Mathematical modeling of bioerodible, polymeric drug delivery systems

Siepmann, J.; Göpferich, Achim

doi:10.1016/s0169-409x(01)00116-8

Cited by 685 publications

(382 citation statements)

References 65 publications

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“…These polymers erode slowly and water uptake by the system is much faster than polymer degradation. In this case, erosion is not restricted to the polymer surface, because the entire system is rapidly hydrated and polymer chains are cleaved throughout the device [11]. This mechanism permits using PLGA in controlled-release applications.…”

Section: Introductionmentioning

confidence: 99%

“…Almost all known modelling approaches available [11,12,14] consider homogeneous distributions of the pores and of proteins in the spheres, experiments have indicated that this may not realistically describe the majority of cases [9,19], with internal configuration of the spheres subject to heterogeneity. In further discussion of microspheres properties, [13] assumes that adsorption of macromolecules to the surface of the microsphere (or to the large occlusions inside the spheres), suggesting an uneven distribution of the macromolecule in the volume of the sphere.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative multi-agent models for simulating protein release from PLGA bioerodible nano- and microspheres

Barat

Crane

Ruskin

2008

Journal of Pharmaceutical and Biomedical Analysis

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Summary. Using poly(lactide-co-glycolide) (PLGA) particles for drug encapsulation and delivery has recently gained considerable popularity for a number of reasons. An advantage in one sense, but a drawback of PLGA use in another, is that drug delivery systems made of this material can provide a wide range of dissolution profiles, due to their internal structure and properties related to particles' manufacture. The advantages of enriching particulate drug design experimentation with computer models, are evident with simulations used to predict and optimize design, as well as indicate choice of best manufacturing parameters. In the present work, we seek to understand the phenomena observed for PLGA micro-and nanospheres, through Cellular Automata (CA) agent-based Monte Carlo (MC) models. Systems are studied both over large temporal scales, (capturing slow erosion of PLGA) and for various spatial configurations (capturing initial as well as dynamic morphology). The major strength of this multi-agent approach is to observe dissolution directly, by monitoring the emergent behaviour: the dissolution profile manifested, as a sphere erodes. Different problematic aspects of the modelling process are discussed in details in this paper. The models were tested on experimental data from literature, demonstrating very good performance. Quantitative discussion is provided throughout the text in order to make a demonstration of the use in practice of the proposed model.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative multi-agent models for simulating protein release from PLGA bioerodible nano- and microspheres

Barat

Crane

Ruskin

2008

Journal of Pharmaceutical and Biomedical Analysis

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“…According to many authors, PLGA is a polymer characterized by bulk erosion (37). This is due to the presence of less reactive functional groups on the surface (38); as a result, the polymer chains inside the bulk of the matrix start to be cleaved by hydrolysis, producing acidic shorter-chain moieties, which start a series of autocatalytic hydrolysis reactions.…”

Section: Microsphere Degradationmentioning

confidence: 99%

Prednisolone-Loaded PLGA Microspheres. In Vitro Characterization and In Vivo Application in Adjuvant-Induced Arthritis in Mice

et al. 2010

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Abstract. This study aimed at preparation of a sustained-release steroidal treatment for chronic inflammatory conditions, such as rheumatoid arthritis. To achieve such a goal, biodegradable polylactide-co-glycolide prednisolone-loaded microspheres were prepared using o/w emulsion solvent evaporation method. Formulation parameters were adjusted so as to optimize the microsphere characteristics. The prepared microspheres exhibited smooth and intact surfaces, with average size range not exceeding 65 µm. The encapsulation efficiency percent of most microsphere formulations fell within the range of 25-68%. Drug release from these microspheres took place over 4 weeks, with nearto-zero-order patterns. Two successful formulations were chosen for the treatment of unilateral arthritis, induced in mice using Freund's complete adjuvant (FCA). Inflammatory signs of adjuvant arthritis included severe swelling of the FCA-injected limbs, in addition to many histopathological lesions. These included inflammatory cell infiltration, synovial hyperplasia, cartilage, and bone erosion. Parenteral administration of the selected formulae dramatically reduced the swelling of the FCA-injected limbs. In addition, histological examination revealed that the microsphere treatment protocol efficiently protected cartilages and bones of mice, injected with FCA initial and booster doses, from erosion. These results could not be achieved by a single prednisolone dose of 5 mg/kg.

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“…In addition, they also allow quantitative understanding of the physical, chemical and biological phenomena involved in the controlled release of ions or molecules (Siepmann and Göpferich 2001;Snorradóttir et al 2013). Due to significant advances in information technology, mathematical modelling of biomaterial behaviour is increasing its academic and industrial importance, which makes it an integral part of future research and development in bone tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

Computational modelling of local calcium ions release from calcium phosphate-based scaffolds

Manhas

Guyot

Kerckhofs

et al. 2016

Biomech Model Mechanobiol

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A variety of natural or synthetic calcium phosphate (CaP)-based scaffolds are currently produced for dental and orthopaedic applications. These scaffolds have been shown to stimulate bone formation due to their biocompatibility, osteoconductivity and osteoinductivity. The release of the Ca 2+ ions from these scaffolds is of great interest in light of the aforementioned properties. It can depend on a number of biophysicochemical phenomena such as dissolution, diffusion and degradation, which in turn depend on specific scaffold characteristics such as composition and morphology. Achieving an optimal release profile can be challenging when relying on traditional experimental work alone. Mathematical modelling can complement experimentation. In this study, the in vitro dissolution behaviour of four CaP-based scaffold types was investigated experimentally. Subsequently, a mechanistic finite element method model based on biophysicochemical phenomena and specific scaffold characteristics was developed to predict the experimentally observed behaviour. Before the model could be used for local Ca 2+ ions release predictions, certain parameters such as dissolution constant (k dc ) and degradation constant (k sc ) for each type of scaffold were determined by calibrating the model to the in vitro dissolution data. The resulting model showed to yield release characteristics in satisfactory agreement with those observed experimentally. This suggests that the mathematical model can be used to investigate the local Ca 2+ ions release from CaP-based scaffolds.

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Mathematical modeling of bioerodible, polymeric drug delivery systems

Cited by 685 publications

References 65 publications

Quantitative multi-agent models for simulating protein release from PLGA bioerodible nano- and microspheres

Quantitative multi-agent models for simulating protein release from PLGA bioerodible nano- and microspheres

Prednisolone-Loaded PLGA Microspheres. In Vitro Characterization and In Vivo Application in Adjuvant-Induced Arthritis in Mice

Computational modelling of local calcium ions release from calcium phosphate-based scaffolds

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