Biodegradable microspheres as a vaccine delivery system

Eldridge, John H.; Staas, Jay K.; Meulbroek, Jonathan A.; McGhee, Jerry R.; Tice, Thomas R.; Gilley, Richard M.

doi:10.1016/0161-5890(91)90076-v

Cited by 383 publications

(152 citation statements)

References 16 publications

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“…Nebulization of pharmacological agents encapsulated in PLG has been described, particularly for airway delivery of antituberculous therapy, 23 but the effect of nebulization on PLG-encapsulated plasmid DNA has not yet been studied. While encapsulation of the DNA potentially offers a way to both protect DNA from degradation 15 and also control its release, 7 analysis of DNA extracted from our microspheres, as well as in previous studies, 6 revealed a relative increase in the amount of nicked DNA compared to supercoiled. Whether this translates into loss of transfection efficiency remains unclear.…”

Section: Discussionsupporting

confidence: 56%

“…DNA has also been formulated with the synthetic, biodegradable polymer, poly(lactide-co-glycolide) (PLG) to generate microparticles capable of sustained gene delivery and expression. [5][6][7] PLG, which has a history of safe application in humans, 8 has been used extensively in the development of vaccine technology, [9][10][11] and may be loaded with biologically active molecules of widely different molecular size including insulin, 12 prolidase, 13 camptothesin 14 and rhVEGF. 15 pDNA encapsulated in PLG remains stable, and protected from enzymatic degradation.…”

Section: Introductionmentioning

confidence: 99%

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Poly (D, L-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo

et al. 2003

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Poly (D, L-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo

et al. 2003

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“…13 PLGA is a biocompatible and biodegradable material with an extensive record of safe use in medicine, 14 and PLGA particles less than 10 mm in diameter are actively taken up by cells such as macrophages. 15 The entrapment of DNA-hsp65 into PLGA microspheres does not interfere with its functionality. When administered in BALB/c mice, DNA-hsp65-loaded microspheres were able to elicit specific immune response with IFN-g production, giving a ten-fold reduction in the DNA amount when compared to intramuscular injection of naked DNA-hsp65.…”

Section: Introductionmentioning

confidence: 99%

Single dose of a vaccine based on DNA encoding mycobacterial hsp65 protein plus TDM-loaded PLGA microspheres protects mice against a virulent strain of Mycobacterium tuberculosis

et al. 2003

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The high incidence of tuberculosis around the world and the inability of BCG to protect certain populations clearly indicate that an improved vaccine against tuberculosis is needed. A single antigen, the mycobacterial heat shock protein hsp65, is sufficient to protect BALB/c mice against challenge infection when administered as DNA vaccine in a threedose-based schedule. In order to simplify the vaccination schedule, we coencapsulated hsp65-DNA and trehalose dimicolate (TDM) into biodegradable poly(DL-lactide-co-glycolide) (PLGA) microspheres. BALB/c mice immunized with a single dose of DNA-hsp65/TDM-loaded microspheres produced high levels of IgG2a subtype antibody and high amounts of IFN-g in the supernatant of spleen cell cultures. DNA-hsp65/TDM-loaded microspheres were also able to induce high IFN-g production in bulk lung cells from challenged mice and confer protection as effective as that attained after three doses of naked DNA administration. This new formulation also allowed a ten-fold reduction in the DNA dose when compared to naked DNA. Thus, this combination of DNA vaccine and adjuvants with immunomodulatory and carrier properties holds the potential for an improved vaccine against tuberculosis. Gene Therapy (2003) 10, 678-685.

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“…They are biocompatible, biodegradable and able to incorporate different kinds of antigens with higher loading efficiency. They have advantages over conventional adjuvants, mainly in the manipulation of degradation kinetics by varying the concentration of monomers and cross-linkers [41]. In this way, the release profile of an antigen can be modulated.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant properties of a biocompatible thermo-responsive polymer of N -isopropylacrylamide in autoimmunity and arthritis

Shakya

Kumar

Nandakumar

2011

J. R. Soc. Interface.

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To evaluate the thermo-responsive poly(N-isopropylacrylamide) (PNiPAAm) polymer as an adjuvant, we synthesized PNiPAAm through free radical polymerization and characterized it both in vitro and in vivo. The polymer when mixed with collagen type II (CII) induced antigen-specific autoimmunity and arthritis. Mice immunized with PNiPAAm-CII developed significant levels of CII-specific IgG response comprising major IgG subclasses. Antigen-specific cellular recall response was also enhanced in these mice, while negligible level of IFN-g was detected in splenocyte cultures, in vitro. PNiPAAm-CII-immunized arthritic mouse paws showed massive infiltration of immune cells and extensive damage to cartilage and bone. As determined by immunostaining, most of the CII protein retained its native configuration after injecting it with PNiPAAm in naive mice. Physical adsorption of CII and the highmolecular-weight form of moderately hydrophobic PNiPAAm induced a significant anti-CII antibody response. Similar to CII, mice immunized with PNiPAAm and ovalbumin (PNiPAAm-Ova) induced significant anti-ovalbumin antibody response. Comparable levels of serum IFN-g, IL-1b and IL-17 were observed in ovalbumin-immunized mice with complete Freund, incomplete Freund (CFA and IFA) or PNiPAAm adjuvants. However, serum IL-4 levels were significantly higher in PNiPAAm-Ova and CFA-Ova groups compared with the IFA-Ova group. Thus, we show for the first time, biocompatible and biodegradable thermo-responsive PNiPAAm can be used as an adjuvant in several immunological applications as well as in better understanding of the autoimmune responses against self-proteins.

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Biodegradable microspheres as a vaccine delivery system

Cited by 383 publications

References 16 publications

Poly (D, L-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo

Poly (D, L-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo

Single dose of a vaccine based on DNA encoding mycobacterial hsp65 protein plus TDM-loaded PLGA microspheres protects mice against a virulent strain of Mycobacterium tuberculosis

Adjuvant properties of a biocompatible thermo-responsive polymer of N -isopropylacrylamide in autoimmunity and arthritis

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