Controlled release of hyaluronan oligomers from biodegradable polymeric microparticle carriers

Hedberg, Elizabeth L.; Shih, Charles K.; Solchaga, Luis A.; Caplan, Arnold I.; Mikos, Antonios G.

doi:10.1016/j.jconrel.2004.08.020

Cited by 29 publications

(16 citation statements)

References 21 publications

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“…The HA concentration of solutions was analyzed by a carbazole method 40 that was a modification of the Bitteer and Muir method for the quantification of hexuronic acids. 41,42 Stock solutions of sodium tetraborahydrate in sulfuric acid and carbazole in ethanol were prepared.…”

Section: Hyaluronic Acid Analysismentioning

confidence: 99%

Fabrication and characterization of porous hyaluronic acid–collagen composite scaffolds

Tang

Vickers

Hsu

et al. 2007

J Biomedical Materials Res

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Hyaluronic acid (HA) plays a vital role in many tissues, influencing water content and mechanical function, and has been shown to have positive biological effects on cell behavior in vitro. To begin to determine whether these benefits can be accessed if HA is incorporated into collagen-based scaffolds for tissue engineering, HA-collagen composite matrices were prepared and selected properties evaluated. HA-collagen scaffolds were cross-linked with carbodiimide and loss rates of HA in culture medium assessed. Scaffold pore structures were evaluated by light and electron microscopy. Adult canine chondrocytes were grown in selected HA-collagen scaffolds to assess the effects of HA on cell behavior. Homogenous HA-collagen slurries were achieved when polyionic complexes were suppressed. HA was uniformly distributed through the scaffolds, which demonstrated honeycomb-like pores with interconnectivity among pores increasing as HA content increased. Virtually all of the HA added to the collagen slurry was incorporated into the composite scaffolds that underwent a 7-day cross-linking protocol. After 5 days in culture medium, the HA content in the scaffolds was 5-7% regardless of initial HA loading. After only 2 weeks in culture cartilaginous tissue was found in the chondrocyte-seeded HA-collagen scaffolds. This study contributes to the understanding of the effects of HA content, pH, and cross-link treatment on pore characteristics and degradation behavior essential for the design of HA-collagen scaffolds. The demonstration that these scaffolds can be populated by chondrocytes and support in vitro formation of cartilaginous tissue warrants further investigation of this material system for tissue engineering.

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Section: Hyaluronic Acid Analysismentioning

confidence: 99%

Fabrication and characterization of porous hyaluronic acid–collagen composite scaffolds

Tang

Vickers

Hsu

et al. 2007

J Biomedical Materials Res

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“…To compromise the brittle mechanical properties of PLGA, PEG of low glass transition temperature was often added as a plastizer to the PLGA matrix [6,7]. The PEG addition also resulted in accelerated or decelerated drug release in a controlled manner [7][8][9][10]. For instance, adding 2% PEG to PLGA microparticles increased the in vitro release rate of PTX, while higher portion of PEG slowed down the PTX release [10].…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel distribution in poly(ethylene glycol)/poly(lactide-co-glycolic acid) blends and its release visualized by coherent anti-Stokes Raman scattering microscopy

Kang¹,

Robinson²,

Park³

et al. 2007

Journal of Controlled Release

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Mechanisms underlying the release of paclitaxel (PTX) from poly(ethylene glycol)/poly(lactic-coglycolic acid) (PEG/PLGA) blends were investigated by coherent anti-Stokes Raman scattering (CARS) microscopy. PLGA, PEG, and PTX were selectively imaged by using the resonant CARS signal from the CH 3 , CH 2 , and aromatic CH stretch vibrations, respectively. Phase segregation was observed in PLGA films containing 10 to 40 wt.% PEG in the absence of PTX loading. The PEG phase existed in the form of crystalline fibers in the (8:2, weight ratio) and (7:3) PLGA/PEG films. CARS observation indicated that PTX preferentially partitioned into the PEG domains in the (9:1) and (8:2) PLGA/PTX films, but exhibited a uniform mixing with both PLGA and PEG in the (7:3) PLGA/PEG film. The solid dispersion of PTX into PEG domains was attributed to a strong interaction between PTX and PEG, supported by the disappearance of PEG crystallization in the PTX-loaded PLGA/PEG film evidenced through X-ray diffraction analysis. PTX release was induced by exposing the film to an aqueous solution and monitored in real time by CARS and two-photon fluorescence microscopy. Fast dissolution of both PEG and PTX was observed at the film surface. Upon infiltration of water into the film, the PEG domains rearranged into ring structures enriched by both PTX and PEG. The CARS data provided a visual evidence explaining the accelerated burst release followed by more sustained release of PTX from the PLGA/PEG films as measured by HPLC.

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“…For this application seeking to achieve extended release of the HA-o from NPs, we selected a copolymer weight ratio of 85:15 PLA to PGA, since it has been shown that increasing the lactide to glycolide ratio decreases the polymer degradation rate and therefore can slow the release of incorporated active agent [32]. We selected a high molecular weight (~87 kDa) form of the polymer to create NPs with the expectation that it would prolong duration of release of active agents since it has been shown that polymers of higher molecular weight degrade more slowly [33]. …”

Section: Discussionmentioning

confidence: 99%

“…The assay is based on the established modified Bitter-Muir carbazole method [18]. To determine the loading efficiency of HA-o within the NPs, supernatant saved from their synthesis were filtered in a 3kDa filter centrifuge tube (Amicon, Billerica, MA) and assayed for HA content.…”

Section: Methodsmentioning

confidence: 99%

Nanoparticles for localized delivery of hyaluronan oligomers towards regenerative repair of elastic matrix

et al. 2013

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Abdominal aortic aneurysms (AAAs) are rupture-prone progressive dilations of the infrarenal aorta due to a loss of elastic matrix that lead to weakening of the aortic wall. Therapies to coax biomimetic regenerative repair of the elastic matrix by resident, diseased vascular cells may thus be useful to slow, arrest, or regress AAA growth. Hyaluronan oligomers (HA-o) have been shown to induce elastic matrix synthesis by healthy and aneurysmal rat aortic smooth muscle cells (SMCs) in vitro but only via exogenous dosing, which potentially has side effects and limitations to in vivo delivery towards therapy. In this paper, we describe the development of HA-o loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for targeted, controlled, and sustained delivery of HA-o towards the elastogenic induction of aneurysmal rat aortic SMCs. These NPs were able to deliver HA-o over an extended period (>30 days) at previously determined elastogenic doses (0.2 – 20 μg/mL). HA-o released from the NPs led to dose dependent increases in elastic matrix synthesis, and the recruitment and activity of lysyl oxidase (LOX), the enzyme which crosslinks elastin precursor molecules into mature fibers/matrix. Therefore, we were able to successfully develop a nanoparticle based system for controlled and sustained HA-o delivery for the in vitro elastogenic induction of aneurysmal rat aortic smooth muscle cells (EaRASMCs).

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Controlled release of hyaluronan oligomers from biodegradable polymeric microparticle carriers

Cited by 29 publications

References 21 publications

Fabrication and characterization of porous hyaluronic acid–collagen composite scaffolds

Fabrication and characterization of porous hyaluronic acid–collagen composite scaffolds

Paclitaxel distribution in poly(ethylene glycol)/poly(lactide-co-glycolic acid) blends and its release visualized by coherent anti-Stokes Raman scattering microscopy

Nanoparticles for localized delivery of hyaluronan oligomers towards regenerative repair of elastic matrix

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