LIPID BASED PARENTERAL DRUG DELIVERY SYSTEM
HTML Full TextLIPID BASED PARENTERAL DRUG DELIVERY SYSTEM
Shery Jacob
College of Pharmacy, Gulf Medical University, Ajman, UAE
ABSTRACT
Lipid-based drug delivery systems in the form of triglyceride emulsions, micellar systems and liposomes have been used for parenteral administration for the last few decades. Large number of new chemical entities (NCE) presents formulation and bioavailability problems because of the dose and poor solubility in solvent and co-solvent systems. In addition, high drug concentrations can lead to irritation and pain at the site of injection. There is an increasing interest to expand the range of targetable lipid based systems to solubilize a wide variety of drugs, to improve stability, ease of processing and manufacture in a sterile form. New class of parenteral lipid based drug delivery system includes Tocol emulsions, solid lipid nanoparticles and nanosuspensions, sterically stabilized phospholipid micelles, lipid micro-bubbles and lipoprotein drug carriers. This review article covers the challenges faced by the formulation scientist at each stage of product development of lipid based drug delivery system.
Keywords:
Lipid based delivery system, Tocol emulsions, Polymeric micelle, Solid lipid nanoparticles, Microbubbles, |
Lipoproteins
INTRODUCTION 1-14:In the past, surfactant systems as well as phospholipids emulsified triglyceride emulsions have been used as drug carriers for parenteral nutrition. Since many drugs are hydrophobic, they are sufficiently soluble in vegetable oils to enable the formulations like drug-loaded emulsions e.g. the intravenous anaesthetic Propofol. Lipid based drug delivery system are described under following titles like tocol emulsions, solid lipid nanoparticles and nanosuspensions, sterically stabilized phospholipid micelles, lipid microbubbles and lipoprotein drug carriers respectively.
Tocols: Tocols represent a family of tocopherols, tocotrienols, and their derivatives. They are fundamentally derived from the simplest tocopherol, 6-hydroxy-2-methyl-2-phytylchroman, which is also referred as ‘‘tocol’’. The most common tocol is D-α-tocopherol, also known as vitamin E.
Tocols can be an excellent solvents for water insoluble drugs and are compatible with other cosolvents, oils and surfactants, ‘‘solubility in vitamin E’’ parameter (SVE) to predict solubility of a drug in vitamin E.
SVE can be defined as the solubility in chloroform divided by the solubility in methanol, expressed in mg/ml. An SVE of greater than 10, preferably greater than 100, would indicate solubility in vitamin E. Many tocol emulsions have been developed like Paclitaxel emulsion, an antineoplastic drug 1.
In conventional injectable formulations, non-aqueous solvents, such as ethanol, and solubilizers, such as Cremophor, Tween 80 are often added to enable adequate solubilization of highly hydrophobic drugs. Certain practical considerations and guidelines for the solubility studies of tocol emulsions have been proposed by Illum et al and given in Table 1 2, 3.
TABLE 1: SOLUBILITY OF DRUGS IN ORGANIC SOLVENTS AND VITAMIN E
Drug | Solubility (mg/ml) | Parameter | ||||
Water | Methanol | Chloroform | Vitamin E | SVE | Solubility | |
Itraconazole | Insoluble | Insoluble | 500 | 60 | >1000 | 10.6 |
Paclitaxel | Insoluble | 0.03 | 6 | 11 | 200 | 11.9 |
Cyclosporine | Slightly soluble | 0.71 | 313 | 100 | 520 | 10.7 |
Ergosterol | Insoluble | 1.5 | 32 | 50 | 25 | 9.6 |
Cholesterol | 0.22 | 5 | 200 | 150 | 40 | 9.6 |
Prednisolone | Insoluble | 33 | 5 | Insoluble | 0.02 | 13.6 |
Manufacturing and packaging conditions are necessary due to the ability of these components to leach undesirable substances like plasticizers from intra-venous infusion tubing and bottles. Recent advances in the use of α-tocopherol or other tocopherols, tocotrienols or derivatives as a solvent to dissolve water insoluble drugs have been described in current literature 4-5.
