m-dPEG®₂₅-DSPE

Liposomes and Micelles

As carriers of cytotoxic agents, labels, and imaging agents, liposomes and micelles have revolutionized pharmaceutics and medical diagnostics. Operating either passively or actively through ligand-receptor targeting, liposomal and micellar nanoparticles with diameters of 30 – 200 nm possess several desirable features for payload delivery. These features include good stability in vivo and in vitro; extended circulation in the bloodstream, increased tumor accumulation through the enhanced permeability and retention (EPR) effect; and reduced systemic toxicity, since cytotoxic agents are sequestered from cells until delivery through membrane fusion. To date, several different liposomal and micellar formulations have been approved for clinical use.

In vivo, liposomes and micelles used as nanocarriers are susceptible to opsonization and removal from the bloodstream through the RES, also known as the mononuclear phagocytic system (MPS). Polyethylene glycol (PEG) is the most commonly used surface coating of liposomes and micelles and is considered the gold standard for modifying head groups of lipids used in liposomes and micelles. Covalent attachment of PEG (PEGylation) to liposomal and micellar surfaces provides a “stealth” character to the coated surfaces. A sufficiently dense coating of PEG creates a hydrophilic, flexible, steric barrier around the PEGylated liposomes and micelles, thus preventing opsonin proteins from binding to the liposomal/micellar surface (opsonization). Consequently, liposomes and micelles circulate longer in the bloodstream, which therefore results in lower dosing requirements.

PEGylation of Liposomes and Micelles

Traditional PEG is a polymer. Accordingly, polymeric PEG is dispersed (Đ > 1) and consists of a complex mixture of different chain lengths and molecular weights. In contrast, Quanta BioDesign’s dPEG^® products are single molecular weight compounds. Each dPEG^® product contains a single, discrete PEG chain (Đ = 1). This results in a uniform product that is easier to analyze and use.

Traditionally liposomes and micelles are coated with polymeric PEG₂₀₀₀ (a polymer PEG having an average molecular weight of 2,000 Daltons) at a density of about 5 – 8 mole%. Three papers from the lab of Başar Bilgiçer at the University of Notre Dame demonstrate that this traditional PEG coating is not scientifically well reasoned. Using Quanta BioDesign’s dPEG^® products, two papers by Stefanik, et al., and one paper by Noble, et al., analyze systematically the effect of different PEG chain lengths and different degrees of PEGylation of liposomes. The results of this research demonstrate that smaller, dPEG^® coatings provide PEGylated liposomes with levels of protection similar to polymeric PEG₂₀₀₀. Furthermore, liposomes modified with dPEG^® coatings showed superior uptake of PEGylated liposomes as compared to liposomes PEGylated with traditional polymeric PEG₂₀₀₀.

PN11373, m-dPEG^®₂₅-DPSE

With PN11373, m-dPEG^®₂₅-DSPE, the phospholipid DSPE is modified by addition of a non-reactive methoxy-terminated dPEG^® that is 77 atoms (99.3 – 100.3 Å) long. It can be used as a standalone surface coating of liposomes and micelles to provide protection from opsonization and removal by the RES. In addition, reasoning from the data in the above-mentioned papers from the Bilgiçer lab, m-dPEG^®₂₅-DSPE can be mixed with other DSPE products from Quanta BioDesign that are coated with slightly longer dPEG^® spacers and terminated with reactive groups (for example, maleimide, TFP ester) that can be modified by conjugation to targeting agents such as ligand-targeting peptides, antibodies, or antibody fragments or to small molecule drugs.

If you need bulk product in a larger package size than our standard sizes, please contact us for a quote. Our commercial capabilities permit us to manufacture this product at any scale that you need.

Application References:

1. Hermanson, G. T. Chapter 18, PEGylation and Synthetic Polymer Modification. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 787-838. Click here now for a review of Greg’s book and a link to purchase it.
2. Hermanson, G. T. Chapter 21, Liposome Conjugates and Derivatives. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 921-949.
3. Stefanick, J. F.; Ashley, J. D.; Kiziltepe, T.; Bilgicer, B. A Systematic Analysis of Peptide Linker Length and Liposomal Polyethylene Glycol Coating on Cellular Uptake of Peptide-Targeted Liposomes. ACS Nano 2013, 7(4), 2935–2947. https://doi.org/10.1021/nn305663e.
4. Stefanick, J. F.; Ashley, J. D.; Bilgicer, B. Enhanced Cellular Uptake of Peptide-Targeted Nanoparticles through Increased Peptide Hydrophilicity and Optimized Ethylene Glycol Peptide-Linker Length. ACS Nano 2013, 7(9), 8115–8127. https://doi.org/10.1021/nn4033954.
5. Noble, G. T.; Stefanick, J. F.; Ashley, J. D.; Kiziltepe, T.; Bilgicer, B. Ligand-Targeted Liposome Design: Challenges and Fundamental Considerations. Trends in Biotechnology 2014, 32(1), 32–45. https://doi.org/10.1016/j.tibtech.2013.09.007.
6. Saw, P. E.; Park, J.; Lee, E.; Ahn, S.; Lee, J.; Kim, H.; Kim, J.; Choi, M.; Farokhzad, O. C.; Jon, S. Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes. Theranostics 2015, 5(7), 746–754. https://doi.org/10.7150/thno.10732.
7. Bulbake, U.; Doppalapudi, S.; Kommineni, N.; Khan, W. Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics 2017, 9(2), 12. https://doi.org/10.3390/pharmaceutics9020012.