Local and Sustained Vascular Endothelial Growth Factor Delivery for Angiogenesis Using an Injectable System

Lee, Jangwook; Lee, Kuen Yong

doi:10.1007/s11095-009-9884-4

Cited by 91 publications

(73 citation statements)

References 31 publications

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“…Thus, impurities such as heavy metals, endotoxins, proteins, and polyphenolic compounds may be present in alginate that could potentially cause an immune response (23). But, no foreign body reaction was observed when alginate was processed via multistep purification technique in an animal model (30,35). Therefore, based on the literatures, it appears that in some cases, alginate polymer may exert immunogenic responses, but in others, alginate appears to be non-immunogenic.…”

Section: Introductionmentioning

confidence: 99%

Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

El‐Sherbiny

2014

AAPS PharmSciTech

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ABSTRACT. Incorporation of drug-loaded nanoparticles into swellable and respirable microparticles is a promising strategy to avoid rapid clearance from the lung and achieve sustained drug release. In this investigation, a copolymer of polyethylene glycol grafted onto phthaloyl chitosan (PEG-g-PHCs) was synthesized and then self-assembled with ciprofloxacin to form drug-loaded nanoparticles. The nanoparticles and free drug were encapsulated into respirable and swellable alginate micro hydrogel particles and assessed as a novel system for sustained pulmonary drug delivery. Particle size, morphology, dynamic swelling profile, and in vitro drug release were investigated. Results showed that drug-loaded nanoparticles with size of 218 nm were entrapped into 3.9-μm micro hydrogel particles. The dry nano-in-micro hydrogel particles exhibited a rapid initial swelling within 2 min and showed sustained drug release. Preliminary in vivo pharmacokinetic studies were performed with formulations delivered to rats by intratracheal insufflation. Ciprofloxacin concentrations in plasma and in lung tissue and lavage were measured up to 7 h. The swellable particles showed lower ciprofloxacin levels in plasma than the controlled group (a mixture of lactose with micronized ciprofloxacin), while swellable particles achieved higher concentrations in lung tissue and lavage, indicating the swellable particles could be used for controlling drug release and prolonging lung drug concentrations.

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Section: Introductionmentioning

confidence: 99%

Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

El‐Sherbiny

2014

AAPS PharmSciTech

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“…Formulation of microspheres commonly involves the water-in-oil-in-water emulsion and solvent evaporation technique, which is suitable for incorporation of hydrophilic compounds. 39,40 PLGA microspheres may be used for the controlled release and in vivo localization of proteins 39,[41][42][43] and drugs. 40,44 Novel approaches to PLGA microsphere incorporation into three-dimensional biodegradable scaffolds include fusion of protein loaded spheres into scaffolds using dichloromethane vapor.…”

Section: Introductionmentioning

confidence: 99%

Sustained Delivery of Dibutyryl Cyclic Adenosine Monophosphate to the Transected Spinal Cord Via Oligo [(Polyethylene Glycol) Fumarate] Hydrogels

Rooney

Knight

Madigan

et al. 2011

Tissue Engineering Part A

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This study describes the use of oligo [(polyethylene glycol) fumarate] (OPF) hydrogel scaffolds as vehicles for sustained delivery of dibutyryl cyclic adenosine monophosphate (dbcAMP) to the transected spinal cord. dbcAMP was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres, which were embedded within the scaffolds architecture. Functionality of the released dbcAMP was assessed using neurite outgrowth assays in PC12 cells and by delivery to the transected spinal cord within OPF seven channel scaffolds, which had been loaded with Schwann cells or mesenchymal stem cells (MSCs). Our results showed that encapsulation of dbcAMP in microspheres lead to prolonged release and continued functionality in vitro. These microspheres were then successfully incorporated into OPF scaffolds and implanted in the transected thoracic spinal cord. Sustained delivery of dbcAMP inhibited axonal regeneration in the presence of Schwann cells but rescued MSC-induced inhibition of axonal regeneration. dbcAMP was also shown to reduce capillary formation in the presence of MSCs, which was coupled with significant functional improvements. Our findings demonstrate the feasibility of incorporating PLGA microsphere technology for spinal cord transection studies. It represents a novel sustained delivery mechanism within the transected spinal cord and provides a platform for potential delivery of other therapeutic agents.

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“…For this reason, combination delivery systems composed of both microspheres and hydrogels were fabricated by embedding PLGA microspheres into alginate gels. The combination systems were useful in controlling the release behavior of several proteins, including bovine serum albumin (BSA), heat shock protein 27 (HSP27), and rhVEGF (22)(23)(24). A microsphere/hydrogel combination system containing rhVEGF showed potential in promoting granulation tissue and blood vessel formation when the system was delivered into the subcutaneous tissue of mice (24).…”

Section: Discussionmentioning

confidence: 99%

“…For example, both VEGF and bFGF are completely released from alginate gels within 7 days in vitro (21). To overcome these limitations, we previously developed microsphere/hydrogel combination systems, consisting of PLGA microspheres and alginate hydrogels, as an injectable tool for sustained and localized delivery of protein drugs (22)(23)(24). In this paper, we report in vivo efficacy of microsphere/hydrogel combination systems containing rhVEGF in treatment of ischemic vascular diseases using the hindlimb ischemia mouse model, which is clinically relevant to therapeutic angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Active Blood Vessel Formation in the Ischemic Hindlimb Mouse Model Using a Microsphere/Hydrogel Combination System

et al. 2010

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Local and Sustained Vascular Endothelial Growth Factor Delivery for Angiogenesis Using an Injectable System

Abstract: The rhVEGF release was controlled by varying relative portions of microspheres and hydrogels in combination delivery systems, which efficiently promoted new blood vessel formation in vivo. This combination system could be a promising delivery vehicle for therapeutic angiogenesis.

Cited by 91 publications

References 31 publications

Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

Sustained Delivery of Dibutyryl Cyclic Adenosine Monophosphate to the Transected Spinal Cord Via Oligo [(Polyethylene Glycol) Fumarate] Hydrogels

Active Blood Vessel Formation in the Ischemic Hindlimb Mouse Model Using a Microsphere/Hydrogel Combination System

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