Formulation of poly(d,l-lactic-co-glycolic acid) microparticles for rapid plasmid DNA delivery

Tinsley-Bown, Anne; Fretwell, R; Dowsett, A. B.; Davis, S.L; Farrar, Graham H.

doi:10.1016/s0168-3659(99)00275-8

Cited by 162 publications

(96 citation statements)

References 22 publications

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“…Indeed, this formulation is very potent in mice (25) and appears to function, at least in part, by facilitating DNA uptake by APCs (9). PLG has been used previously for delivery of small-molecule drugs (17), proteins (21,22), and DNA (8,15,18,27). However, in these cases the delivered cargo was encapsulated inside the particles and, hence, may have functioned in a slow-release depot manner.…”

Section: Discussionmentioning

confidence: 99%

“…However, in these cases the delivered cargo was encapsulated inside the particles and, hence, may have functioned in a slow-release depot manner. In contrast, the present formulation, consisting of surface-adsorbed DNA, has a twofold rationale: (i) adsorption onto preformed PLG particles avoids the harsh emulsion conditions, which are known to affect the integrity of DNA (2,27,29); and (ii) it provides a means of delivery to and rapid release of DNA in APCs.…”

Section: Discussionmentioning

confidence: 99%

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Induction of Potent Immune Responses by Cationic Microparticles with Adsorbed Human Immunodeficiency Virus DNA Vaccines

O’Hagan¹,

Singh²,

Ugozzoli³

et al. 2001

J Virol

172

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The effectiveness of cationic microparticles with adsorbed DNA at inducing immune responses was investigated in mice, guinea pigs, and rhesus macaques. Plasmid DNA vaccines encoding human immunodeficiency virus (HIV) Gag and Env adsorbed onto the surface of cationic poly(lactide-coglycolide) (PLG) microparticles were shown to be substantially more potent than corresponding naked DNA vaccines. In mice immunized with HIV gag DNA, adsorption onto PLG increased CD8 ؉ T-cell and antibody responses by ϳ100-and ϳ1,000-fold, respectively. In guinea pigs immunized with HIV env DNA adsorbed onto PLG, antibody responses showed a more rapid onset and achieved markedly higher enzyme-linked immunosorbent assay and neutralizing titers than in animals immunized with naked DNA. DNA vaccines have been shown to induce immune responses and protective immunity in many animal models of infectious disease (for a review, see reference 11). In mice, such responses can often be achieved with low doses (Ͻ1 g) of naked DNA. However, the immunogenicity of DNA vaccines in larger animals (e.g., guinea pigs, rabbits, and nonhuman primates) has been much lower than that observed in mice, even at higher doses of DNA. In human clinical trials, certain DNA vaccines have been shown to induce immune responses (5,19,30), but multiple immunizations of high doses of DNA were required. Therefore, in order to provide protective efficacy in humans, the potency of DNA vaccines needs to be increased. So far, it appears that DNA vaccines are more effective at priming T-cell responses than antibodies, as exemplified by induction of cytotoxic T lymphocytes (CTL) but no antibodies against malaria circumsporozoite protein in humans (30). Similarly, we show here that in mice, human immunodeficiency virus (HIV) gag DNA primed CD8 ϩ T-cell responses at doses of DNA 10-to 100-fold lower than that required for priming of antibody responses. Therefore, technologies aimed at increasing the potency of DNA vaccines need to be especially effective at boosting humoral responses.The technology described herein, formulation of DNA onto cationic poly(lactide-coglycolide) (PLG) microparticles, has been developed as a means to better target DNA to antigen-presenting cells (APCs). PLG microparticles are an attractive approach for vaccine delivery, since the polymer is biodegradable and biocompatible and has been used to develop several drug delivery systems (21). In addition, PLG microparticles have also been used for a number of years as delivery systems for entrapped vaccine antigens (24). More recently, PLG microparticles have been described as a delivery system for entrapped DNA vaccines (15,18). Nevertheless, recent observations have shown that DNA is damaged during microencapsulation, leading to a significant reduction in supercoiled DNA (2, 29). Moreover, the encapsulation efficiency is often low. Therefore, we developed a novel approach of adsorbing DNA onto the surface of PLG microparticles to avoid the problems associated with microencapsulation of DNA. This approach, ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Induction of Potent Immune Responses by Cationic Microparticles with Adsorbed Human Immunodeficiency Virus DNA Vaccines