The drugs that have shown increased solubility in tocol emulsions include cyclosporine, paclitaxel, few steroids and antibiotics. These recent advancement have expanded the application of tocopherols and tocotrienols as a solvent for delivery of hydrophobic drugs, particularly when combined with d-alpha tocopheryl polyethylene-glycol succinate (TPGS), phospholipids, and certain co-solvents and emulsifiers. In addition, vitamin E, tocopherol esters including TPGS, were recently found to be useful in pharmaceutical formulations as solubilizers and cosolvents for the administration of medicaments 6-7.
The potential disadvantages of tocol based emulsions may include: drug solubility limitations; requirement of biocompatible surfactants for formulation and stability; limited methods for sterilization; and intolerance of tocopherol in chronic administration.
Marketed Formulations: Taxol® is the first marketed formulation containing paclitaxel approved by the FDA in 1992. It is formulated in a mixture of polyoxy-ethylated castor oil and ethyl alcohol. Cremophor EL has been associated with a wide range of toxicities, including bronchospasm, hypotension, and other hypersensitivity-type reactions 8, 9.
TOCOSOL™ paclitaxel tocol emulsion is currently in advanced clinical development. It offers several advantages over the existing Cremophor: ethanol formulation, including a ready-to use product that incorporates high drug loading of paclitaxel (10 mg/ml), smaller dose, and shorter infusion periods.
The commercially available product, Cordarone® IV is currently formulated in a vehicle containing a 10% (w/v) polysorbate 80 and 2% (w/v) benzyl alcohol. The first parenteral fat emulsion i.e., Intralipid was developed for parenteral nutrition in 1960's. A major disadvantage is the critical physical stability of the emulsions due to a reduction of the zeta potential (ZP) which can lead to agglomeration, drug loss and breaking of the emulsion 10.
Solid Lipid Nanoparticles: SLN are particles made from solid lipids stabilized by surfactant. The lipids can be highly purified triglycerides, complex glyceride mixtures or even waxes. The main advantages of SLN are the better physical stability, protection from degradation, controlled and sustained drug release, good tolerability and site specific targeting. Potential disadvantages include insufficient loading capacity, drug loss after polymorphic transition during storage and high water content of the dispersions (80-99%).
Solid lipid nanoparticles (SLN) formulations by various routes of administration have been developed and characterized both in vitro and in vivo 11-15.
Nano lipid carrier (NLN) have been introduced in late 1990s in order to overcome the potential problems of SLN described above 16, 17.
The development of a nanoparticulate lipid carrier with nanostructure could increase the payload and prevent drug expulsion. This could be realized in three ways. In the first model, spatially different lipids composed of different fatty acids are mixed. This leads to larger distances between the fatty acid chains of the glycerides and imperfections in the crystal. Thus there is more room for the accommodation of guest molecules. In ‘‘imperfect type NLC’’ the highest drug load could be achieved by mixing solid lipids with small amounts of liquid lipids. In LDC nanoparticles, high drug loading capacities of up to 40% have been developed at the turn of the millennium 18, 19.
Here, an insoluble drug–lipid conjugate bulk is prepared either by salt formation or by covalent linking which could be firmly incorporated in the solid lipid matrix 20-21. Hot pressure homogenization (HPH) is a suitable method for the preparation of SLN, NLC and LDC and can be performed at elevated or below room temperature 22-23.
The particle size is decreased by cavitation and turbulences. Different methods have been used for the production of SLN like precipitation, solvent emulsification-evaporation, and spray congealing method.
The physical stability of SLN dispersions has been investigated intensively by various particle size analyzing techniques like Photon Correlation Spectroscopy, Laser Diffraction, Thermal Analysis by Differential Scanning Calorimetry and surface charge by zeta potentiometer. The influence of lipid and carbohydrate types and its concentration, redispersion and spraying medium have been investigated by Freitas and coworkers 24.
SLN may be injected intravenously due to smaller particle size and can be used for targeted drug delivery to specific organs. These particles are cleared from the circulation by the reticuloendothelial system of liver and spleen. Reticuloendothelial system stealth facility was also used for tumor targeting using poly-oxyethylene functional groups. Few examples of drugs meant for parenteral application incorporated into SLN are given in Table 2.
TABLE 2: DRUGS INCORPORATED INTO SLN FOR PARENTERAL APPLICATION
Drugs | References |
AZT-P& derivatives, Camptothecin | 25, 26, 27 |
Camptothecin | 28 |
Clobetasol propionate | 29 |
Cyclosporine-A | 30 |
Mifepristine | 31 |
Paclitaxel | 32, 33 |
Tobramycin | 34 |
Thymopentin | 35 |
Polymeric Micelle: The use of micelles prepared from amphiphilic copolymers combining hydrophilic and hydrophobic characteristics for solubilization of poorly soluble drugs has attracted much attention recently 36-38. If the drug target is located inside the cell, it must have a certain degree of hydrophobicity in order to cross the cell membrane 39-40.
