Tetanus toxoid and synthetic malaria antigen containing poly(lactide)/poly(lactide-co-glycolide) microspheres: importance of polymer degradation and antigen release for immune response

Thomasin, Claudio; Corradin, Giampietro; Men, Ying; Merkle, Hans P.; Gander, Bruno

doi:10.1016/0168-3659(96)01363-6

Cited by 168 publications

(87 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The different burst release of the two differently sized microspheres (Table 1) may have been caused by the different particle surface areas [28,29], or by a different drug distribution inside the microspheres arising from the two processes of particle formation. In agreement with previous data [30], the kinetics after the burst was not affected by the particle size, suggesting that peptidepolymer interactions and related restricted peptide diffusion mainly controlled peptide release.…”

Section: In Vitro Release Kineticssupporting

confidence: 79%

Importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in PLA/PLGA microspheres

Blanco-Prieto

Campanero

Besseghir

et al. 2004

Journal of Controlled Release

Self Cite

View full text Add to dashboard Cite

The aim of the work was to develop biodegradable microspheres for controlled delivery of the somatostatin analogue vapreotide and maintenance of sustained plasma levels over 2 -4 weeks after a single injection in rats. Vapreotide was microencapsulated into end-group capped and uncapped low molecular weight PLA and PLGA by spray-drying and coacervation. Microspheres were prepared from single and blended (1:1) polymer types. The microparticles were characterized for peptide loading, in vitro release and pharmocokinetics in rats. Spray-drying and coacervation produced microspheres in the size range of 1 -15 μm and 10 -70 μm, respectively, and with encapsulation efficiencies varying between 46 and 87%. In vitro release of vapreotide followed a regular pattern and lasted more than 4 weeks, time at which 40 -80% of the total dose were released. Microspheres made of 14 kDa end-group uncapped PLGA50:50 or 1:1 blends of this polymer with 35 kDa endgroup uncapped PLGA50:50 gave the best release profiles and yielded the most sustained plasma levels above a pre-defined 1 ng/ml over approx. 14 days. In vitro/in vivo correlation analyses showed for several microsphere formulations a linear correlation between the mean residence time in vivo and the mean dissolution time (r=0.958) and also between the amount released between 6 h and 14 days and the AUC 6h-14d (r = 0.932). For several other parameters or time periods, no in vitro/in vivo correlation was found. This study demonstrates that controlled release of the vapreotide is possible in vivo for a duration of a least two weeks when administered i.m. to rats. These results constitute a step forward towards a twice-a-month or oncea-month microsphere-formulation for the treatment of acromegaly and neuroendocrine tumors.

show abstract

Section: In Vitro Release Kineticssupporting

confidence: 79%

Importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in PLA/PLGA microspheres

Blanco-Prieto

Campanero

Besseghir

et al. 2004

Journal of Controlled Release

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, PLGA microparticles completely degrade inside DCs within 10 days (3). In contrast, PLA microparticles degrade very slowly over several weeks (23). These data imply that the material, composition and rate of degradation of the carrier itself may play an important role to induce stimulation of DCs.…”

Section: Discussionmentioning

confidence: 72%

“…The search for efficient and safe synthetic vaccine carrier systems has yielded various types of biodegradable anionic and cationic microparticles, which are able to induce noticeable immune responses in vivo when loaded with peptide or protein antigens (10,23,33) or plasmid DNA (11,34). The adequate stimulation of DCs is of key importance for the initiation of acquired and innate immune responses by these cells.…”

Section: Discussionmentioning

confidence: 99%

“…The w/o dispersion was then spray-dried as stated above. Size distribution of the microparticle formulations was measured by laser light scattering (Mastersizer X, Malvern Instruments Ltd., Worcestershire, UK) and particle size was calculated based on Mie's theory (23). Zeta potential measurements were carried out in phosphate buffer at pH 7.4 (ionic strength ‫ס‬ 0.01) by using a Zeta-Meter system 3 + (ZM3 + 331, Zeta-Meter, Inc., Staunton, VA, USA) (3,24).…”

Section: Preparation and Characterization Of Microparticlesmentioning

confidence: 99%

“…Various biodegradable PLA and PLGA microparticles were prepared by a spray-drying method described elsewhere (21,23) (Table I). Briefly, for DNA encapsulation, DNA was dissolved in 0.1 M NaHCO 3 and the resulting solution was dispersed in a 5% (w/w) PLGA solution in ethyl formate by means of an ultrasonic processor (Vibra-Cell, Sonics & Material, Danbury CT, USA).…”

Section: Preparation and Characterization Of Microparticlesmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Surface modification of PLGA microspheres

Müller

Vörös

Csúcs

et al. 2003

J Biomedical Materials Res

View full text Add to dashboard Cite

Microspheres made of poly(lactic‐co‐glycolic acid) (PLGA) are biocompatible and biodegradable, rendering them a promising tool in the context of drug delivery. However, nonspecific adsorption of plasma proteins on PLGA micro‐ and nanospheres is a main limitation of drug targeting. Poly(L‐lysine)‐g‐poly(ethylene glycol) (PLL‐g‐PEG), physisorbed on flat metal oxide surfaces, has previously been shown to suppress protein adsorption drastically. The goal of our work was to characterize the efficiency of the protein repellent character of PLL‐g‐PEG on PLGA microspheres and to show the feasibility of introducing functional groups on the PLGA microspheres via functionalized PLL‐g‐PEG. To quantify the adsorbed amount of protein, a semiquantitative method that uses confocal laser scanning microscopy (CLSM) was applied. The first part of the experiment confirms the feasibility of introducing specific functional groups on PLL‐g‐PEG–coated PLGA microspheres. In the second part of the experiment, PLL‐g‐PEG–coated PLGA microspheres show a drastic decrease of adsorbed proteins by two orders of magnitude in comparison to uncoated PLGA microspheres. Low protein‐binding, functionalizable microspheres provide a fundamental basis for the design of drug delivery and biosensor systems. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 55–61, 2003

show abstract

Tetanus toxoid and synthetic malaria antigen containing poly(lactide)/poly(lactide-co-glycolide) microspheres: importance of polymer degradation and antigen release for immune response

Cited by 168 publications

References 31 publications

Importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in PLA/PLGA microspheres

Importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in PLA/PLGA microspheres

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

Surface modification of PLGA microspheres

Contact Info

Product

Resources

About