Lipid-based vehicles

Zarif L, Mannino RJ. Cochleates lipid-based vehicles for gene delivery-concept, achievements and future development. In Kluwer H, ed. Cancer Gene Therapy Past Achievements and Future Challenges. New York Academic/Plenum Publishers, 2000 83. 

Therefore, for compounds with good oil solubility, emulsion-based systems, especially lipid-based vehicles, can be used successfully. 

Humberstone, A.J. and Charman, WN. (1997) Lipid-based vehicles for the oral delivery of poorly water soluble drugsAdv. Drug Del. Rev., 25 103-128. 

An increasing body of evidence has shown that certain lipids and excipients found in many lipid-based formulations are capable of inhibiting both P-gp mediated drug efflux and presystemic metabolism in the enterocyte. This inhibition may increase the bioavailability of a drug coadministered with such lipid-based vehicle. 

M. Bojrup, Z. Qi, S. Bjorkman, O. Ostraat, B. Landin, H. Ljusberg-Wahren, and H. Ekberg, Bioavailability of cyclosporine in rats after intragastric administration a comparitive study of the L2 phase and two other lipid-based vehicles, Transplant. Immunol. 4 313-317 (1996). 

Weiner, A.L. Developing lipid-based vehicles for peptide and protein drugs. Part I selection and analysis issues. Biopharm. 1990, 3 (3), 27-32. 

Around 1990, the pulmonary delivery of liposomes was largely an academic exercise [43-46] and at best at an early stage of commercial development [47]. However, these and earlier efforts demonstrated the utility of liposomes, and interest has continued to flourish. This has been reinforced by greater acceptance of the dosage form, since there are now several injectable liposomal products on the market [e.g., Ambisome , Fungisome , Myocet ]. The specific use of lipid-based vehicles to deliver plasmid-based DN A has attracted much attention [48-51]. These developments have indirectly helped improve the quality and variety of... 

Stuchlik M and Zak, S. Lipid-Based Vehicle for Oral Delivery. BiomedPapers 2001 145 17-26. 

A. J. Hutnberslone, W. N. Charman. Lipid-based vehicles for the oral delivery of ponrly water soluble drugs. Adv Drug Deliv Rev 15 103-128. 1997. 

Another approach in using a lipid-based formulation is to micronize the lipid with the dissolved drug to create a microemulsification. This allows an increased surface area available for the dissolution of the drug from the lipid phase. In these mixtures, a surfactant is usually added to improve the ability of oil to accommodate a hydrophobic drug in solution, and the resulting liquid is almost clear. Also a surfactant can function in the GI tract to help disperse the liquid vehicle on dilution. This allows the drug (dissolved in oil droplets/surfactant) to spread readily along the GI tract. 

In conclusion, the recent increase in the number of water-insoluble drug candidates will doubtless enhance the importance of oral lipid-based formulations in the coming years. If a candidate has adequate solubility in the vehicles described in this chapter, lipid-based systems will usually provide an attractive approach for efLcient in-house development of clinical and commercial formulations. 

The ability of lipid vehicles (either in the pharmaceutical formulation or in food) to enhance the absorption of lipophilic drugs has been well known for many years. Recently, successful bioavailability enhancement utilizing lipid-based formulations has been accomplished with the immunosuppressive agent cyclosporine A (Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ), and for the two HIV protease inhibitors ritonavir (Norvir, Abbott Laboratories, IL) and saquinavir (Fortovase, Roche Pharmaceuticals, Nutley, NJ). Consequently, considerable interest in lipid-based formulations has been aroused. 

The class of the lipid in the formulation may also influence the extent and rate of lymphatic absorption of the coadministered drug. Charman and Stella examined the lymphatic transport of DDT following oral administration in different lipidic formulations. Cumulative DDT transported via lymph was twofold greater when administered in a FA (oleic acid)-based vehicle in comparison to a TG-based formulation. In addition, a faster appearance of the DDT in the lymph was observed with the FA formulation [87]. 

A systematic view on the topic of complexation and complexes in the literature shows a great number of important research results. This expanding field covers studies of various systems, including antibody-antigen complexes, proteinase-inhibitor complexes, lipid-based delivery vehicles, metal complexes with DNA base pair, and aqua ligand in the coordination sphere of metal, The metal-modified structures are dominated by these metal-base interactions. However, the structural role of the water molecules in the complexes is quite apparent, as suggested by crystallographic studies.f ... 

Lipid-based formulations of poorly water soluble drugs offer large versatility for oral administration as they can be formulated as solutions, gels, suspensions, emulsions, self-emulsifying systems, multiple emulsions, microemulsions, liposomes, and solid dispersions. " Administration of a drug in a lipidic vehicle/formu-lation can enhance the absorption and oral bioavailability via a combination of various mechanisms " " that are briefly summarized as follows ... 

The micelle-forming molecule TPGS is an effective vehicle for lipid-based drug delivery, and is also a water-soluble source of the water-insoluble oil Vitamin [16] jjjY protease inhibitor, amprenavir,... 

Lipid-based carriers have been established to transport DNA into cells, but the efficiency of protein delivery based on conventional liposomal formulations is below 5%. Zelphati et al., however, have developed a new lipid formulation that interacts rapidly and noncovalently with protein, creating a protective vehicle for delivery.56 The protein encapsulated in the formulation binds to the negatively charged membrane, is internalized in endosomal vesicles by endocytosis, and is then released inside the cell. The system displays no significant toxicity under optimal conditions. 

The lipid-based DNA delivery system was first used on the premise that naked DNA on injection in vivo might be degraded by endogenous DNAase. The lipidic delivery vehicle would provide protection to the DNA during circulation through the blood stream, and with necessary chemical modification, this vehicle would confer targeting potential to the DNA towards specific cellular sites. 

Meilander, N.J. et al., Lipid-based microtubular drug delivery vehicles, Journal of Controlled Release, 2002, 71, 141-152. 

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