Polymeric micelles are particles with diameters typically smaller than 100 nm formed by amphiphilic polymers dispersed in aqueous media. Within the structure of an amphiphilic polymer, monomer units with different hydrophobicity can be combined randomly, represented by two conjugated blocks each consisting of monomers of the same, or be made from alternating blocks with different hydrophobicity.
Alternatively, the hydrophilic backbone chain of a polymer can be grafted with hydrophobic blocks. Polymeric micelles solubilize poorly water-soluble drugs by incorporating them into their hydrophobic core thus allowing for an increased bioavailability. The use of polymeric micelles often allows for high physical stability, extended circulation time, significant bio-distribution and lower toxicity of a drug. In some cases, targeting is achieved through the enhanced permeability and retention (EPR) effect 41.
The most convenient and simplified technique for the preparation of drug-loaded PEG–PE micelles involves simple dispersing a dry PEG–PE–drug mixture in an aqueous buffer. Solutions of PEG–PE and a drug of interest in miscible volatile organic solvents are mixed, and organic solvents are evaporated to form a PEG–PE–drug film. The film obtained is then hydrated in the presence of an aqueous buffer and the micelles are formed by intensive shaking.
The targeted drug-delivery system using polymeric micelles could be further enhanced by attaching ligands to the micelle surface, which include antibodies against specific receptors in tissues and organs 42-45. The antibody was attached to the micellar surface using a procedure recently developed for the attachment of specific ligands to liposomes 46-47. One of the polymers that have gained popularity as a hydrophilic polymer component of drug-delivery systems is highly biocompatible polyvinyl alcohol (PVP) 37.
PVP was used in formulations of such particulate drug carriers as liposomes 49, nanoparticles 50, microsphere 51 and diblock polymer micelles 52, 53. These micelles can be loaded with a variety of hydrophobic drugs, and are very stable both in terms of the ability to retain their morphology and encapsulated material upon conditions modeling parenteral administration.
The attachment of anticancer antibody to the micelle surface (immunomicelles) could further enhance tumor targeting. Anticancer drugs encapsulated into micelles prepared from polymer-lipid conjugates demonstrate an increased antitumor efficiency in vitro and in vivo compared to free drugs. Pharmaceutical polymer-lipid conjugate-based micelles and immuno-micelles can be used for the solubilization and enhanced delivery of poorly soluble drugs to tumors.
Microbubbles: Microbubbles are comprised of spherical voids or cavities filled by a gas and stabilized by coating materials such as phospholipid, surfactant, denatured human serum albumin or synthetic polymer. Since gas is less dense than liquids or solids, microbubbles have a number of potentially important medical applications like site-specific delivery, treatment of thrombosis and pulmonary delivery. One way of exploiting the diagnostic and therapeutic applications of microbubbles is with ultrasound.
In order to use microbubbles for intravascular applications, they must be smaller than erythrocytes. The microbubbles must be sufficiently stable, that after injection into the blood, they will circulate for a long enough period of time to reach the target site. Significant applications of lipid coated microbubbles are given in Table 3.
TABLE 3: IMPORTANT APPLICATIONS OF LIPID-COATED MICROBUBBLES
Application | Notes | References |
Therapeutic imaging | Microbubbles enable visualization of blood flow. | 54-58 |
Sonothrombolysis | Microbubbles accelerate clot lysis with ultrasound. | 59-64 |
Drug delivery to brain | Transcranial application of therapeutic ultrasound with IV delivery of bubbles leads to reversible opening of blood–brain barrier potential to deliver macromolecules and low molecular weight therapeutics to CNS. | 65-67 |
Gene delivery | Co-administration of microbubbles with plasmid DNA, antisense oligonucleotides, or other gene medicines. | 68, 69 |
Targeted microbubbles | Incorporation of ligands onto surface of microbubbles enables targeting to cell-specific receptors. | 70 |
Perflourocarbon nanoemulsions | Sub-micron-sized particles using liquid PFCs have enhanced fusogenic properties for gene and drug delivery. | 71-73 |
Pulmonary delivery oxygen delivery | Low-density drug carrying microbubbles have good properties for delivery of materials deep into lung. | 74 |
Marketed Formulations: An IV injectable ultrasound contrast agent, Perflutren (phospholipid- coated perfluoropropane filled microbubbles), is approved by the US FDA. In the US, "Definity" is approved for echocardiography and in Canada for both radiology and cardiology indications. The phospholipid coating in Definity is designed to stabilize bubbles of defined size. The lipid coating in Definity is composed of three different phospholipids, Dipalmitoylphosphatidyl choline (DPPC), Dipalmitoylphosphatidic acid (DPPA), and dipalmitolyphosphatidylethanolamine–PEG5000 (DPPE–PEG5000).
