Anti-VEGFR2 Antibody-modified Micelle for Triggered Drug Delivery and Effective Therapy of Choroidal Neovascularization

2019 ◽  
Vol 16 (3) ◽  
pp. 258-265
Author(s):  
Kei Takahashi ◽  
Tomomi Masuda ◽  
Mitsunori Harada ◽  
Tadashi Inoue ◽  
Shinsuke Nakamura ◽  
...  

Objective: This study aimed to examine whether DC101 (anti-VEGFR2 antibody)- modified micelles have applications as novel drug delivery devices, which allow small molecule antiangiogenic agents to deliver to angiogenic sites on a murine laser-induced choroidal neovascularization (CNV) model. Materials and Method: CNV was induced by photocoagulation on the unilateral eye of each mouse under anesthesia. Immediately after laser coagulation, E7974-loaded DC101-modified micelles and motesanib-loaded DC101-modified micelles were intravitreally administrated. Two weeks after photocoagulation, CNV was visualized using fluorescein-conjugated dextran (MW=2,000 kDa), and the CNV area was measured in retinal pigment epithelium (RPE)-choroidal flat mounts. Results: Intravitreal administration of both DC101-modified micelles loaded with E7974 at 2 µM and motesanib at 2 µM significantly reduced CNV area in the murine laser-induced CNV model at a clearly lower concentration than the effective dose of each agent. Conclusion: These results suggest that DC101-modified micelle might be effective drug carrier system for treating CNV and other ocular angiogenic diseases.

Author(s):  
Dr.S.Bhagavathy Sivathanu ◽  
Shivapriya G ◽  
Shivapriya G

Liposome is a spherical vesicle which contains atleast one lipid bilayer. Liposomes are used as a novel drug carriers because of its hydrophobic and hydrophilic nature, it has many advantages in the field of medical sciences. There are some other drug carriers like dendrimers, micelles, niosomes. Out of all, liposomes are considered to be the most promising agent for drug delivery. The uniqueness of liposome is when it is used as a pharmaceutical drug, it acts as a natural receptor. Thus it acts as an antigen and binds with the antibody (cancer cell) without causing any damage to the adjacent cells. For the synthesis of liposomes, a phospholipid is required. The liposomes can be synthesized using egg yolk and chloroform. So the basic phospholipid is obtained from egg yolk. For more stability, the liposomes are prepared using popc. The present work  discuss about the effective preparation of drug loaded liposomes using popc (1- palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine). POPC is an important phospholipid for biophysical experiments. Additionally chloroform is used as the solvent for the liposome preparation. The drug chosen for liposome loading is vitexin (vxn), which is an effective therapeutic agent against inflammation and cancer. The vesicular size, shape, drug entrapment efficacy, stability, electrochemical property and drug releasing property of the formulated liposomes were characterized. The results showed that the formulated liposomes are considered as the better drug carrier system and good choice for biotransformation within the cell to reach the target site such as cancer cells. Even though available treatments like chemotherapy and radiation therapy, causes damage to the surrounding cells, the alternative drug transferring system such as liposomal mediated drug transfer within the cell is considered as good choice of treatment to avoid such complications. The aim of liposome mediated  drug carrier system is to develop a method to reach the drug to the target site. After drug delivery at the target site, the liposomes are fused within the surface of the body. This is because of the pH of liposomes, which is at 7.4 and temperature is maintained at 37 oC. So, the vxn loaded liposomes are considered as the novel drug carriers for the successful targetted drug delivery.


2021 ◽  
Vol 22 (4) ◽  
pp. 1776
Author(s):  
Elham Pishavar ◽  
Hongrong Luo ◽  
Johanna Bolander ◽  
Antony Atala ◽  
Seeram Ramakrishna

Progenitor cells derived from the retinal pigment epithelium (RPECs) have shown promise as therapeutic approaches to degenerative retinal disorders including diabetic retinopathy, age-related macular degeneration and Stargardt disease. However, the degeneration of Bruch’s membrane (BM), the natural substrate for the RPE, has been identified as one of the major limitations for utilizing RPECs. This degeneration leads to decreased support, survival and integration of the transplanted RPECs. It has been proposed that the generation of organized structures of nanofibers, in an attempt to mimic the natural retinal extracellular matrix (ECM) and its unique characteristics, could be utilized to overcome these limitations. Furthermore, nanoparticles could be incorporated to provide a platform for improved drug delivery and sustained release of molecules over several months to years. In addition, the incorporation of tissue-specific genes and stem cells into the nanostructures increased the stability and enhanced transfection efficiency of gene/drug to the posterior segment of the eye. This review discusses available drug delivery systems and combination therapies together with challenges associated with each approach. As the last step, we discuss the application of nanofibrous scaffolds for the implantation of RPE progenitor cells with the aim to enhance cell adhesion and support a functionally polarized RPE monolayer.


