In vitro degradation of nanospheres from poly(D,L-lactides) of different molecular weights and polydispersities

Belbella, Abdelâaziz; Vauthier, Christine; Fessi, Hatem; Devissaguet, Jean‐Philippe; Puisieux, F.

doi:10.1016/0378-5173(95)04258-x

Cited by 126 publications

(69 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MNPs incubated in citrate buffer started to flocculate after 3 wk, likely because of the effect of acidic conditions weakening the electrosteric stabilization provided by MNP surface-associated albumin. In contrast, MNPs incubated at pH 7.4 degraded by 34.2 ± 2.2% over 80 d without significantly changing their size, consistent with the bulk hydrolysis degradation mechanism previously demonstrated for PLA-based nanospheres (7). In comparison with the decelerating degradation in PBS and citrate buffers, MNP disassembly in serum occurred at a steady rate (0.51-0.61% per day, P < 0.001; Fig.…”

Section: Resultssupporting

confidence: 61%

“…The kinetics of the hydrolytic NP degradation is governed by several concomitant processes and largely depends on a balance between the elimination of oligomeric breakdown products with a resulting increase in particle porosity, making its core more accessible to water, and the formation of new carboxylic groups that in their deprotonated form can create a negatively charged shield hindering the catalytic action of hydroxyl anions (7). The interplay between these two oppositely contributing effects may account for the different patterns of MNP degradation in liquid and semisolid media observed in our studies.…”

Section: Discussionmentioning

confidence: 99%

“…The degradation of PLA-based NP previously was shown to be dominated by bulk alkaline hydrolysis with random chain scission at neutral as well as moderately acidic conditions (6,7). The kinetics of the hydrolytic NP degradation is governed by several concomitant processes and largely depends on a balance between the elimination of oligomeric breakdown products with a resulting increase in particle porosity, making its core more accessible to water, and the formation of new carboxylic groups that in their deprotonated form can create a negatively charged shield hindering the catalytic action of hydroxyl anions (7).…”

Section: Discussionmentioning

confidence: 99%

“…The presence and expected duration of a "lag" (i.e., time to the commencement of the actual disassembly) will depend on multiple factors, related to the characteristics of the surrounding medium (32) as well as the properties of the particles (6)(7)(8). Thus, although our experiments did not reveal a significant delay in the onset of MNP disintegration, a detectable lag may be anticipated for NPs formed from a polymer with a larger initial molecular weight or a higher degree of crystallinity (6,8).…”

Section: Discussionmentioning

confidence: 99%

“…The few in vitro studies examining the stability and degradation of biodegradable polyester-based submicronial particles point to the complexity of the breakdown process (6)(7)(8). Degradation of NPs presents itself as simultaneous changes in particle size, molecular weight of the matrix-forming polymer and acidity, generation of increasingly hydrophilic degradation products, etc.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

Tengood

Alferiev

Zhang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The fate of nanoparticle (NP) formulations in the multifaceted biological environment is a key determinant of their biocompatibility and therapeutic performance. An understanding of the degradation patterns of different types of clinically used and experimental NP formulations is currently incomplete, posing an unmet need for novel analytical tools providing unbiased quantitative measurements of NP disassembly directly in the medium of interest and in conditions relevant to specific therapeutic/ diagnostic applications. In the present study, this challenge was addressed with an approach enabling real-time in situ monitoring of the integrity status of NPs in cells and biomimetic media using Förster resonance energy transfer (FRET). Disassembly of polylactidebased magnetic NPs (MNPs) was investigated in a range of model biomimetic media and in cultured vascular cells using an experimentally established quantitative correlation between particle integrity and FRET efficiency controlled through adjustments in the spectral overlap between two custom-synthesized polylactide-fluorophore (boron dipyrromethene) conjugates incorporated in MNPs. The results suggest particle disassembly governed by diffusion-reaction processes with kinetics strongly dependent on conditions promoting release of oligomeric fragments from the particle matrix. Thus, incubation in gels simulating the extracellular environment and in protein-rich serum resulted in notably lower and higher MNP decomposition rates, respectively, compared with nonviscous liquid buffers. The diffusion-reaction mechanism also is consistent with a significant cell growth-dependent acceleration of MNP processing in dividing vs. contact-inhibited vascular cells. The FRET-based analytical strategy and experimental results reported herein may facilitate the development and inform optimization of biodegradable nanocarriers for cell and drug delivery applications.nanoparticle degradation | direct assay | endothelial cell | smooth muscle cell | restenosis N anoparticles (NPs) of different compositions and designs are emerging as versatile diagnostic tools and promising carriers for delivery of small molecule drugs and biotherapeutics (1, 2). Among the prerequisites for their safe and effective use, an understanding of the fate of NPs intended for diagnostic or therapeutic applications is an obvious requirement, as it ensures the absence of acute or chronic toxicity caused by foreign materials retained in the body (3). Biodegradation of NPs developed as drug delivery carriers also plays a key role in their therapeutic performance by contributing to the biodistribution and fate of the cargo; thus, it is of essential importance for optimizing the site specificity and duration of the pharmacological effect for a given application (4).Despite the recognized need for definitive studies of NP degradation and factors governing its kinetics (5), investigative strategies providing reliable in situ measurements of NP disassembly are lacking. The few in vitro studies examining the stabili...