Lipoproteins: Lipoproteins are a class of complex macromolecules consisting of both lipid and protein subgroups. Its responsibility is to transport a number of hydrophobic nutrients throughout the systemic circulation, mainly lipids in an aqueous environment. They are characterized by an insoluble core made of cholesteryl ester-triglyceride surrounded by a shell of amphipathic phospholipids and specialized proteins called apolipoproteins 75-76.
Plasma lipoproteins are primarily involved in the transport of lipids and proteins throughout systemic circulation. Lipoprotein’s biological significance extends beyond transport of lipids and hydrophobic drugs.
Drugs such as halofantrine (Hf) amphotericin B (AmpB) and cyclosporine A (CsA) are specifically bound with lipoproteins. By understanding the mechanism of action of these lipoprotein bound drugs, which is taken up intracellularly may provide novel methods in drug targeting. There have been a number of studies suggesting that the LDL receptor and members of its super-family may be playing a role in cellular drug uptake, specifically, aminoglycosides, type-I ribosome-inactivating proteins (RIP), anionic liposomes and cyclosporine Administration of drugs such as CsA, Hf and amphotericin B lipid complex usually results in abnormal lipid levels secondary to the disease state.
Therefore, by understanding the mechanisms in which lipoproteins can bind to hydrophobic drugs, it can predict their therapeutic effects and/or their toxicities leading to improved administration and patient treatment of these drugs. An enhanced antiproliferative effect of CsA was observed when the drug was bound to LDL but was not evident when the drug was bound to either VLDL or HDL 77-78.
In addition, modification of the lipoprotein surface charge with an increased negative charge resulted in greater percentage of CsA recovered within the LDL subfraction after incubation in phosphatidylinositol treated rabbit plasma than control plasma79. Halofantrine is a therapeutic agent used in the effective treatment of malaria, particularly against Plasmodium falciparum and other multi-resistant strains 80-81.
The distribution of Hf between plasma lipoproteins is highly correlated with 0a0 polar core lipid of individual plasma lipoprotein fractions and binding of the Hf enantiomers to different plasma lipoprotein subclasses is stereoselective and species specific 82-83.
Taken together, these studies suggest that the bioavailability and clearance of Hf could be affected by its association to lipids 84. Plasma distribution of free and liposomal nystatin in human plasma of various lipoprotein compositions revealed a majority of these formulations recovered in the HDL fraction. This preferential distribution of nystatin may be a function of the protein composition of the HDL particle 85-86.
Thus, lipoproteins can act as a natural drug delivery system for hydrophobic drugs or lipid-based formulations. By understanding the uptake mechanisms of these specific drug delivery systems, it can provide better therapeutic treatments and administration to patients who experience side effects or low efficacy.
CONCLUSION: Novel nanoparticulate carrier systems based on lipids could make an important impact on clinical practice for critical drugs such as in cancer chemotherapy, for diagnostic agents, DNA, and vaccines. In light of their physical chemical diversity and biocompatibility, lipid formulations are attractive candidates for improving drug solubility and for targeting specific tissues.
REFERENCES:
- Constantinides PP, Lambert KJ, Tustian AK and Nienstedt AM: Compositions of tocol-soluble therapeutics. US Patent No. 6,479,540; 2002.
- Illum L, Washington C, Lawrence S and Watts P: Lipid vehicle drug delivery composition containing vitamin E. WO 97/ 03651 Patent; 1997.
- Han J. The Formulation and Evaluation of Intravenous Vitamin E Emulsions for the Delivery of Paclitaxel, Ph.D Thesis, University of Nottingham; 2000.