Author(s):  
Mahdieh Azimizadeh ◽  
Seyedeh Maryam Hosseini ◽  
Esmaeil Babaei

Purpose: To report a case of choroidal osteoma associated with reactivation of choroidal neovascularization (CNV) and development of focal choroidal excavation (FCE). Case Report: A 34-year-old woman with choroidal osteoma complicated by CNV in the right eye for two years presented with deterioration of visual acuity in her right eye. A small retinal hemorrhage accompanied by subretinal fluid (SRF) was seen in the macular area of the right eye. Optical coherence tomography (OCT) showed that the inner retina was intact, and the outer retinal layers had outward displacement. SRF and a wedge-shaped choroidal depression were also seen. This choroidal excavation was not present on previous OCT images. The integrity of the inner retinal layers was maintained, and an optically clear space was present between the neurosensory retina and the retinal pigment epithelium. Conclusion: Choroidal osteoma can be complicated by CNV and FCE could occur as a consequence. Again, FCE can lead to CNV development. This cascade can deteriorate vision and sometime lead to permanent visual loss.


2000 ◽  
Author(s):  
C. von Kerczek ◽  
L. Zhu ◽  
A. Ernest ◽  
C. Eggleton ◽  
L. D. T. Topoleski ◽  
...  

Abstract Age-related macular degeneration (AMD) is the most common cause of vision loss in patients aged 65 years and older in the United States. In the majority of cases, the loss of central vision is secondary to exudative changes and fibrovascular scarring following choroidal neovascularization (CNV). Prompt laser treatment is recommended [Asrani et al., 1996; Macular Photocoagulation Study Group, 1993; Schneider et al, 1998]. However, direct laser treatment to the entire subfoveal lesion is almost invariably associated with immediate loss of central vision. Loss of central vision may be due to direct damage to foveal photoreceptors and retinal pigment epithelium or from damage to the nerve fiber layer serving foveal function [Han et al., 1988].


Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 694 ◽  
Author(s):  
Liang Ding ◽  
Xinxia Cui ◽  
Rui Jiang ◽  
Keya Zhou ◽  
Yalei Wen ◽  
...  

Liposomes are extensively used in drug delivery, while alginates are widely used in tissue engineering. However, liposomes are usually thermally unstable and drug-leaking when in liquids, while the drug carriers made of alginates show low loading capacities when used for drug delivery. Herein, we developed a type of thermo-responsible liposome–alginate composite hydrogel (TSPMAH) by grafting thermo-responsive liposomes onto alginates by using Ca2+ mediated bonding between the phosphatidic serine (PS) in the liposome membrane and the alginate. The temperature-sensitivity of the liposomes was actualized by using phospholipids comprising dipalmitoylphosphatidylcholine (DPPC) and PS and the liposomes were prepared by a thin-film dispersion method. The TSPMAH was then successfully prepared by bridge-linking the microcapsules onto the alginate hydrogel via PS-Ca2+-Carboxyl-alginate interaction. Characterizations of the TSPMAH were carried out using scanning electron microscopy, transform infrared spectroscopy, and laser scanning confocal microscopy, respectively. Their rheological property was also characterized by using a rheometer. Cytotoxicity evaluations of the TSPMAH showed that the composite hydrogel was biocompatible, safe, and non-toxic. Further, loading and thermos-inducible release of model drugs encapsulated by the TSPMAH as a drug carrier system was also studied by making protamine–siRNA complex-carrying TSPMAH drug carriers. Our results indicated that the TSPMAH described herein has great potentials to be further developed into an intelligent drug delivery system.


2015 ◽  
Vol 2015 ◽  
pp. 1-27 ◽  
Author(s):  
Karolina Werengowska-Ciećwierz ◽  
Marek Wiśniewski ◽  
Artur P. Terzyk ◽  
Sylwester Furmaniak

Nanomedicine is, generally, the application of nanotechnology to medicine. The term nanomedicine includes monitoring, construction of novel drug delivery systems, and any possible future applications of nanotechnology and nanovaccinology. In this review, the most important ligand-nanocarrier and drug-nanocarrier bioconjugations are described. The detailed characterizations of covalently formed bonds between targeted ligand and nanocarrier, including amide, thioether, disulfide, acetyl-hydrazone and polycyclic groups, are described. Also, the coupling of small elements and heteroatoms in the form of R-X-R the “click chemistry” groups is shown. Physical adsorption and chemical bonding of drug to nanocarrier surface involving drug on the internal or external surfaces of nanocarriers are described throughout possibility of the formation of the above-mentioned functionalities. Moreover, the most popular nanostructures (liposomes, micelles, polymeric nanoparticles, dendrimers, carbon nanotubes, and nanohorns) are characterized as nanocarriers. Building of modern drug carrier is a new method which could be effectively applied in targeted anticancer therapy.


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