Polymer Lipospheres

The influence of phospholipid content on drug encapsulation and release has been examined both for classic lipospheres having a lipid core and for polymer lipospheres having a polymer core [35,37],... 

Reithmeier investigated the influence of fat/phospholipid ratio to improve drug encapsulation efficiency into microparticles prepared by the solvent evaporation method [37], A cosolvent-solvent evaporation method like the one described above for the preparation of polymer lipospheres [35] was used. Here, somatostatin as a model peptide was dissolved in methanol and added to a solution of the lipid components in hexane [37],... 

The internal hydrophobic core of lipospheres is composed of fats and biodegradable polymers, mainly triglycerides and lactide-based polymers, whereas the surface activity of liposphere particles is provided by the surrounding lecithin layer, composed of phospholipid molecules. 

All liposphere formulations prepared remained stable during the 3-month period of the study, and no phase separation or appearance of aggregates were observed. The difference between polymeric lipospheres and the standard liposphere formulations is the composition of the internal core of the particles. Standard lipospheres, such as those previously described, consist of a solid hydrophobic fat core composed of neutral fats like tristearin, whereas, in the polymeric lipospheres, biodegradable polymers such as polylactide or polycaprolactone were substituted for the triglycerides. Both types of lipospheres are thought to be stabilized by one layer of phospholipid molecules embedded in their surface. 

Amselem, S., C.R. Alving, A.J. Domb, Polymeric Biodegradable Lipospheres as Vaccine Delivery Systems, Polymers for Advanced Technologies, 3, 351, 1992. 

Particles resulting from the o/w method were found to have a size of 100 nm. After washing, an incorporation of 5.2% peptide was obtained, with recovery being 47% compared to 1.7% incorporated peptide, and 63% recovery with the w/o/w method particle size was 200 nm. Release experiments with lipospheres containing a lipid core have shown sustained release ranging from a few hours to several days. The preferred core material for delayed release, according to Domb, is a polymer such as polylactide [1],... 

To create lipospheres using polymers, the same melt dispersion as described above has successfully been applied for the formation of antigen-loaded lipospheres using a 1 1 (w/w) ratio for phospholipid and polymer [20],... 

An attempt was made to prepare peptide-loaded lipospheres according to Domb s description of antigen encapsulation [1], where a thin film of polymer, phospholipid, and drug is formed after evaporation of organic solvent, and lipospheres are created by adding warm buffer solution and mixing. This resulted only in the formation of large particles at low yield. 

Polymers with a molecular weight above 50,000 Da did not form uniform particles, and therefore L-poly(lactic acid) (L-PLA, Mw 2000), poly(lactic-co-gly-colic acid) (PLGA, 75 25, 15,000 Da), and PLGA (50 50, 23,000 Da) were chosen for further investigation. Only L-PLA showed good entrapment efficiencies (80% for triptorelin and >50% for leuprolide). PLGA failed to entrap more than 10% in both cases. In comparison, microspheres were produced that differ from the lipo-sphere preparation only in that the solid hydrophobic core of the lipospheres is stabilized by a monolayer of phospholipid molecules embedded in its surface. All liposphere particle diameters were smaller compared to those of the microspheres. 

Rasiel investigated triptorelin release profiles from lipospheres made from L-PLA, PLGA 50 50, and PLGA 75 25 [35], Although both PLGA polymers showed a burst release within the first 24 h, L-PLA released the peptide for over 30 d (Figure 4.6). 

FIGURE 4.6 Effects of polymer type on the cumulative release of triptorelin from lipospheres. Lipospheres were prepared from L-PLA (solid squares), PLGA 50 50 (open circles), or PLGA 75 25 (filled triangles) with HSPC in a 1 6 phospholipid/polymer ratio. Triptorelin (4 mg) was dissolved in N-methylpyrrolidone (500) p,L and mixed with a chloroformic solution of L-PLA and HSPC (1 mL). The release experiment was performed in pH 7.4 phosphate buffer, at 37°C, and analyzed by HPLC. (Adapted from [35] with permission from Wiley Sons.)... 

Effect of Synthetic Polymers on the Production of Lipospheres by Solvent Evaporation... 

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