- Nielsen B. Tocopherol as an Oral Drug Delivery System. Ph. D Thesis, The Royal Danish School of Pharmacy; 2000.
- Davis SS, Han J. TaxolR emulsion. WO 99/04787; 1999.
- Lambert KJ, Constantinides PP and Quay SC: Emulsion vehicle for poorly soluble drugs. US Patent No. 6,458,373; 2002.
- Constantinides P, Lambert KJ, Tustian AK and Nienstedt AM: Compositions of tocol-soluble therapeutics. US Patent No. 6,479,540; 2002.
- Lorenz W, Reimann HJ, Schmal A, Schult H, Lang S and Ohmann C: Histamine release in dogs by Cremophor EL and its derivatives: oxyethylated oleic acid is the most effective constituent. Agents Actions 1977; 7:63– 67.
- Dye D and Watkins J: Suspected anaphylactic reaction to Cremophor EL: Br Med J 1980; 280: 1353-1360.
- Collins-Gold L, Feichtinger N and Wa¨rnheim T: Are lipid emulsions the drug delivery solution? Mod Drug Discov 2000; 3:44–48.
- Gasco MR: Solid lipid nanoparticles for drug delivery. Pharm Tech Eur 2001: 32–40.
- Cavalli R, Gasco MR, Chetoni P, Burgalassi S and Saettone MF: Solid lipid nanoparticles (SLN) as ocular delivery system for tobramycin. Int J Pharm 2002; 238:241–245.
- Jenning V, Scha¨fer-Korting M and Gohla S: Vitamin A-loaded solid lipid nanoparticles for topical use: drug release properties. J Control Release 2000; 66:115–126.
- Videira MA, Almeida AJ, Botelho MF, Santos AC, Gomes C and Delima JJP: Lymphatic uptake of radiolabelled solid lipid nanoparticles administered by the pulmonary route. Eur J Nucl Med 1999; 26:1168-1174.
- Yang S, Zhu J, Lu Y, Liang B and Yang C: Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharm Res 1999; 16:751–757.
- Mu¨ller RH, Radtke M and Wissing SA: Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm 2002; 242:121–128.
- Radtke M and Mu¨ller RH: Comparison of structural properties of solid lipid nanoparticles (SLNk) versus other lipid particles, Proc Int Symp Control Rel Bioact Mater 2000; 27:309– 310.
- Radtke M and Mu¨ller RH: NLC—nanostructured lipid carriers: the new generation of lipid drug carriers. New Drugs 2001; 2:48– 52.
- Olbrich C, Geßner A, Kayser O and Mu¨ller RH: Lipid– drug conjugate (LDC) nanoparticles as novel carrier system for the hydrophilic antitrypanosomal drug diminazenediaceturate, J Drug Target 2002; 10:387–396.
- Morel S, Gasco MR and Cavalli R: Incorporation in lipospheres of [D-Trp-6] LHRH. Int J Pharm 1994; 105:R1– R3.
- Almeida AJ, Runge S and Mu¨ller RH: Peptide-loaded solid lipid nanoparticles (SLN): influence of production parameters. Int J Pharm 1997; 149:255–265.
- Sjo¨stro¨m B, Kaplun A, Talmon Y and Cabane B: Structure of nanoparticles prepared from oil-in-water emulsions. Pharm Res 1995; 12:39–48.
- Shahgaldian P, Da Silva E, Coleman AW, Rather B and Zaworotko MJ: Para-acyl-calix-arene based solid lipid nanoparticles (SLN): a detailed study of preparation and stability parameters. Int J Pharm 2003; 253:23–38.
- Freitas C and Mu¨ller RH: Spray-drying of solid lipid nanoparticles (SLN). Eur J Pharm Biopharm 1998; 46:145–151.
- Heiati H, Tawashi R, Phillips NC. Drug retention and stability of solid lipid nanoparticles containing azidothymidine palmitate after autoclaving, storage and lyophilization. J Microencapsul 1998; 15:173– 184.
- Heiati H, Tawashi R, Shivers RR, Phillips NC. Solid lipid nanoparticles as drug carriers:I. Incorporation and retention of the lipophilic prodrug 3V-azido-3V-deoxythymidine palmitate, Int J Pharm 1997; 146:123–131.
- Heiati H, Tawashi R, Phillips NC. Solid lipid nanoparticles as drug carriers: II. Plasma stability and biodistribution of solid lipid nanoparticles containing the lipophilic prodrug 3Vazido-3V-deoxythymidine palmitate in mice. Int J Pharm 1998; 174:71– 80.
