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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Lipid-based colloidal carriers for peptide and protein delivery – liposomes versus lipid nanoparticles

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          Abstract

          This paper highlights the importance of lipid-based colloidal carriers and their pharmaceutical implications in the delivery of peptides and proteins for oral and parenteral administration. There are several examples of biomacromolecules used nowadays in the therapeutics, which are promising candidates to be delivered by means of liposomes and lipid nanoparticles, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). Several production procedures can be applied to achieve a high association efficiency between the bioactives and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. Generally, this can lead to improved bioavailability, or in case of oral administration a more consistent temporal profile of absorption from the gastrointestinal tract. Advantages and drawbacks of such colloidal carriers are also pointed out. This article describes strategies used for formulation of peptides and proteins, methods used for assessment of association efficiency and practical considerations regarding the toxicological concerns.

          Most cited references164

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          Nanostructured lipid matrices for improved microencapsulation of drugs.

          At the beginning of the nineties solid lipid nanoparticles (SLN) have been introduced as a novel nanoparticulate delivery system produced from solid lipids. Potential problems associated with SLN such as limited drug loading capacity, adjustment of drug release profile and potential drug expulsion during storage are avoided or minimised by the new generation, the nanostructured lipid carriers (NLC). NLC are produced by mixing solid lipids with spatially incompatible lipids leading to special structures of the lipid matrix, i.e. three types of NLC: (I) the imperfect structured type, (II) the structureless type and (III) the multiple type. A special preparation process-applicable to NLC but also SLN-allows the production of highly concentrated particle dispersions (>30-95%). Potential applications as drug delivery system are described.
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            Solid lipid nanoparticles: production, characterization and applications.

            W Mehnert (2001)
            Solid lipid nanoparticles (SLN) have attracted increasing attention during recent years. This paper presents an overview about the selection of the ingredients, different ways of SLN production and SLN applications. Aspects of SLN stability and possibilities of SLN stabilization by lyophilization and spray drying are discussed. Special attention is paid to the relation between drug incorporation and the complexity of SLN dispersions, which includes the presence of alternative colloidal structures (liposomes, micelles, drug nanosuspensions, mixed micelles, liquid crystals) and the physical state of the lipid (supercooled melts, different lipid modifications). Appropriate analytical methods are needed for the characterization of SLN. The use of several analytical techniques is a necessity. Alternative structures and dynamic phenomena on the molecular level have to be considered. Aspects of SLN administration and the in vivo fate of the carrier are discussed.
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              Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes.

              In preclinical studies, a doxorubicin liposome formulation containing polyethylene-glycol (Doxil) shows a long circulation time in plasma, enhanced accumulation in murine tumors, and a superior therapeutic activity over free (unencapsulated) doxorubicin (DOX). The purpose of this study was to characterize the pharmacokinetics of Doxil in cancer patients in comparison with free DOX and examine its accumulation in malignant effusions. The pharmacokinetics of doxorubicin and/or liposome-associated doxorubicin were analyzed in seven patients after injections of equivalent doses of free DOX and Doxil and in an additional group of nine patients after injection of Doxil only. Two dose levels were examined, 25 and 50 mg/m2. When possible, drug levels were also measured in malignant effusions. The plasma elimination of Doxil followed a biexponential curve with half-lives of 2 and 45 h (median values), most of the dose being cleared from plasma under the longer half-life. Nearly 100% of the drug detected in plasma after Doxil injection was in liposome-encapsulated form. A slow plasma clearance (0.1 liter/h for Doxil versus 45 liters/h for free DOX) and a small volume of distribution (4 liters for Doxil versus 254 liters for free DOX) are characteristic of Doxil. Doxorubicin metabolites were detected in the urine of Doxil-treated patients with a pattern similar to that reported for free DOX, although the overall urinary excretion of drug and metabolites was significantly reduced. Doxil treatment resulted in a 4- to 16-fold enhancement of drug levels in malignant effusions, peaking between 3 to 7 days after injection. Stomatitis related to Doxil occurred in 5 of 15 evaluable patients and appears to be the most significant side effect in heavily pretreated patients. The results of this study are consistent with preclinical findings indicating that the pharmacokinetics of doxorubicin are drastically altered using Doxil and follow a pattern dictated by the liposome carrier. The enhanced drug accumulation in malignant effusions is apparently related to liposome longevity in circulation. Further clinical investigation is needed to establish the relevance of these findings with regard to the ability of liposomes to modify the delivery of doxorubicin to solid tumors and its pattern of antitumor activity.
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                Author and article information

                Journal
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                December 2007
                December 2007
                : 2
                : 4
                : 595-607
                Affiliations
                [1 ]Department of Pharmaceutical Technology, Faculty of Pharmacy University of Porto, Porto, Portugal;
                [2 ]Faculty of Health Sciences, Fernando Pessoa University, Porto, Portugal
                Author notes
                Correspondence: Eliana B Souto, Fernando Pessoa University, Faculty of Health Sciences Department of Pharmaceutical Technology, Gab. S3 Rua Carlos da Maia, Nr. 296 P-4200-150 Porto Portugal, Tel + 351 225 074630, Fax ++351-225-074637, Email eliana@ 123456ufp.pl
                Article
                ijn-2-595
                10.2147/IJN.S2.4.595
                2676808
                18203427
                c6a16ba2-0bfb-4be0-8e48-48ffa92f4982
                © 2007 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Review

                Molecular medicine
                sln,oral,liposomes,nanostructured lipid carriers,peptides,solid lipid nanoparticles,proteins,nlc,parenteral

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