O’Hagan¹,

Singh²,

Ugozzoli³

et al. 2001

J Virol

172

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“…The main advantages of microparticles is that they may be administered by injection or intranasally as a dry powder, so that a surgical procedure is not required (Baldwin and Saltzman, 1998;Eliaz and Kost, 2000;Tinsley-Brown et al, 2000), and that they may contain a greater amount of biologically active molecules per unit volume (Langer, 1991;Grassi et al, 2001;Janes et al, 2001a). Various parameters, including particle size and distribution, porosity, pore structure and surface area, are considered to describe the overall performance of polymer microparticles in biomedical applications (Tuncel et al, 1996;Allemann et al, 1998;Yang and Alexandridis, 2000).…”

Section: Definitionmentioning

confidence: 99%

Materials in particulate form for tissue engineering. 1. Basic concepts

Silva

Ducheyne

Reis

2007

J Tissue Eng Regen Med

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For biomedical applications, materials small in size are growing in importance. In an era where 'nano' is the new trend, micro-and nano-materials are in the forefront of developments. Materials in the particulate form aim to designate systems with a reduced size, such as micro-and nanoparticles. These systems can be produced starting from a diversity of materials, of which polymers are the most used. Similarly, a multitude of methods are to produce particulate systems, and both materials and methods are critically reviewed here. Among the varied applications that materials in the particulate form can have, drug delivery systems are probably the most prominent, as these have been in the forefront of interest for biomedical applications. The basic concepts pertaining to drug delivery are summarized, and the role of polymers as drug delivery systems conclude this review. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE R E V I E W A R T I C L E

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“…Naked DNA is rapidly degraded in vivo (20). Therefore, the encapsulation of DNA in biodegradable microparticles is a particularly interesting approach that not only targets the APC but also enhances the amount of functional DNA delivered to these cells (3,21,22).…”

Section: Introductionmentioning

confidence: 99%

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

Jilek¹,

Ulrich²,

Merkle³

et al. 2004

Pharm Res

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Purpose. Biodegradable microparticles prepared from poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) have been shown to be promising carrier systems for vaccine delivery. Here, we have investigated the capacity of different PLA and PLGA microparticle formulations to induce stimulation of human blood monocyte-derived dendritic cells (DCs). Methods. Stimulation of human derived dendritic cells by plain microparticles were compared with microparticles loaded with plasmid DNA or double-stranded salmon DNA either by encapsulation or adsorption to the surface of cationic microparticles. Stimulation of DCs was monitored by the up-regulation of surface maturation markers CD83 and CD86 and the secretion of IL-12 and TNF-␣. Results. Slowly degrading PLA microparticles did not induce any detectable stimulation or activation of DCs. In contrast, fast degrading PLGA microparticles were able to influence DC maturation and cytokine secretion dependent on their surface charge. Anionic PLGA microparticles induced an up-regulation of CD83 and high TNF-␣ secretion, which was further enhanced up to the level of the potent stimulator lipopolysaccharide (LPS) when plasmid DNA was encapsulated. Moreover, the secretion of significant amounts of IL-12 was observed. Cationic PLGA microparticles induced an up-regulation of CD86 and moderate TNF-␣ secretion, but no IL-12 secretion, with no additional effects in the presence of plasmid DNA. Conclusions. The data suggest that the composition and charge of biodegradable DNA-loaded microparticles profoundly influences maturation and cytokine secretion in DCs. Thus, the individual formulation of microparticles used as a vaccine carrier system might considerably influence the profile of the immune response.

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Formulation of poly(d,l-lactic-co-glycolic acid) microparticles for rapid plasmid DNA delivery

Cited by 162 publications

References 22 publications

Induction of Potent Immune Responses by Cationic Microparticles with Adsorbed Human Immunodeficiency Virus DNA Vaccines

Induction of Potent Immune Responses by Cationic Microparticles with Adsorbed Human Immunodeficiency Virus DNA Vaccines

Materials in particulate form for tissue engineering. 1. Basic concepts

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

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