. Non-small-cell lung cancer (NSCLC) accounts for 87% of total cases of lung cancer with overall 5-year survival rate less than 18.2% [1,2]. Depending on the stage of lung cancer and condition of patients, the chemotherapeutic regimen for lung cancer includes following drugs: Cisplatin/carboplatin or paclitaxel/docetaxel, etoposide, vinorelbine, erlotinib or other tyrosine kinase inhibitors, gemcitabine and pemetrexed. Despite recent advances in diagnosis and treatment, the clinical outcome amongst NSCLC patients is still not impressive. Docetaxel (DTX) is one the most widely used for drug for the treatment of various types of solid tumor including ovarian, breast, lung and head/neck cancers. Docetaxel has extremely poor water solubility and rapid precipitation tendency, which necessitates very high concentration of ethanol and surfactant for its intravenous injection. Tween 80 in Taxotere ® formulation is responsible for severe life threatening hypersensitivity and peripheral neuropathy [3,4]. A safer formulation to enhance patient compliance and therapeutic efficacy of DTX is always in demand. As a result, current research is mainly focused on developing nanomedicinal formulation such as liposomes, polymeric micelles, albumin nanoparticles, polymer drug conjugates, etc. Liposomes are the most versatile nanocarrier with superior biocompatibility and large scale manufacturing feasibility compared to other types of nanocarrier. Abraxane ® ,

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Section: Oral Telmisartan Controlsupporting

confidence: 83%

Tumor Stromal Disrupting Agent Enhances the Anticancer Efficacy of Docetaxel Loaded PEGylated Liposomes in Lung Cancer

Patel

Doddapaneni

Chowdhury

et al. 2016

Nanomedicine (Lond.)

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“…[16][17][18][19][20] The issue of micelle contamination and controlling the orientation of the anchors are major impediments to such an evaluation. Currently, three methods are in widespread use for modifying the liposomal surface.…”

Section: -9)mentioning

confidence: 99%

“…Currently, three methods are in widespread use for modifying the liposomal surface. 11,15,16) These methods include the pre-insertion method, the post-insertion method, and surface reaction modification. The first two methods result in quite different liposomal surface topologies, namely, the orientation of the ligand and its density.…”

mentioning

confidence: 99%

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

Lee

Sato

Hyodo

et al. 2016

Biological & Pharmaceutical Bulletin

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The surface topology of ligands on liposomes is an important factor in active targeting in drug delivery systems. Accurately evaluating the density of anchors and bioactive functional ligands on a liposomal surface is critical for ensuring the efficient delivery of liposomes. For evaluating surface ligand density, it is necessary to clarify that on the ligand-modified liposomal surfaces, some anchors are attached to ligands but some are not. To distinguish between these situations, a key parameter, surface anchor density, was introduced to specify amount of total anchors on the liposomal surface. Second, the parameter reaction yield was introduced to identify the amount of ligand-attached anchors among total anchors, since the conjugation efficiency is not always the same nor 100%. Combining these independent parameters, we derived: incorporation ratio surface anchor density reaction yield. The term incorporation ratio defines the surface ligand density. Since the surface anchor density represents the density of polyethylene glycol (PEG) on the surfaces in most cases, it also determines liposomal function. It is possible to accurately characterize various PEG and ligand densities and to define the surface topologies. In conclusion, this quantitative methodology can standardize the liposome preparation process and qualify the modified liposomal surfaces.Key words active targeting; surface ligand density; incorporation ratio; surface anchor density; reaction yield; surface topology Nanotechnology has the capability to deliver drugs to specific cell types, but it is important to maximize therapeutic effects and minimize unexpected adverse effects, for this technology to be effectively used.1-4) In using nanoparticles for specific drug delivery, they need to have both a stealth function to prevent non-specific recognition by the reticuloendothelial system (RES), 5,6) and an active targeting function to allow them to bind to the specific cell type of interest. 7-9)Polyethylene glycol (PEG) modification is frequently used to confer a stealth function to nanoparticles. 5,6,10) For active targeting, specific ligands for bioactive molecules such as nucleic acids, peptides, proteins, and antibodies are attached to the surface of nanoparticles via a PEG spacer.11) Many attempts have been made to develop various types of specific ligands for use in active targeting, which is critical for targeting non-fenestrated tissues such as the brain, lung and related tissues. [12][13][14] The procedures used to prepare ligands that are used in modifying nanoparticles are relatively complicated because this increases the number of steps in the preparation process that can lead to conditions where ligand molecules can be unstable.15) Therefore, optimal reaction (modification) conditions and methods for quantifying the density of the attached ligand that is attached to the nanoparticles need to be evaluated precisely.Problems are usually encountered in evaluating both the density of the liposomal ligands and the PEG, since a variety of m...

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“…Liposomal carriers, in particular, have received considerable attention over the years due to their ease of formation, tailorable surface functionalities and excellent cell internalization (Immordino et al, 2006;Kong et al, 2012;Nag & Awasthi, 2013). Cationic liposomes prepared with 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and dioleoyl phosphatidylethanolamine (DOPE) lipids have been found to be highly efficient in complexing the si-RNA and have been evaluated for their silencing efficacy in Many cancer cell lines (Ying & Campbell, 2014).…”

Section: Introductionmentioning

confidence: 99%

EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

et al. 2014

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Background: RNA interference (RNAi) technology using short interfering RNA (si-RNA) has shown immense potential in the treatment of cancers through silencing of specific genes. Cationic non-viral vectors employed for gene delivery exhibit toxic effects in normal cells limiting their widespread use, therefore, site-specific delivery using benign carriers could address this issue. Objective: Design of a non-toxic carrier that enables site-specific delivery of si-RNA into the cancer cells is of prime importance to realize the promise of gene silencing. Methods: In the present study, non-cationic liposomes encapsulating si-RNA against epithelial cell adhesion molecule (EpCAM) were developed and characterized for encapsulation efficiency, colloidal stability, in vitro and in vivo gene silencing efficacy. Results: PEGylated liposomes containing phosphatidyl choline and phosphatidyl ethanolamine exhibited maximum si-RNA encapsulation efficiency of 47%, zeta potential of -21 mV, phase transition temperature of 51 C and good colloidal stability in phosphate-buffered saline (PBS) containing bovine serum albumin (BSA) and plasma protein (PP) at 37 C. Conjugation of epithelial cell adhesion molecule (EpCAM) antibody to the liposomes resulted in enhanced cell internalization and superior down-regulation of EpCAM gene in MCF-7 cell lines when compared with free si-RNA and the non-targeted liposomes. In vivo evaluation of immunoliposomes for their efficacy in regressing the tumor volume in Balb/c SCID mice showed about 35% reduction of tumor volume in comparison with the positive control when administered with an extremely low dose of 0.15 mg/kg twice a week for 4 weeks. Conclusion: Our results exhibit that the nanocarrier-mediated silencing of EpCAM gene is a promising strategy to treat epithelial cancers.

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Surface Engineering of Liposomes for Stealth Behavior

Cited by 253 publications

References 172 publications

Tumor Stromal Disrupting Agent Enhances the Anticancer Efficacy of Docetaxel Loaded PEGylated Liposomes in Lung Cancer

Tumor Stromal Disrupting Agent Enhances the Anticancer Efficacy of Docetaxel Loaded PEGylated Liposomes in Lung Cancer

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

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