Lipid-based systems

Solubility enhancement systems lipid-based systems, nanoparticles, surfactants, semisolid formulations... 

Maurer N, Mori A, Palmer L, et al. Lipid-based systems for the intracellular delivery of genetic drugs. Mol Membr Biol 1999 16 129. 

Nonaqueous solvents (e.g., PEG-400 and PG) Self-emulsifying lipid-based systems/microemulsions... 

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. 

Al-Razzak, L. A., L. Dias, D. Kaul, and S. Ghosh. 1997. Lipid based systems for oral delivery Physiological mechanistic and product development perspectives. Paper presented atthe AAPS Annual Meeting, Boston, November 2-6, 1997. 

Faneca H, Cabrita AS, Simoes S et al (2007) Evaluation of the antitumoral effect mediated by IL-12 and HSV-tk genes when delivered by a novel lipid-based system. Biochim Biophys Acta-Biomembranes 1768 1093-1102... 

Polymer. The field of nonviral gene delivery using cationic polymers is at its early stage compared to that of cationic lipid. However, this system is also known to have advantages over lipid-based systems in controlling the size, charge, and other physicochemical properties. Polycation-DNA complexes, also called as polyplexes, are formed by a cooperative... 

Transfection efficiency is dependent on mitotic activity, as cells prevented from going into mitosis after transfection express transgenes much less efficiently than proliferating cells. In search for an explanation, the transport of plasmids across the nuclear membranes has been studied. Plasmids injected into the cytoplasm of quiescent human fibroblasts are not expressed, in contrast to plasmid injected into the nucleus. This has been found to be true for the cationic lipid-based systems as plasmid injected into the cytoplasm of Xenopus oocytes is not expressed, unlike that injected into the nucleus, it must be concluded that the plasmid must dissociate from the cationic lipids before entering into the nucleus. 

There has been a number of examples of cylindrical (tubular) supramolecular structures reported over recent years. These encompass all-carbon structures as well as other inorganic and organic tubes (and columns) and include lipid-based systems. However, the majority of these tubes represent extended arrays (on a multi-nanometre or higher scale) and hence fall outside the scope of the present discussion - in any case, many were not obtained directly by self-assembly processes. Indeed, only a limited number of self-assembled, discrete cylindrical systems have been described. 

Non-aqueous solvents and their mixtures Go-solvents Co-solvents, lipid based systems in soft or hard gelatin capsules... 

Surfactants and phospholipid in aqueous and non-aqueous media Micellar solubilization Lipid based systems in Liposome capsules... 

This principle of anhydrous concentrates was named SMEDDS , self micro-emulsifying dmg delivery systems. Such formulations lack the aqueous phase. On dilution, a SMEDDS spontaneously converts to an optically clear, thermodynamically stable microemulsion, which contains the dmg in molecular dispersion. The same principle of a water-free concentrate which leads to a macro -emulsion is called SEDDS, a self-emulsifying dmg delivery system. A recent review on self-dispersing lipid based systems was... 

Deshpande, D., Blezinger, P, Pillai, R., Duguid, J., Freimark, B., and Rolland, A. 1998. Target specific optimization of cationic lipid-based systems for pulmonary gene therapy. Pharmaceutical Research 15 1340-1347. 

Lipid-based systems can achieve sustained release by providing a barrier to diffusion of water, necessary for dissolution of solid protein dispersed in a hydrophobic matrix, and by a subsequent barrier to diffusion or convection of protein solution entrapped within the matrix. The rate-limiting step for aqueous solute release is often dissolution or disintegration of the lipid mass or particle. Factors affecting release of proteins from various matrices have been reviewed in detail by Pitt (1990a) and Park et a/.(1993). 

In the following, lipid-based systems for oral drug delivery of peptides and proteins have been classified into liposomes and emulsions, although the distinction between these classifications is somewhat vague. 

Solubility parameters for many common compounds can be found in the literature [16,18,19], and it has been further demonstrated that the solubility parameters for a given compound can be reasonably estimated on the basis of group contributions and a knowledge of the structure of the molecule [20,21]. Adopting this approach for lipid-based systems has proved to be very successful not only in forecasting vapor-liquid equilibrium data but also for selecting the solvent in liquid-liquid extraction [22] and for solid-liquid equilibrium in fractionation. 

Tseng YC, Mozumdar S, Huang L (2009) Lipid-based systemic delivery of siRNA. Adv Drug Deliv Rev 61 721-731... 

Lipid based system are many used because... 

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