show abstract

Section: Resultssupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

Tengood

Alferiev

Zhang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

Influence of low molecular weight lactic acid derivatives on degradability of polylactide

Hakkarainen

Karlsson

Albertsson

2000

J. Appl. Polym. Sci.

View full text Add to dashboard Cite

ABSTRACT:The presence of low molecular weight lactic acid derivatives in films enhanced the degradability of polylactide in a biotic medium. Two different biotic and abiotic series were investigated. The films used for the first abiotic and biotic series (a-1 and b-1 films) initially contained some lactic acid and lactoyl lactic acid, while the films used for the second abiotic and biotic series (a-2 and b-2 films) did not originally contain them. The b-1 films decreased in molecular weight during 3 weeks in the biotic medium, while no molecular weight decrease was seen in the a-1 films aged in a corresponding abiotic mineral medium. The molecular weight for the a-2 and b-2 films without lactic and lactoyl lactic acid remained almost constant. Scanning electron microscopy micrographs showed a larger amount of bacteria and fungi growing on the surface of b-1 films compared to b-2 films; thus, the presence of easily assimilated lactic acid and lactoyl lactic acid in the films improved the initial growth of microorganisms on the film surfaces. Gas chromatography and mass spectrometry analysis showed that lactic acid and lactoyl lactic acid were rapidly assimilated from the films aged in a biotic medium. New degradation products (e.g., ethyl ester of lactoyl lactic acid, acetic acid, and propanoic acid) were formed during aging in a biotic medium. Acetic acid and propanoic acid were formed as intermediate degradation products during the initial stages, but they were no longer detected after prolonged aging. The concentration of the ethyl ester of lactoyl lactic acid increased with aging time.

show abstract

Influence of different physicochemical conditions on the release of indium oxine from nanocapsules

Kedzierewicz¹,

Thouvénot

Monot³

et al. 1998

J. Biomed. Mater. Res.

View full text Add to dashboard Cite

The main purpose of this study was to determine the influence of factors (pH, enzymes, etc.) chosen partially to mimic in vivo conditions on the release of a model drug, indium oxine, from polyepsiloncaprolactone (PCL) nanocapsules in vitro. A nanocapsule suspension, an emulsion (O/W), and a solution in olive oil were prepared in order to compare the release of a radioactive tracer, indium oxine, as a function of time by an in vitro dialysis method. Nanocapsules were prepared by interfacial deposition of PCL and characterized by particle size distribution (laser light scattering) and determination of the polymer molecular weight by gel permeation chromatography (GPC). The results of this study suggest that the partition coefficient between the acceptor medium and the olive oil is the major parameter governing the release of the isotope, at least in the absence of significant enzyme activity. The PCL wall of nanocapsules is a barrier that does not seem to retard the release of indium. The addition of porcine liver esterases accelerated the degradation of PCL. This study confirms that the release of a drug from nanocapsules may be very different depending on the in vivo location, that is, the administration site.

show abstract

In vitro degradation of nanospheres from poly(D,L-lactides) of different molecular weights and polydispersities

Cited by 126 publications

References 20 publications

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

Influence of low molecular weight lactic acid derivatives on degradability of polylactide

Influence of different physicochemical conditions on the release of indium oxine from nanocapsules

Contact Info

Product

Resources

About