Microencapsulated liposomes

The potential of liposomes in oral drug delivery has been largely disappointing. However, the use of polymer-coated, polymerized, and microencapsulated liposomes have all increased their potential for oral use [63], and it predicted that a greater understanding of their cellular processing will ultimately lead to effective therapies for oral liposomes. 

The liposomes did not interfere with alginate capsule formation and were retained within the finished capsules. When myoglobin (used as a model protein) was not entrapped within liposomes but was simply enclosed as "free" protein within the coated alginate beads, 60% of it diffused out of the capsule over the first two days. In contrast, delayed release was achieved with microencapsulated liposomes containing myoglobin. Very little myoglobin appeared outside the capsules until 10 days after the start of the release experiment. It required a further 12 days to reach a level of 60% and not until 50 days after the start of the experiment was 100% release achieved. (Figure 5)... 

When the microencapsulated liposomes are left untreated the lipid bilayer provides a barrier to diffusion through which the entrapped protein does not pass until the liposomes gradually become leaky, primarily due to oxidation of the phospholipid side chains. This mechanism results in a delayed release. Triton or sonic treatment of the microencapsulated liposomes provide pulsed re ease. Since both detergent and sonication disrupt lipid bi ayers, the mechanism by which pulsed release is achieved may be that these stimuli initially disrupt the liposomes and then the lipid reforms around some of the protein solution inside the capsule, possibly in an altered lamellar form alternatively, the treatment could disrupt only the more susceptible liposomes, leading to two phases of release, first from the freed protein and later from protein that remained liposome-entrapped. 

Kibat, P. G., Igari, Y., Wheatley, M. A., et al. Enzymatically activated microencapsulated liposomes can provide pulsatile drug release. Faseb J. 4 2533—2539, 1990. 

Dhoot, N. O., and Wheatley, M. A. (2003), Microencapsulated liposomes in controlled drug delivery Strategies to modulate drug release and eliminate the burst effect, /. Pharm. Sci., 92(3), 679-689. 

Machluf M, Regev O, Peled Y, et al. Characterization of microencapsulated liposome systems for the controlled delivery of liposome-associated macromolecules. / Control Release 1997 43 35 5. 

Intracorporeal applications are far more complex the enzyme should be directed to its target within the patient s body and avoid the immune response. Immobilization to biocompatible supports may reduce the immune response significantly (Klein and Langer 1986). Several systems for enzyme delivery have been envisaged microencapsulation, liposome entrapment (Chen and Wang 1998 Fonseca et al. 2003), microencapsulation (Dai et al. 2005) and artificial red blood cell ghosts (Serafini et al. 2004). An updated review on the subject has been published... 

Cortesi, R., Esposito, E., Gambarin, S., Telloli, P., Menegatti, E., and Nastruzzi, C., Preparation of liposomes by reverse-phase evaporation using alternative organic solvents, Journal of Microencapsulation, 1999, 16, 251-256. 

Filipovic-Grcic, J., Skalko-Basnet, N., and Jalsenjak, I. (2001). Mucoadhesive chitosan-coated liposomes Characteristics and stability. ]. Microencapsul. 18, 3-12. 

In this case, unilamellar vesicles with a large capture volume were prepared by the reverse phase evaporation technique and alginate was used to microencapsulate the liposome s. The alginate spheres were double coated, first with poly-L-lysine and then with polyvinyl amine (Wheatley and Langer in press). 

Farshi, F.S., et al. 1996. In-vivo studies in the treatment of oral ulcers with liposomal dexametha-sone sodium phosphate. J Microencapsul 13 537. 

Singh, M., et al. 1993. Liposomal drug delivery to the eye and lungs A preliminary electron microscopy study. J Microencapsul 10 35. 

C. Bealulac, S. Clement-Major, J. Hawar, and J. Lagace, In vitro kinetics of drug release and pulmonary retention of microencapsulated antibiotic and liposomal formulations in relation to lipid composition,. /. Microencapsulation 14 335... 

Foldvari, M., Effect of vehicle on topical liposomal drug delivery petrolatum bases, J. Microencapsul., 13, 589, 1996. 

