Delivery of Sphingosine 1-Phosphate from Poly(ethylene glycol) Hydrogels

Wacker, Bradley K.; Scott, Evan A.; Kaneda, Megan M.; Alford, Shannon K.; Elbert, Donald L.

doi:10.1021/bm050948r

Cited by 45 publications

(55 citation statements)

References 69 publications

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“…Sphingosine can then either be reacylated to ceramide or phosphorylated through the actions of sphingosine kinase (SphK) to generate S1P [44]. Studies with radioactive S1P reported that the bioactive lipid is rapidly degraded in the presence of smooth muscle cells to radioactive sphingosine, ceramide, and sphingomyelin [26,29,45,46]. Furthermore, S1P is insoluble in aqueous solutions in the absence of a carrier protein, such as albumin [40].…”

Section: Discussionmentioning

confidence: 99%

“…In one report, S1P release from hydrogels was shown to stimulate angiogenesis in a chick CAM assay [26]. Most recently, a second study demonstrated that exogenous administration of S1P stimulated blood flow recovery, accompanied by an increase in capillary density, in a mouse model of hindlimb ischemia [47].…”

Section: Discussionmentioning

confidence: 99%

“…Although S1P has been well-documented to stimulate endothelial cell proliferation, migration, and tube formation in vitro, cell behaviors indicative of an angiogenic phenotype, we did not see significant increases in length density, a metric of total microvascular length after 3 or 7 days (Figure 3). Despite model predictions of S1P concentration in the tissue space, the amount of albumin in solution could control the rate of release from polymer; results from a CAM assay of angiogenesis showed, at best, a moderate increase in capillary sprouting with S1P-loaded hydrogels (5 nmol), but a statistically significant increase in angiogenesis when 5 nmol S1P was co-encapsulated with fatty-acid free (FAF) bovine serum albumin (BSA) in the hydrogels [26]. These results suggest that the transport of S1P is facilitated by lipid carriers and further studies are warranted to optimize the encapsulation of S1P in PLAGA for applications of sustained release.…”

Section: Discussionmentioning

confidence: 99%

“…Degradation of 50:50 PLAGA was assumed to be negligible in the 7-day time-frame of the dorsal skinfold window chamber studies based on in vitro degradation data showing a significant lag phase up to day 14 [36]. D 1 = 7.7 × 10 −12 cm 2 /s was assumed for a drug of similar molecular weight diffusing from PLAGA [37] and D 2 = 6.4 × 10 −7 cm 2 /s was assumed for S1P bound to albumin through water [26]. The drug uptake term, k u , was assumed for FTY720, a structural analog of sphingosine, to be 1.3 × 10 −4 s −1 based on results from a one-compartment pharmacokinetic model with first-order absorption and elimination [38].…”

Section: Evaluation Of Release Kinetics and Mathematical Diffusion Modelmentioning

confidence: 99%

“…S1P is released by hemangioblastic cells, including platelets, mast cells, monocytes, and endothelial cells, in nanomolar concentrations into the bloodstream, but can additionally be secreted in higher concentrations by activated platelets in areas of endothelial injury to aid in wound repair [25]. S1P is thought to be a key signaling molecule, spanning both paradigms of angiogenesis and arteriogenesis, [26][27][28] making it an attractive therapeutic agent. S1P stimulates endothelial cell proliferation and migration [28,29], suggestive of an angiogenic role, and reduces oxygen and nutrient-deprived cell death [30].…”

Section: Introductionmentioning

confidence: 99%

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Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering

et al. 2008

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Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that impacts migration, proliferation, and survival in diverse cells types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. In this study, we investigated the effects of sustained release of S1P on microvascular remodeling and associated bone defect healing in vivo. The murine dorsal skinfold window chamber model was used to evaluate the structural remodeling response of the microvasculature. Our results demonstrated that 1:400 (w/w) loading and subsequent sustained release of S1P from poly(lactic-coglycolic acid) (PLAGA) significantly enhanced lumenal diameter expansion of arterioles and venules after 3 and 7 days. Incorporation of 5-bromo-2-deoxyuridine (BrdU) at day 7 revealed significant increases in mural cell proliferation in response to S1P delivery. Additionally, three-dimensional (3D) scaffolds loaded with S1P (1:400) were implanted into critical-size rat calvarial defects and healing of bony defects was assessed by radiograph x-ray, microcomputed tomography (μCT), and histology. Sustained release of S1P significantly increased the formation of new bone after 2 and 6 weeks of healing and histological results suggest increased numbers of blood vessels in the defect site. Taken together, these experiments support the use of S1P delivery for promoting microvessel diameter expansion and improving the healing outcomes of tissue-engineered therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Evaluation Of Release Kinetics and Mathematical Diffusion Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering

