A comment in the stead of an anwer.
Tamoxifen is a rather lipophilic drug (the reported log P = 3.68 at pH = 7), and therefore associates with lipid vesicles predominantly by insertion into the vesicle forming bilayer(s); encapsulation into the aqueous core does not play a significant role for the drug. Fluid bilayers are far better suited for this kind of association than bilayers in an ordered (e.g., gel) phase, which is the form adopted by DSPC at temperatures below 49 °C. You should therefore seriously reconsider your lipid choice before investing further work into the project, which might otherwise turn out to be a futile effort. (Depending on the final aim of the project, you will be better served with partially unsaturated or shorter chain phosphatidylcholines, if you wish to continue using PC. In such a situation, you should replace DSPC with POPC / DOPC or DMPC / DLPC?, respectively, to name but the commercially best available such suitable compounds. Otherwise, you could use non-phospholipid, vesicle forming amphipats to the same effect.
If he's using the thin lipid hydration method he could perform the production at temperatures above the Tc of the lipid in order to encapsulate the hydrophobic compound. Fluid lipids are kind of complicated during storage.
I disagree. The chief problem is not how to get tamoxifen into a DSPC bilayer but rather how to get, and keep, enough of the drug homogeneously distributed in the bilayer over a practically meaningful duration of time.
Owing to size incompatibility between the relatively long, and tightly packed, stearoyl-chains (length ~2.4 nm / chain; Phospholipids Handbook, G. Cevc, ed., M. Dekker, New York) and of tamoxifen (the longest dimension ~ 0.96 nm; http://www.chemicalize.org/structure/#!mol=tamoxifen&source=fp) the drug does not fit well into the bilayer, which has therefore the tendency to squeez out tamoxifen into drug-rich domains that sooner or later precipitate out of a bilayer, and then finally fall-out of vesicular dispersion.
Morever, contrary to David's remark, fluid lipids yield PHYSICALLY more stable dispersions than lipids with ordered, gel phase chains; this is owing to better hydration of the former compared to the latter. Vesicles with ordered aliphatic chains are therefore more apt to aggregate, or even form crystals during long-term storage (in case of DSPC at T the lowest hydrolysis) and minimise the starting free radicals concentration and air/oxygen concentration / volume in your dispersion / vial / primary packaging material when using unsaturated lipids (->to slow down their oxidation) for optimum overall chemical stability of a dispersion.
As an aside, it is energetically expensive to make a dispersion at high temperature (T > 60 °C, i.e., at least 5 °C above the chain melting temperature, Tm) needed to fluidise fatty chains and to avoid too many defects (which peak at T~Tm). Such preparation conditions are also often poorly tolerated by at least some dispersion components. Moreover, thin film method is applicable at laboratory scale only and not upscalable. Such preparation method is therefore of academic interest, merely.
I agree. I guess the drawbacks are the stated: high energy input, not upscalable and just for merely academic purposes. What do you think of encapsulating dexamethasone, curcumin and vitamin D in DSPC liposomes? Do you have some references of what yo are saying? I'm preparing liposomes of DSPC, stearylamine and those drugs. On the other hand, what should be the proper storage of DSPC liposomes? Thanks a lot!
My comments and recommendations are not limited to tamoxifen. One can apply them to any other molecular kind, muitatis mutandis. Curcumin, for example, is longer (in 1-1.6 nm range, according to calculations), but has polar groups / atoms (oxygens) distributed more evenly along the molecule, which is also 'more flexible' (due to lack of rings in its middle region). Unlike tamoxifen, I am therefore expecting curcumin to bind in interfacial region, which is less problematic than binding deeper into a bilayer.
Stearylamine, to my knowledge, is not a drug, but practically an 'unpleasant component' of otherwise neutral or negatively charged bilayers. Whereas its saturation limit is quite high (owing to H-bonding ability and net charge of SA), its cationic nature causes the resulting vesicles to stick to biomembranes and biomacromolecules (that are normally negatively charged). Cationic vesicles are hence generally relatively toxic.
PC vesicles, even in a fluid phase, can accomodate only a small amount of typical glucocorticosteroids, including dexamethasone, for reasons similar to those pertaining to tamoxifen.
As specified earlier, DSPC is a difficult molecule to work with as it, slowly but surely, tends to crystalise at its subtransition temperature of 28.2 °C. Hydrogenated soybean PC (which has also predominantly but not exclusively stearic chains) dos not have this problem and is therefore preferable to DSPC when wishing to use vesicles with relatively densely packed (ordered) and thick bilayers.
Papers supporting essentially each of the statements and recommendations in my first answer to your comment are in public domain. You will find them on Scholar Google, if using the right key words. Re-address me for one or two most important ones (to you), should you face otherwise unsurmountables problems during your search (which will surely teach you many more things).
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