Biocompatibility of implantable synthetic polymeric drug carriers: focus on brain biocompatibility

Fournier, E; Passirani, Catherine; Montero‐Menei, Claudia N.; Benoit, Jean‐Pierre

doi:10.1016/s0142-9612(03)00161-3

Cited by 301 publications

(263 citation statements)

References 138 publications

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“…No evidence of damage was observed on the tissue that surrounds the implanted microparticles indicating that they were well tolerated. Consistent with previous reports, GFAP-positive reactive astrocytes were observed around the needle tract ( Figure 6A) [14,16,24]. This reaction was the same for the 3 groups of animals demonstrating that the astrocytic response is attributed to the mechanical trauma that occurs during surgery and not to the polymer.…”

Section: Histological Effects Of Striatal Gdnf Microparticle Implantasupporting

confidence: 91%

“…First of all, microparticles are prepared with biodegradable polymers that do not require removal once the treatment is finished. Secondly, brain biocompatibility of particles prepared with poly (lactic-co-glycolic) acid (PLGA) polymers has already been well established [13][14][15][16] and therefore the appearance of host immune reaction against injected microparticles is very unlikely. Finally, the drug release profile of PLGA microspheres brings another important advantage.…”

Section: Introductionmentioning

confidence: 99%

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Effective GDNF brain delivery using microspheres—A promising strategy for Parkinson's disease

Garbayo

Montero‐Menei

Ansorena

et al. 2009

Journal of Controlled Release

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133

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Glial cell line-derived neurotrophic factor (GDNF) has shown promise in the treatment of neurodegenerative disorders of basal ganglia origin such us Parkinson's disease (PD). In this study, we investigated the neurorestorative effect of controlled GDNF delivery using biodegradable microspheres in an animal model with partial dopaminergic lesion. Microspheres were loaded with N-glycosylated recombinant GDNF and prepared using the Total Recirculation One-Machine System (TROMS). GDNF-loaded microparticles were unilaterally injected into the rat striatum by stereotaxic surgery two weeks after a unilateral partial 6-OHDA nigrostriatal lesion. Animals were tested for amphetamineinduced rotational asymmetry at different times and were sacrificed two months after microsphere implantation for immunohistochemical analysis. The putative presence of serum IgG antibodies against rat glycosylated GDNF was analyzed for addressing safety issues. The results demonstrated that GDNF-loaded microspheres, improved the rotational behavior induced by amphetamine of the GDNF-treated animals together with an increase in the density of TH positive fibers at the striatal level. The developed GDNF-loaded microparticles proved to be suitable to release biologically active GDNF over up to 5 weeks in vivo. Furthermore, none of the animals developed antibodies against GDNF demonstrating the safety of glycosylated GDNF use.

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Section: Histological Effects Of Striatal Gdnf Microparticle Implantasupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Effective GDNF brain delivery using microspheres—A promising strategy for Parkinson's disease

Garbayo

Montero‐Menei

Ansorena

et al. 2009

Journal of Controlled Release

Self Cite

133

View full text Add to dashboard Cite

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“…Polymers derived from D,L lactic and glycolic acids, poly(lactide-co-glycolide) (PLGA), are biocompatible and biodegradable (Visscher et al, 1985;Fournier et al, 2003), they have been widely employed with this aim in mind. Drug release from these systems is due to drug diffusion through water-filled networks of pores and channels coupled with the bulk erosion of the microspheres by hydrolysis of the polymer's ester bond linkages.…”

Section: Introductionmentioning

confidence: 99%

How to achieve sustained and complete protein release from PLGA-based microparticles?

Giteau

Venier-Julienne

Aubert-Pouëssel

et al. 2008

International Journal of Pharmaceutics

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234

184

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One of the most challenging tasks in the delivery of therapeutic proteins from PLGAbased microparticles is the sustained and complete release of the protein in its native form.The mechanisms responsible for incomplete protein release from these devices are numerous and complex; the beneficial effect of different formulations has often been evaluated in vitro.Strategies employed for overcoming protein destabilization during the release step are reviewed in this paper. Proteins have been protected in the deleterious environment by adding stabilizers to the formulation, or by modifying the protein or the polymer. Alternatively, some strategies have aimed at avoiding the formation of the destabilizing environment. As experimental conditions may influence the results from in vitro release studies, we initially report precautions to avoid adverse effects.

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“…9 However, many of these medical devices fail to produce long term therapeutic effect raising serious concerns over the efficiency of these implants. [10][11][12][13][14][15][16][17] For example, the chemotherapeutic doxorubicin delivering millirods has been reported to lose efficacy 8 days post subcutaneous implantation. 8 .…”

Section: Introductionmentioning

confidence: 99%

“…Many recent evidences have supported that dense avascular fibrotic tissues serve as diffusion barrier for the released drugs to enter into circulation and for blood components and nutrition from the tissue fluid to interact with implanted sensor. 11,[18][19][20] The enormity of this complication is underlined by previous studies which have found that even low molecular weight substances cannot cross the barrier. [21][22][23][24] Therefore, it is generally accepted that, by reducing implant-mediated fibrotic tissue, the life span, function, and efficacy of drug releasing devices, sensors, and tissue engineering scaffolds could be substantially improved.…”

Section: Introductionmentioning

confidence: 99%

Species and Density of Implant Surface Chemistry Affect the Extent of Foreign Body Reactions

et al. 2008

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Implant-associated fibrotic capsule formation presents a major challenge for the development of long term drug release microspheres and implantable sensors. Since material properties have been shown to affect in vitro cellular responses and also to influence short term in vivo tissue responses, we have thus assumed that the type and density of surface chemical groups would affect the degree of tissue responses to microsphere implants. To test this hypothesis, polypropylene particles with different surface densities of -OH and -COOH groups, along with the polypropylene control (-CH 2 groups) were utilized. The influence of functional groups and their surface densities on tissue reactions were analyzed using a mice subcutaneous implantation model. Our comparative studies included determination and correlation of the extents of fibrotic capsule formation, cell infiltration into the particles and recruitment of CD11b+ inflammatory cells for all of the substrates employed. We have observed major differences among microspheres coated with different surface functionalities. Surfaces with -OH surface groups trigger the strongest responses while -COOH rich surfaces prompt the least tissue reactions. However, variation of the surface density of either functional group has a relatively minor influence on the extent of fibrotic tissue reactions. The present results show that surface functionality can be used as a powerful tool to alter implant-associated fibrotic reactions and, potentially, to improve the efficacy and function of drug delivery microspheres, implantable sensors and tissue engineering scaffolds.

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Biocompatibility of implantable synthetic polymeric drug carriers: focus on brain biocompatibility

Cited by 301 publications

References 138 publications

Effective GDNF brain delivery using microspheres—A promising strategy for Parkinson's disease

Effective GDNF brain delivery using microspheres—A promising strategy for Parkinson's disease

How to achieve sustained and complete protein release from PLGA-based microparticles?

Species and Density of Implant Surface Chemistry Affect the Extent of Foreign Body Reactions

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