et al. 2008

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Photopolymerizable Hydrogels Made from Polymer‐Conjugated Albumin for Affinity‐Based Drug Delivery

Oss-Ronen¹,

Seliktar²

2010

Adv Eng Mater

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As a drug delivery vehicle, biodegradable albumin hydrogels can combine the high binding capacity of albumin with the structural stability of a polymeric hydrogel network to enable controlled release of small molecules based on both binding affinity and physical interactions. In the present study, we report on the development of a hybrid hydrogel composed of albumin conjugated to poly(ethylene glycol) (PEG) for drug delivery applications where controlled release is accomplished using the natural affinity of the drugs to the serum albumin. Bovine serum albumin was conjugated to PEG‐diacrylate having a molecular weight of 1.5, 4, or 10 kDa to form a PEGylated albumin macromolecule (mono‐PEGylated or multi‐PEGylated). Biodegradable hydrogels were formed from the PEGylated albumin using photopolymerization. Two model drugs, Warfarin and Naproxen, were used for equilibrium dialysis and release experiments from the hydrogels, both having relatively low molecular weights and a known high affinity for albumin. Equilibrium dialysis experiments showed that multi‐PEGylation of albumin significantly decreased the drug affinity to the protein compared to non‐PEGylated controls, irrespective of the PEG molecular weight. However, the results from drug release experiments showed that mono‐PEGylation of albumin did not change its natural affinity to the drug. Comparing the release profiles with a Fickian diffusion model provided strong evidence that hydrogels containing mono‐PEGylated albumin exhibited sub‐diffusive drug release properties based on the affinity of the drug to the tethered protein.

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Dual stimuli responsive glycidyl methacrylate chitosan‐quaternary ammonium hybrid hydrogel and its bovine serum albumin release

Chu²

2013

J of Applied Polymer Sci

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A new family of cationic hybrid hydrogels from two new positively charged aqueous soluble precursors, glycidyl methacrylate-chitosan (GMA-chitosan), and 2-(acryloyloxy) ethyl trimethylammonium (AETA), was developed via a simple photocrosslinking fabrication method. These hybrid hydrogels have pendant quaternary ammonium functional groups on the AETA segments. The chemical composition of GMA-chitosan/AETA hybrid hydrogels were characterized by Fourier transform infrared spectroscopy and their mechanical, swelling, and morphological properties were examined as a function of the composition of the hybrids as well as the effect of pH and ionic strength of the surrounding medium. GMA-chitosan/AETA hybrid hydrogels show a porous network structure with average pore diameter 20-50 lm. The compression moduli of these hybrid hydrogels ranged from 27.24 to 28.94 kPa, which are significantly higher than a pure GMA-chitosan (17.64 kPa). GMA-chitosan/AETA hybrid hydrogel shows pH/ionic strength responsive swelling behavior because of the presence of the positive charge pendant groups. These hybrid hydrogels showed a sustained BSA protein release and a significantly lower initial burst release than a pure GMA-chitosan hydrogel. The two aqueous soluble precursors and the cationic charge characteristics of the resulting GMA-chitosan/AETA hybrid hydrogels may suggest that this new family of biomaterials may have promising applications as the pH responsive protein drug delivery vehicles.

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Delivery of Sphingosine 1-Phosphate from Poly(ethylene glycol) Hydrogels

Cited by 45 publications

References 69 publications

Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering

Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering

Photopolymerizable Hydrogels Made from Polymer‐Conjugated Albumin for Affinity‐Based Drug Delivery

Dual stimuli responsive glycidyl methacrylate chitosan‐quaternary ammonium hybrid hydrogel and its bovine serum albumin release

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