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      Using liposomes to target infection and inflammation induced by foreign body injuries or medical implants

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      Expert Opinion on Drug Delivery
      Informa Healthcare

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          Abstract

          Foreign body (FB) injuries occur under many circumstances: at work, when practising a hobby, in car accidents, or in violence-afflicted zones. Owing to the nature of these injuries, they are not restricted to a certain part of the body and may affect several organs simultaneously. In general, an FB will be surgically removed when it is a cause of pain or infection or when jeopardizing a critical biological function. However, in many cases removing the FB is not possible owing to risk of harming adjacent delicate tissue. Furthermore, often when surgically removing the FB, microscopic fragments or debris remain at the site of invasion, becoming a cause of pain and recurring infection and inflammation. FB-related complications can also originate from micro- or nanoparticles released by degradation of medical implants. The use of advanced drug delivery technologies to target the tissue surrounding the FB, or the FB itself, may be of therapeutic benefit. Liposomes, vesicles with an aqueous core entrapped in one or more lipid bilayers, are widely used as drug delivery systems. Previous studies show that nanoliposomes can effectively target infected and inflamed tissue. The working hypothesis of this paper is that nanoliposomes, of specific lipid composition, may be used to target FB under conditions of inflammation.

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          Mediation of biomaterial-cell interactions by adsorbed proteins: a review.

          An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. It is well described that implanted materials are immediately coated with proteins from blood and interstitial fluids, and it is through this adsorbed layer that cells sense foreign surfaces. Hence, it is the adsorbed proteins, rather than the surface itself, to which cells initially respond. Diverse studies using a range of materials have demonstrated the pivotal role of extracellular adhesion proteins--fibronectin and vitronectin in particular--in cell adhesion, morphology, and migration. These events underlie the subsequent responses required for tissue repair, with the nature of cell surface interactions contributing to survival, growth, and differentiation. The pattern in which adhesion proteins and other bioactive molecules adsorb thus elicits cellular reactions specific to the underlying physicochemical properties of the material. Accordingly, in vitro studies generally demonstrate favorable cell responses to charged, hydrophilic surfaces, corresponding to superior adsorption and bioactivity of adhesion proteins. This review illustrates the mediation of cell responses to biomaterials by adsorbed proteins, in the context of osteoblasts and selected materials used in orthopedic implants and bone tissue engineering. It is recognized, however, that the periimplant environment in vivo will differ substantially from the cell-biomaterial interface in vitro. Hence, one of the key issues yet to be resolved is that of the interface composition actually encountered by osteoblasts within the sequence of inflammation and bone regeneration.
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            Lipid-based nanoparticles for nucleic acid delivery.

            Lipid-based colloidal particles have been extensively studied as systemic gene delivery carriers. The topic that we would like to emphasize is the formulation/assembly of lipid-based nanoparticles (NP) with diameter under 100 nm for delivering nucleic acid in vivo. NP are different from cationic lipid-nucleic acid complexes (lipoplexes) and are vesicles composed of lipids and encapsulated nucleic acids with a diameter less than 100 nm. The diameter of the NP is an important attribute to enable NP to overcome the various in vivo barriers for systemic gene delivery such as: the blood components, reticuloendothelial system (RES) uptake, tumor access, extracellular matrix components, and intracellular barriers. The major formulation factors that impact the diameter and encapsulation efficiency of DNA-containing NP include the lipid composition, nucleic acid to lipid ratio and formulation method. The particle assembly step is a critical one to make NP suitable for in vivo gene delivery. NP are often prepared using a dialysis method either from an aqueous-detergent or aqueous-organic solvent mixture. The resulting particles have diameters about 100 nm and nucleic acid encapsulation ratios are >80%. Additional components can then be added to the particle after it is formed. This ordered assembly strategy enables one to optimize the particle physico-chemical attributes to devise a biocompatible particle with increased gene transfer efficacy in vivo. The components included in the sequentially assembled NP include: poly(ethylene glycol) (PEG)-shielding to improve the particle pharmacokinetic behavior, a targeting ligand to facilitate the particle-cell recognition and in some case a bioresponsive lipid or pH-triggered polymer to enhance nucleic acid release and intracellular trafficking. A number of groups have observed that a PEG-shielded NP is a robust and modestly effective system for systemic gene or small interfering RNA (siRNA) delivery.
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              Cellular and molecular dynamics in the foreign body reaction.

              Intracorporally implanted materials, such as medical devices, will provoke the body to initiate an inflammatory reaction. This inflammatory reaction to implanted materials is known as the foreign body reaction (FBR) and is characterized by 3 distinct phases: onset, progression, and resolution. The FBR proceeds in the creation of a dynamic microenvironment that is spatially well organized. The progression of the FBR is regulated by soluble mediators, such as cytokines, chemokines, and matrix metalloproteinases (MMPs), which are produced locally by tissue cells and infiltrated inflammatory cells. These soluble mediators orchestrate the cascade of cellular processes in the microenvironment that accompanies the FBR, consisting of cellular activation, angiogenesis, extravasation, migration, phagocytosis, and, finally, fibrosis. The nature of the FBR requires that the soluble mediators act in a spatial and temporally regulated manner as well. This regulation is well known for several inflammatory processes, but scarce knowledge exists about the intricate relationship between the FBR and the expression of soluble mediators. This review discusses the key processes during the initiation, progression, and resolution phase, with emphasis on the role of soluble mediators. Besides other sites of implantation, we focus on the subcutaneous implantation model.
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                Author and article information

                Journal
                Expert Opinion on Drug Delivery
                Expert Opinion on Drug Delivery
                Informa Healthcare
                1742-5247
                1744-7593
                September 22 2010
                October 2010
                September 22 2010
                October 2010
                : 7
                : 10
                : 1175-1189
                Article
                10.1517/17425247.2010.517519
                20858166
                7e0e7651-cac1-4225-bae1-7ad91e8aa595
                © 2010
                History

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