- Yang SC, Lu LF, Cai Y, Zhu JB, Liang BW, Yang CZ. Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain, J Control Release 1999; 59:299–307.
- Hu FQ, Yuan H, Zhang HH, Fang M. Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization. Int J Pharm 2002; 239:121–128.
- Ugazio E, Cavalli R, Gasco MR. Incorporation of cyclosporine A in solid lipid nanoparticles. Int J Pharm 2002; 241:341– 344.
- Hou DZ, Xie CS, Huang KJ, Zhu CH. The production and characteristics of solid lipid nanoparticles. Biomaterials 2003; 24:1781–1785.
- Chen DB, Yang TZ, Lu WL, Zhang Q. In vitro and in vivo study of two types of long-circulating solid lipid nanoparticles containing paclitaxel. Chem Pharm Bull 2001; 49:1444–1447.
- Cavalli R, Caputo O, Gasco MR: Preparation and characterization of solid lipid nanospheres containing paclitaxel, Eur J Pharm Sci 2000; 10:305–309.
- Bargoni A, Cavalli R, Zara GP, Fundaro A, Caputo O, Gasco MR. Transmucosal transport of tobramycin incorporated in solid lipid nanoparticles (SLN) after duodenal administration to rats: Part II. Tissue distribution. Pharm Res 2001; 43:497–502.
- Morel S, Ugazio E, Cavalli R, Gasco MR. Thymopentin in solid lipid nanoparticles. Int J Pharm 1996; 132:259–261.
- Kwon GS and Kataoka K: Block copolymer micelles as long circulating drug vehicles. Adv Drug Deliv Rev 1995; 16:295–309.
- Jones M and Leroux J: Polymeric micelles—a new generation of colloidal drug carriers. Eur J Pharm Biopharm 1999; 48:101–111.
- Torchilin VP: Structure and design of polymeric surfactant based drug delivery systems. J Control Release 2001; 73:137–172.
- Yokogawa K, Nakashima E, Ishizaki J, Maeda H, Nagano T and Ichimura F: Relationships in the structure – tissue distribution of basic drugs in the rabbit. Pharm Res 1990; 7:691–696.
- Hageluken A, Grunbaum L, Nurnberg B, Harhammer R, Schunack W and Seifert R: Lipophilic beta-adrenoceptor antagonists and local anesthetics are effective direct activators of G-proteins. Biochem Pharmacol 1994; 47:1789–1795.
- Maeda H, Wu J, Sawa T, Matsumura Y and Hori K: Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 2000; 65:271– 284.
- Torchilin VP, Lukyanov AN, Gao Z and Papahadjopoulos- Sternberg B: Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs. Proc Natl Acad Sci USA 2003; 100:6039– 6044.
- Kabanov AV, Chekhonin VP, Alakhov V, Batrakova EV, Lebedev AS and Melik-Nubarov NS: The neuroleptic activity of haloperidol increases after its solubilization in surfactant micelles. Micelles as micro-containers for drug targeting, FEBS Lett. 1989; 258:343– 345.
- Yokoyama M, Okano T, Sakurai Y, Kataoka K and Inoue S: Stabilization of disulfide linkage in drug– polymer–immunoglobulin conjugate by microenvironmental control. Biochem Biophys Res Commun 1989; 164:1234–1239.
- Vinogradov S, Batrakova E, Li S and Kabanov A: Polyion complex micelles with protein-modified corona for receptor mediated delivery of oligonucleotides into cells. Bioconjug Chem 1999; 10:851–860.
- Torchilin VP, Levchenko TS, Lukyanov AN, Khaw BA, Klibanov AL and Rammohan R: P-Nitrophenylcarbonyl –PEG–PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups. Biochim Biophys Acta 2001; 1511:397– 411.
- Torchilin VP, Rammohan R, Weissig V and Levchenko TS: TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors. Proc Natl Acad Sci USA 2001; 98:8786–8791.
- Johnson SD, Anderson JM and Marchant RE: Biocompatibility studies on plasma polymerized interface materials encompassing both hydrophobic and hydrophilic surfaces. J Biomed Mater Res 1992; 26:915– 935.
- Torchilin VP, Shtilman MI, Trubetskoy VS, Whiteman KR and Milstein AM: Amphiphilic vinyl polymers effectively prolong liposome circulation time in vivo. Biochim Biophys Acta 1994; 1195: 181–184.