Current research in this area involves numerous new and novel systems, many of which have strong therapeutic potential. In this chapter, we have tried to emphasize the importance of oral routes as well as others, such as ocular, transdermal, intrauterine, and vaginal. The various microencapsulation, nanoencapsulation, and liposome technologies and the release of drugs and bioactive compounds from such products have been described. 

Vyas, S. P., Singh, R., Asati, R. K. (1995), Liposomally encapsulated diclofenac for sono-phoresis induced systemic delivery, / Microencapsul., 12,149-154. 

Zeisig, R., and Cammerer, B. (2001). Liposomes in the food industry. In P. Vilstrup (ed.). Microencapsulation of Food Ingredients. Leatherhead Publishing, Surrey, UK, pp. 101-119. 

Torchilin, VP. Polymer-coated long-circulating microparti-culate pharmaceuticals. J. Microencapsul. 1998,75(1), 1-19. Lasic, D.D., Martin, F., Eds. Stealth Liposome CRC Press Boca Raton, FL, 1995. 

Formulation and/or development of advanced drug-delivery systems such as microencapsulated molecules, transdermal patches, or liposomes are frequently accomplished in the laboratory. However, large-scale production of these dosage forms may be problematic because the same conditions of manufacture may not be attainable or desirable in the plant setting. Consultation with process development personnel during the finalization of the prototype development phase is one way of minimizing scale-up difficulties. 

Kim CK, Han JH (1995) Lymphatic delivery and pharmacokinetics of methotrexate after intramuscular injection of differently charged liposome-entrapped methotrexate to rats. J Microencapsul 12 437-4 46... 

Liang W, Levchenko TS, Torchilin VP (2004) Encapsulation of ATP into liposomes by different methods Optimization of the procedure. J Microencapsul 21 251-261... 

Kim HY, Baianu IC (1991) Novel liposome microencapsulation techniques for food applications. Trends Food Sci Technol 2 55-61... 

Cortesi R, Esposito E, Gamharin S, Telloli P, Menegatti E, Nastruzzi C (1999) Preparation of liposomes hy reverse-phase evaporation using alternative organic solvents. J Microencapsul 16 251-256... 

NiiT,IshiiF (2005) Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method. Int J Pharm 298 198-205... 

Enzymes may be immobilized by encapsulation in nonpermanent (e.g., liposomes) or permanent (e.g., nylon) microcapsules. The enzyme is trapped inside by a semi-permeable membrane, where substrates and products are small enough to freely diffuse across the boundary. While nonpermanent microcapsules are useful in biochemical research, only permanent microencapsulations yield analytically useful systems, because of their mechanical stability. 

Meisner D, Pringle J, Mezei M. Liposomal pulmonary drug delivery. I. In vivo disposition of atropine base in solution and liposomal form following endotracheal instillation to the rabbit lung. J Microencapsul 6(3) 379-387, 1989. 

Vyas SP, Sakthivel T. Pressurized pack-based liposomes for pulmonary targeting of isoprenaline—development and characterization. J Microencapsul ll(4) 373-380, 1994. 

Kulkarni SB, Betageri GV, Singh M. Factors affecting microencapsulation of drugs in liposomes. J Microencapsul 12(3) 229-246, 1995. 

Velpandian T, Gupta SK, Gupta YK, et al. Ocular drug targeting by liposomes and their corneal interactions. J Microencapsul 1999 16 243-250. 

Kirby CJ, Gregoriadis G. Preparation of liposomes containing factor VIII for oral treatment of haemophilia. J Microencapsul 1984 1 33 5. 

The term encapsulation has been used to distinguish entrapment preparations in which the biocatalyst environment is comparable to that of the bulk phase and where there is no covalent attachment of the protein to the containment medium (Fig. 6-1 D)[21J. Enzymes or whole cells may be encapsulated within the interior of a microscopic semi-permeable membranes (microencapsulation) or within the interior of macroscopic hollow-fiber membranes. Liposome encapsulation, a common microscopic encapsulation technique, involves the containment of an enzyme within the interior of a spherical surfactant bilayer, usually based on a phospholipid such as lecithin. The dimensions and shape of the liposome are variable and may consist of multiple amphiphile layers. Processes in which microscopic compart-mentalization (cf. living cells) such as multienzyme systems, charge transfer systems, or processes that require a gradient in concentration have employed liposome encapsulation. This method of immobilization is also commonly used for the delivery of therapeutic proteins. 

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