Liposomes stabilization

For liposomes with bilayers in either the gel or fluid state, hydrolysis kinetics could be adequately described by the Arrhenius equation (Fr kjaer et al., 1984 Grit et al., 1989). This finding opens the opportunity to perform accelerated stability tests to predict liposome stability at ambient temperatures or in the refrigerator provided that no fluid-to-gel transition of the bilayer occurs in the temperature range under investigation. 

Figure 6 Encapsulation of plasmid DNA (pDNA) in small sterically stabilized liposomes [stabilized plasmid-lipid particles (SPLP)] using a detergent dialysis procedure. (A) Entrapped pDNA-to-lipid ratio as a function of the initial pDNA-to-lipid ratio (mg/mg). The initial lipid concentration was lOmg/mL. (B) Cryo-electron micrograph showing the structure of SPLP. The location of the plasmid is indicated by the striated pattern superimposed on the liposomes. The bar represents 100 nm.

Ogawa, Y, H. Kawahara, N. Yagi, M. Kodaka, T. Tomohiro, T. Okada, T. Konakahara, and H. Okuno, Synthesis of a novel lipopeptide with alpha-melanocyte-stimulating hormone peptide ligand and its effect on liposome stability [published erratum appears in Lipids, 1999 34(6) 643]. Lipids, 1999. 34(4) 387-94. 

Ge L, Mohwald H, Li J (2003) Phospholipid liposomes stabilized by the coverage of polyelectrolyte. Colloids Surf A Physicochem Eng Aspects 221 49-53... 

Membrane Lipid composition modification Increased liposome stability,... 

As mentioned above, the ability to adsorb to the cornea and an optimal drug release rate have been defined as the two liposomal attributes most responsible for increasing bioavailability after topical ocular administration. A number of factors, including drug encapsulation efficiency, liposome size and charge, distribution of the drug within liposomes, stability of liposomes in the conjunctival sac and ocular tissues, their retention in the conjunctival sac, and most importantly their affinity toward the corneal surface and the rate of release of the encapsulated drug, have... 

Barber, R.F. Shek, P.N. Liposome Stability during Ultrasonic Nebulization., Proceedings of the 33rd Harden... 

Fig. 4. Blood concentration (percentage of injected dose) versus time curves of DOPE CHEMs liposomal formulations following intravenous injection in rats noncoated liposomes (open squares), liposomes containing 5 mol% of PEG(2000)-DSPE (circles) and (DDGG)4(E0) 4 (diamonds). Each data point represents the arithmetic mean standard deviation (n=3). As the results show the most important property of the liposomes stabilized with 5 mol % (DDGG)4(E0) 4 is its excellent blood circulation versus both plain and DSPE-PEG(2000) stabilized vesicles. (Reproduced from ref. 38 with permission from Elsevier)...

Guo X, MacKay JA, Szoka FC Jr (2003) Mechanism of pH-triggered collapse of phos-phatidylethanolamine liposomes stabilized by an ortho ester polyethyleneglycol lipid. Biphys J 84 1784-1795... 

There is a need for tight control of manufacturing parameters, particularly liposome size, uniformity of liposomes, stability of bioactive drugs during the encapsulation process, sterility and endotoxin control. Hydrophilic drugs are easily encapsulated, but lipophyllic drugs may need to be modified to render them encapsulate. 

Winterhalter, M., Lasis, D.D., 1993. Liposome stability and formation Experimental parameters and theories on the size distribution. Chem. Phys. Lipids, 64, 35-43. 

The bioflavor compounds of blue cheese, obtained from fermentation of Aspergillus spp., were encapsulated in soy lecithin liposomes and spray-dried to obtain the powder form by Santana et al. (2005). A sensory evaluation was performed, by adding the liposome-bioflavor powder in a base of light cream cheese, which was spread on toasts. Flavor intensity, acceptance by the consumers, and purchasing intention were the tests done in the sensory evaluation. The results showed that the encapsulation maintained the characteristic flavor of blue cheese and the product was classified by the consumers as acceptable. The dried liposome-stabilized flavor was useful to add in foods and to be kept in storage. 

In pursuit of enhanced liposomal stability, Ringsdorf, Regen, Chapman, and O Brien pioneered the use of polymerized liposomes. These liposomes were prepared from polymerizable lipid molecules. Polymerized liposomes demonstrated uniform size distribution and are considerably more stable compared to their unpolymerized counterparts. Various polymerizable groups (e.g., butadiene, dia-cetylene, vinyl, or methacryloyl ) have been used to achieve the polymerization of the lipid bilayers. These reactive groups on the lipid may be in the head group region, the hydrocarbon core, or at the hydrocarbon termini. 

In our laboratory, we have prepared stable freeze-dried liposomes containing two antiasthma drugs, namely beclomretasone dipropionate (BDP) and salbutamol sulfate (SS) [44]. The highest liposome stability on rehydration, demonstrated by minimized increases in size measurements (Zaverage) and polydispersity index (PI), was shown when sucrose was employed as a cryoprotectant (Figure 15.3). By contrast, when no cryoprotectant was included, liposome size was increased by approximately 30 times, indicating that SUVs were massively aggregated or converted into MLVs [44]. 

Over 40 years since it what found that phospholipids can form closed bilayered structures in aqueous systems, liposomes have made a long way to become a popular pharmaceutical carrier for numerous practical applications. Liposomes are phospholipid vesicles, produced by various methods from lipid dispersions in water. Liposome preparation, their physicochemical properties and possible biomedical application have already been discussed in several monographs. Many different methods exist to prepare liposomes of different sizes, structure and size distribution. The most frequently used methods include ultrasonication, reverse phase evaporation and detergent removal from mixed lipid-detergent micelles by dialysis or gel-filtration. To increase liposome stability towards the physiological environment, cholesterol is incorporated into the liposomal membrane (up to 50% mol). The size of liposomes depends on their composition and preparation method and can vary from... 

Liposomes as a dosage form allow for a broad variety of administration routes. In addition to the most traditional and frequent parenteral (intravenous) way of administration, some alternative approaches are also developed or under development, although each of these approaches has its own problems and limitations. Thus, oral administration requires high liposome stability and drug delivery from the gut to the blood with subsequent drug release. Early attempts with polymerized liposomes as potential oral vaccine carriers were only partially successful. Currently, many alternative schemes are under development. 

Ogawa Y, Kawahara H, Yagi N et al (1999) Synthesis of a novel lipopeptide with a-melanocyte-stimulating hormone peptide ligand and its effect on liposome stability. Lipids 34 387-394... 

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