- Sharma D, Chelvi TP, Kaur J, Chakravorty K, De TK, Maitra A and Ralhan R. Novel Taxol formulation: polyvinylpyrrolidone nanoparticle-encapsulated Taxol for drug delivery in cancer therapy. Oncol Res 1996; 8:281–286.
- Moneghini M, Voinovich D, Princivalle F and Magarotto L: Formulation and evaluation of vinylpyrrolidone/vinylacetate copolymer microspheres with carbamazepine. Pharm Dev Technol. 2000; 5:347–353.
- Le Garrec D, Taillefer J, Van Lier JE, Lenaerts V and Leroux JC: Optimizing pH-responsive polymeric micelles for drug delivery in a cancer photodynamic therapy model. J Drug Target 2002; 10: 429–437.
- Benahmed A, Ranger M and Leroux JC: Novel polymeric micelles based on the amphiphilic diblock copolymer poly(N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide). PharmRes 2001; 18: 323–328.
- Oshowo A, Gillams AR, Lees WR, Taylor I. Radiofrequency ablation extends the scope of surgery in colorectal liver metastases. Eur J Surg Oncol 2003; 29:244–247.
- Komorizono Y, Oketani M, Sako K, Yamasaki N, Shibatou T, Maeda M. Risk factors for local recurrence of small hepatocellular carcinoma tumors after a single session, single application of percutaneous radiofrequency ablation. Cancer 2003; 97:1253–1262.
- Hohmann J, Albrecht T, Hoffmann CW, Wolf KJ. Ultrasonographic detection of focal liver lesions: increased sensitivity and specificity with microbubble contrast agents. Eur J Radiol 2003; 46: 147– 159.
- Harvey CJ, Kim AK, Blomley MJ, Taylor-Robinson SD, Gedroyc WM, Cosgrove DO. Detection of an occult hepatocellular carcinoma using ultrasound with liver-specific microbubbles. Eur Radiol 2002; 12 Suppl: S70–S73.
- Barr R. ATL/Philips Ultrasound, Seeking consensus: contrast ultrasound in radiology. Eur J Radiol 2002; 41:207–216.
- Birnbaum Y, Luo H, Nagai T, Fishbein MC, Peterson TM, Li S, et al. Noninvasive in vivo clot dissolution without a thrombolytic drug: recanalization of thrombosed iliofemoral arteries by transcutaneous ultrasound combined with intravenous infusion of microbubbles. Circulation 1998; 97: 130– 134.
- V.N. Suchkova VN, R.B. Baggs RB, C.W. Francis CW. Effect of 40 kHz ultrasound on acute thrombotic ischemia in a rabbit femoral artery thrombosis model: enhancement of thrombolysis and improvement in capillary muscle perfusion. Circulation 2000; 101:2296–2301.
- Everbach EC, Francis CW. Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz. Ultrasound Med Biol 2000; 26:1153–1160.
- Francis CW. Ultrasound-enhanced thrombolysis. Echocardiography 2001; 18:239– 246.
- Siegel RJ, Atar S, Fishbein MC, Brasch AV, Peterson TM, Nagai T, Noninvasive transcutaneous low frequency ultrasound enhances thrombolysis in peripheral and coronary arteries. Echocardiography 2001; 18:247– 257.
- Dhond MR, Nguyen TT, Dolan C, Pulido G, Bommer WJ. Ultrasound-enhanced thrombolysis at 20 kHz with airfilled and perfluorocarbon-filled contrast biospheres. J Am Soc Echocardiogr 2000; 13: 1025– 1029.
- Hynynen K, McDannold N, Vykhodtseva N, Jolesz F. Noninvasive MR imaging-guided focal opening of the blood – brain barrier in rabbits. Radiology 2001; 220:640–646.
- Mesiwala AH, Mourad PD. Monitoring of biologic effects of focused ultrasound beams on the brain. Radiology 2002; 224:294–296.
- Mesiwala AH, Farrell L, Wenzel HJ, Silbergeld DL, Crum LA, Winn HR, Mourad PD. High-intensity focused ultrasound selectively disrupts the blood – brain barrier in vivo. Ultrasound Med Biol 2002; 28:389–400.
