Sustained local drug delivery to the arterial wall via biodegradable microspheres

Dev, V.; Eigler, Neal; Fishbein, Michael C.; Tian, Yu-Hua; Hickey, Anthony; Rechavia, Eldad; Forrester, James S.; Litvack, Frank

doi:10.1002/(sici)1097-0304(199707)41:3<324::aid-ccd14>3.0.co;2-n

Cited by 36 publications

(31 citation statements)

References 27 publications

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“…These microspheres are intended for localized delivery to fibronectin-enriched pathological tissues. Dexamethasone was selected as a model drug because it is useful for most chronic human diseases associated with fibronectin-cardiovascular disease, inflammation, and rheumatoid arthritis (14)(15)(16)). An oil/water emulsion/solvent evaporation method was used to prepare PLGA microspheres (17).…”

Section: Introductionsupporting

confidence: 64%

Preparation and characterization of gelatin surface modified PLGA microspheres

Tsung

Burgess

2001

AAPS PharmSci

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This study optimized conditions for preparing and characterizing gelatin surface modified poly (lactic-co-glycolic acid) (PLGA) copolymer microspheres and determined this system's interaction with fibronectin. Some gelatin microspheres have an affinity for fibronectin-bearing surfaces; these miscrospheres exploit the interaction between gelatin and fibronectin. PLGA copolymer microspheres were selected because they have reproducible and slowrelease characteristics in vivo. The PLGA microspheres were surface modified with gelatin to impart fibronectin recognition. Dexamethasone was incorporated into these microspheres because dexamethasone is beneficial in chronic human diseases associated with extra fibronectin expression (eg, cardiovascular disease, inflammatory disorders, rheumatoid arthritis). The gelatin surface modified PLGA microspheres (prepared by adsorption, conjugation, and spray coating) were investigated and characterized by encapsulation efficiency, particle size, in vitro release, and affinity for fibronectin. The gelatincoated PLGA microspheres had higher interaction with fibronectin compared with the other gelatin surface modified PLGA microspheres (adsorption and conjugation). Dexamethasone was released slowly (over 21 days) from gelatin surface modified PLGA microspheres.

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Section: Introductionsupporting

confidence: 64%

Preparation and characterization of gelatin surface modified PLGA microspheres

Tsung

Burgess

2001

AAPS PharmSci

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“…In addition to that, particle size is associated with biological response of the tissue to foreign biomaterials 19,20 . While inflammatory reactions with subsequent fibrosis is a typical response of vascular tissue to particulate delivery systems ranging in size between 5 and 10 µm 13,21 , nanoparticles usually cause little or no focal inflammation. Our study adds an additional aspect to the understanding of particle migration.…”

Section: Discussionmentioning

confidence: 99%

Deposition of nanoparticles in the arterial vessel by porous balloon catheters: Localization by confocal laser scanning microscopy and transmission electron microscopy

Westedt

Barbu–Tudoran

Schaper

et al. 2002

AAPS J

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Restenosis remains the major limitation of percutaneous transluminal angioplasty (PTA) and stenting in the treatment of patients with atherosclerotic disease. Catheter-based local delivery of pharmacologic agents offers a potential therapeutic approach to reducing restenosis and minimizing undesirable systemic side effects. However, the intramural retention of liquid agents is low. Therefore, to achieve a sustained and regional release of the therapeutic agent it must be encapsulated in nanoparticle carrier systems. The purpose of this study was to investigate the size dependence of the penetration of nanoparticles after local delivery into the vessel wall of the aorta abdominalis of New Zealand white rabbits. Two milliliters of a 0.025% fluorescence-labeled polystyrene nanoparticle suspension with diameters ranging from 110 to 514 nm were infused at 2 atm and at constant PTA pressure of 8 atm into the aorta abdominalis. After the infused segments were removed, the location of nanoparticles was visualized using confocal laser scanning microscopy and transmission electron microscopy. The study demonstrates a size-dependent nanoparticle penetration into the intact vessel wall. While nanoparticles of about 100 and 200 nm were deposited in the inner regions of the vessel wall, 514-nm nanoparticles accumulated primarily at the luminal surface of the aorta. The observations confirm that size plays a critical role in the distribution of particles in the arterial vessel wall. It is additionally influenced by the formation of pressure-induced infusion channels, as well as by the existence of anatomic barriers, such as plaques, at the luminal surface of the aorta or the connective elastic tissue.

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“…10,[22][23][24][25] Several groups have demonstrated the residence time 10,11 and antirestenotic effects 10,12-14 of particulate therapeutics. However, the local arterial pharmacokinet- …”

Section: Discussionmentioning

confidence: 99%

“…The early faster elimination of the smaller particles is probably due to easier migration to the adventitia, facilitating their elimination through the vasa vasorum, as demonstrated with fluorescent NPs and the work of other investigators. 10,12,14 The reduced late washout of the smaller NPs is probably due to their better penetration into deep arterial structures and creation of a drug depot that is relatively inaccessible to leaching by blood flow, the larger cumulative surface area of the smaller NPs, the direct cellular uptake of smaller particles, or some combination thereof. Given that the low tissue drug levels at advanced time points are considered to be a major reason for the failure of local antirestenotic therapy, our data advocate the use of the smaller-size carrier.…”

Section: Fishbein Et Al Tyrphostin Nanoparticles In Rat Model Of Restmentioning

confidence: 99%

Formulation and Delivery Mode Affect Disposition and Activity of Tyrphostin-Loaded Nanoparticles in the Rat Carotid Model

Fishbein

Chorny

Banai

et al. 2001

ATVB

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Abstract-Poor drug residence in the arterial wall hinders clinical implementation of local drug delivery strategies for the treatment of restenosis. A rat carotid model of vascular injury and intraluminal delivery of tyrphostin-containing polylactic acid (PLA) nanoparticles (NPs) were used to determine the relationship between residence properties and biological activity of different formulations and administration modes. The effects of delivery modes (denudation and delivery time) and formulation variables (adsorbed vs encapsulated drug, and NP size) on arterial drug/NP retention were examined. Antirestenotic effects of large (160 nm) and small (90 nm) tyrphostin-containing NPs, surface-absorbed tyrphostin, and systemic treatment were compared. Fluorescent NPs were used to study the spatial distribution of the carrier in the arterial wall. The decrease in arterial tyrphostin level over time fitted a biexponential model. Delivery time and pressure, endothelium integrity, particle size, and drug-polymer association affected local pharmacokinetics and the antirestenotic results after 14 days. The PLA-based tyrphostin NP formulation ensured a prolonged drug residence at the angioplasty site after single intraluminal application. Several readily adjustable formulation and procedural factors considerably modified arterial ingress of the drug-loaded NPs and governed their subsequent redistribution, tissue binding, elimination, and ensuing antirestenotic effect.

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Sustained local drug delivery to the arterial wall via biodegradable microspheres

Cited by 36 publications

References 27 publications

Preparation and characterization of gelatin surface modified PLGA microspheres

Preparation and characterization of gelatin surface modified PLGA microspheres

Deposition of nanoparticles in the arterial vessel by porous balloon catheters: Localization by confocal laser scanning microscopy and transmission electron microscopy

Formulation and Delivery Mode Affect Disposition and Activity of Tyrphostin-Loaded Nanoparticles in the Rat Carotid Model

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