Highly bioactive, bevacizumab-loaded, sustained-release PLGA/PCADK microspheres for intravitreal therapy in ocular diseases

Liu, Jiaxin; Li, Shuang; Li, Ge; Li, Xiang; Yu, Changhui; Fu, Zhijiang; Li, Xiangyu; Teng, Lirong; Li, Youxin; Sun, Fengying

doi:10.1016/j.ijpharm.2019.04.012

Cited by 33 publications

(14 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By using other administration routes, mainly intravitreal and periocular, PLGA microspheres have demonstrated their potential for the treatment of several ocular diseases due to the ability of these systems to deliver multiple active substances directly to the target site during the long term [20,22]. Previous studies have demonstrated that microspheres for therapeutic purposes were well tolerated after intravitreal injection [20,35,47,48]. The amount of PLGA microspheres is also an important factor to be considered.…”

Section: Discussionmentioning

confidence: 99%

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

et al. 2021

View full text Add to dashboard Cite

Progressive degeneration of neuroretinal tissue with maintained elevated intraocular pressure (IOP) to simulate chronic glaucoma was produced by intracameral injections of poly (lactic-co-glycolic) acid (PLGA) microspheres (Ms) in rat eyes. The right eye of 39 rats received different sizes of PLGA-Ms (2 µL suspension; 10% w/v): 14 with 38–20 µm Ms (Ms38/20 model) and 25 with 20–10 µm particles (Ms20/10 model). This novel glaucoma animal model was compared to the episcleral vein sclerosis (EPI) model (25 eyes). Injections were performed at baseline, two, four and six weeks. Clinical signs, IOP, retina and optic nerve thicknesses (using in vivo optical coherence tomography; OCT), and histological studies were performed. An IOP increment was observed in all three groups, however, the values obtained from the PLGA-Ms injection resulted lower with a better preservation of the ocular surface. In fact, the injection of Ms20/10 created a gentler, more progressive, and more sustained increase in IOP. This IOP alteration was correlated with a significant decrease in most OCT parameters and in histological ganglion-cell count for the three conditions throughout the eight-week follow-up. In all cases, progressive degeneration of the retina, retinal ganglion cells and optic nerve, simulating chronic glaucoma, was detected by OCT and corroborated by histological study. Results showed an alternative glaucoma model to the well-known episcleral vein model, which was simpler to perform, more reproducible and easier to monitor in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The primary, secondary, and tertiary structural stability of bevacizumab was analyzed using size exclusion chromatography (SEC-HPLC), circular dichroism (CD) (J-810, Jasco, USA), and fluorescence spectroscopy (RF-5301, Shimadzu, Japan) as previously described 25…”

Section: Methodsmentioning

confidence: 99%

<p>Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications</p>

Liu

Zhang

et al. 2019

IJN

Self Cite

View full text Add to dashboard Cite

PurposeAge-related macular degeneration is a multifactorial disease involving inflammation and choroidal neovascularization. Vascular endothelial growth factor (VEGF) has been regarded as a potential therapeutic target to treat choroidal neovascularization. Dexamethasone can interfere with the expression or action of VEGF while bevacizumab targets and combines with VEGF. We propose electrostatically-conjugated bevacizumab-bearing dexamethasone-loaded poly (D,L-lactide-co-glycolide)/polyethylenimine nanoparticles (eBev-DPPNs) for angiogenic combination treatment of ocular diseases.MethodsWe prepared a novel nanoparticle composed of poly (D, L-lactide-co-glycolide) and polyethylenimine and loaded the nanoparticles with dexamethasone. Bevacizumab was adsorbed onto the surfaces of the nanoparticles by electrostatic interactions. The eBev-DPPNs were evaluated according to their size, polydispersity index, zeta potential, morphology, drug loading, release behavior, and stability. The structural stability of bevacizumab on the surface of the nanoparticles was also analyzed. Subsequently, angiogenesis was investigated in the presence of the eBev-DPPNs using cell apoptosis, wound healing, Transwell invasion, and tube formation assays on the human umbilical vein endothelial cells (HUVECs) in vitro and chick embryo chorioallantoic membrane assay in vivo. The eBev-DPPNs intravitreal injection was applied in the laser-induced rabbit choroidal neovascularization (CNV) model to confirm the role for potential intravitreal applications.ResultsThe eBev-DPPNs was about 200 nm in diameter, with a narrow diameter distribution, and the surface charge was neutral (0.85 ± 0.37mV), which made the eBev-DPPNs stable under physiological conditions. The apoptosis, migration, invasion, and tube formation assays showed that the eBev-DPPNs had a good anti-angiogenic effect on HUVECs. The eBev-DPPNs also provided a strong inhibitory effect on VEGF secretion from HUVECs. Moreover, in vivo chick embryo chorioallantoic membrane assay showed eBev-DPPNs greatly reduced the amount of blood vessels. The leakage area of CNV decreased in the eBev-DPPNs group on rabbit CNV model.ConclusionThe eBev-DPPNs are a promising novel anti-angiogenesis therapeutic for potential intravitreal applications such as age-related macular degeneration.

show abstract

“…In the literature, many efforts have been made to develop different strategies to modulate the protein release profile. Most of them relied on polymer blend strategies [18] [19] [20] [21], whereas the strategy of mixing different types of PLGA-based microspheres was rarely addressed. Nevertheless, releasing a protein according to a zeroorder profile without protein denaturation during the polymer degradation process is still very challenging.…”

Section: Introductionmentioning

confidence: 99%

Modulation of protein release from penta-block copolymer microspheres

Minh-Quan

Gimel

Garric

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

View full text Add to dashboard Cite

Releasing a protein according to a zero-order profile without protein denaturation during the polymeric microparticle degradation process is very challenging. The aim of the current study was to develop protein-loaded microspheres with new PLGA based pentablock copolymers for a linear sustained protein release. Lysozyme was chosen as model protein and 40 µm microspheres were prepared using the solid-in-oil-in-water solvent extraction/evaporation process. Two types of PLGA-P188-PLGA penta-block copolymers were synthetized with two PLGA-segments molecular weight (20 kDa or 40 kDa). The resulting microspheres (50P20-MS and 50P40-MS) had the same size, an encapsulation efficiency around 50-60% but different porosities. Their protein release profiles were complementary: linear but non complete for 50P40-MS, non linear but complete for 50P20-MS. Two strategies, polymer blending and microsphere mixing, were considered to match the release to the desired profile. The (1:1) microsphere mixture was successful. It induced a bi-phasic release with a moderate initial burst (around 15%) followed by a nearly complete linear release for 8 weeks. This study highlighted the potential of this penta-block polymer where the PEO block mass ratio influence clearly the Tg and consequently the microsphere structure and the release behavior at 37°C. The (1:1) mixture was a starting point but could be finely tuned to control the protein release.

show abstract

Highly bioactive, bevacizumab-loaded, sustained-release PLGA/PCADK microspheres for intravitreal therapy in ocular diseases

Cited by 33 publications

References 27 publications

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

<p>Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications</p>

Modulation of protein release from penta-block copolymer microspheres

Contact Info

Product

Resources

About