- Unger EC, Hersh E, Vannan M, Matsunaga TO, McCreery T. Local drug and gene delivery through microbubbles. Prog Cardiovasc Dis 2001; 44:45–54.
- Miura S, Tachibana K, Okamoto T, Saku K. In vitro transfer of antisense oligodeoxynucleotides into coronary endothelial cells by ultrasound. Biochem Biophys Res Commun 2002; 298:587–590.
- Wu Y, Unger EC, McCreery TP, Sweitzer RH, Shen D, Wu G. Binding and lysing of blood clots using MRX-408, Invest. Radiol 1998; 33:880–885.
- Weiss DJ, Strandjord TP, Liggitt D, Clark JG, Perflubron enhances adenovirus-mediated gene expression in lungs of transgenic mice with chronic alveolar filling. Hum Gene Ther 1999; 10:2287– 2293.
- Weiss DJ, Baskin GB, Shean MK, Blanchard JL, Kolls JK. Use of perflubron to enhance lung gene expression: safety and initial efficacy studies in non-human primates. Molec Ther 2002; 5:8–15.
- Unger EC, McCreery TP, Sweitzer RH, Caldwell VE, Wu Y. Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent. Invest Radiol 1998; 12:886– 892.
- Unger EC. Novel prodrugs compromising fluorinated amphiphiles. US Patent No. 6,028,066; 2000.
- McIntosh MP, Porter CJH, Wasan KM, Ramaswamy M and Charman WN: The degree of association of halofantrine with pre- and post-prandial plasma lipoproteins is determined by their apolar lipid content. Pharm Res 1997; 14: S-277.
- Shephard J and Fruchart JC: Lipoproteins in health and disease:lipoprotein nomenclature and the classification of hyperlipoproteinemia. In: Fruchart JC, Shepard J, editors. Human Plasma Lipoproteins, Clinical Biochemistry: Principles, Methods, Application. vol. 3. Walter de Gruyter: Berlin; 1989. p. 1 – 22.
- Lemaire M, Pardridge WM and Chaudhuri G: Influence of blood components on the tissue uptake indices of cyclosporine in rats. J Pharmacol Exp Ther 1988; 244:740–743.
- Pardridge WM: Carrier-mediated transport of thyroid hormones through the rat blood– brain barrier: primary role of albumin-bound hormone. Endocrinology 1979; 105:605– 612.
- Wasan KM and Sivak O: Modifications in lipoprotein surface charge alter cyclosporine A association with low-density lipoproteins. Pharm Res 2003; 20:126–129.
- Boudreau EF, Pang LW, Dixon KE, Webster HK, Pavanand K, and Tosingha L: Malaria: treatment efficacy of halofantrine (WR 171, 699) in initial trials in Thailand. Bull WHO 1988; 66:227–235.
- Watkins WM, Lury JD, Kariuki D, Koech DK, Oloo JA and Mosoba M:Efficacy of multiple does-halofantrine in the treatment of chloroquine resistant faciparum malaria in Kenya. Lancet1988; ii: 247–250.
- McIntosh MP, Porter CJ, Wasan KM, Ramaswamy M and Charman WN: Differences in the lipoprotein binding profile of halofantrine in fed and fasted human or beagle plasma are dictated by the respective masses of core apolare lipoprotein lipid. J Pharm Sci 1999; 88:378–384.
- Brocks DR, Ramaswamy M, MacInnes AI and Wasan KM: The stereoselective distribution of halofantrine enantiomers within human, dog, and rat plasma lipoproteins. Pharm Res 2000; 17:427–431.
- Brocks DR and Wasan KM: The influence of lipid on stereo selective pharmacokinetics of halofantrine: important implications in food-effect studies involving drugs that bind to lipoproteins. J Pharm Sci 2002; 91:1817–1826.
- Cassidy SM, Strobel FW andWasan KM: Plasma lipoprotein distribution of liposomal nystatin is influenced by protein content of high-density lipoproteins. Antimicrob Agents Chemother 1998; 42:1878– 1888.
- Wasan KM, Ramaswamy M, Cassidy SM, Kazemi M, Strobel FW and Thies RL: Physical characteristics and lipoprotein distribution of liposomal nystatin in human plasma. Antimicrob Agents Chemother 1997; 41:1871–1875.
How to cite this article:
Jacob S:Lipid Based Parenteral Drug Delivery System. Int J Pharm Sci Res, 2012; Vol. 3(9): 2880-2887.