Characterization of liposomal carriers for the trans-scleral transport of Ranibizumab

Joseph, Rini; Tan, Dulcia Wei Ni; Ramon, Moreno Raja Miguel; Natarajan, Jayaganesh V.; Agrawal, Rupesh; Wong, Tina; Venkatraman, Subbu S.

doi:10.1038/s41598-017-16791-7

Cited by 34 publications

(16 citation statements)

References 29 publications

(13 reference statements)

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“…Molecules smaller than 75 kDa can passively disperse through the sclera into the subretinal space. Molecules greater than 75 kDa can be dispersed through the sclera by changing the electrical charges using electrical/electromagnetic iontophoresis such as Magnovision™ [59][60][61][62][63][64]. Growth factors secreted by MSCs in the subretinal space activate the cells in the dormant phase and stimulate the progenitor cells (embriyonic remnants) in the retina [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]29].…”

Section: Discussionmentioning

confidence: 99%

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

Özmert

Arslan

2020

Stem Cell Res Ther

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Purpose: The aim of this study is to determine if umbilical cord Wharton's jelly derived mesenchymal stem cells implanted in sub-tenon space have beneficial effects on visual functions in retinitis pigmentosa patients by reactivating the degenerated photoreceptors in dormant phase. Material and methods:This prospective, open-label, phase-3 clinical trial was conducted between April of 2019 and October of 2019 at Ankara University Faculty of Medicine, Department of Ophthalmology. 32 RP patients (34 eyes) were included in the study. The patients were followed for 6 months after the Wharton's jelly derived mesenchymal stem cell administration, and evaluated with consecutive examinations. All patients underwent a complete routine ophthalmic examination, and best corrected visual acuity, optical coherens tomography angiography, visual field, multifocal and full-field electroretinography were performed. The quantitative results were obtained from a comparison of the pre-injection and final examination (6th month) values.Results: The mean best corrected visual acuity was 70.5 letters prior to Wharton's jelly derived mesenchymal stem cell application and 80.6 letters at the 6th month (p = 0.01). The mean visual field median deviation value was 27.3 dB before the treatment and 24.7 dB at the 6th month (p = 0.01). The mean outer retinal thickness was 100.3 μm before the treatment and 119.1 μm at 6th month (p = 0.01). In the multifocal electroretinography results, P1 amplitudes improved in ring1 from 24.8 to 39.8 nv/deg2 (p = 0.01), in ring2 from 6.8 to 13.6 nv/deg2 (p = 0.01), and in ring3 from 3.1 to 5.7 nv/deg2 (p = 0.02). P1 implicit times improved in ring1 from 44.2 to 32.4 ms (p = 0.01), in ring2 from 45.2 to 33.2 ms (p = 0.02), and in ring3 from 41.9 to 32.4 ms (p = 0.01). The mean amplitude improved in 16 Tds from 2.4 to 5.0 nv/deg2 (p = 0.01) and in 32 Tds from 2.4 to 4.8 nv/deg2 (p = 0.01) in the full-field flicker electroretinography results. Full field flicker electroretinography mean implicit time also improved in 16 Tds from 43.3 to 37.9 ms (p = 0.01). No ocular or systemic adverse events related to the two types of surgical methods and/or Wharton's jelly derived mesenchymal stem cells itself were observed during the follow-up period.Conclusion: RP is a genetic disorder that can result in blindness with outer retinal degeneration. Regardless of the type of genetic mutation, sub-tenon Wharton's jelly derived mesenchymal stem cell administration appears to be an effective and safe option. There are no serious adverse events or ophthalmic / systemic side effects for 6 months follow-up. Although the long-term adverse effects are still unknown, as an extraocular approach, subtenon implantation of the stem cells seems to be a reasonable way to avoid the devastating side effects of intravitreal/submacular injection. Further studies that include long-term follow-up are needed to determine the duration of efficacy and the frequency of application.

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Section: Discussionmentioning

confidence: 99%

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

Özmert

Arslan

2020

Stem Cell Res Ther

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“…Injections of some liposomal drug formulations have shown promise including early work with anti-VEGF agents. In experimental models, in vitro release of ranibizumab from negatively charged liposomes was exhausted at two days, whereas ex vivo transport across sclera (simulating a subconjunctival injection) occurred in a linear manner for seven days [ 34 ]. This suggests that sclera acts as a classic membrane that allows the diffusion of liposomal-formulated ranibizumab and raises the possibility that subconjunctival injections could serve as long-acting depots.…”

Section: Therapies Under Developmentmentioning

confidence: 99%

“…Liposomal formulation delays drug release Ranibizumab can cross sclera after subconjunctival depot [ 34 ] …”

Section: Tablementioning

confidence: 99%

Extended Duration Vascular Endothelial Growth Factor Inhibition in the Eye: Failures, Successes, and Future Possibilities

Stewart

2018

Pharmaceutics

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Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of neovascularization and edema from several common chorioretinal vascular conditions. The intravitreally injected drugs (aflibercept, bevacizumab, conbercept, pegaptanib, and ranibizumab) used to treat these conditions improve the visual acuity and macular morphology in most patients. Monthly or bimonthly injections were administered in the phase III pivotal trials but physicians usually individualize therapy with pro re nata (PRN) or treat and extend regimens. Despite these lower frequency treatment regimens, frequent injections and clinic visits are still needed to produce satisfactory outcomes. Newly developed drugs and refillable reservoirs with favorable pharmacokinetic profiles may extend durations of action and require fewer office visits. However, we have learned from previous experiences that the longer durations of action seen in strategically designed phase III trials often do not translate to less frequent injections in real-life clinical practice. Unfortunately, long-acting therapies that produce soluble VEGF receptors (encapsulated cell technology and adenovirus injected DNA) have failed in phase II trials. The development of longer duration therapies remains a difficult and frustrating process, and frequent drug injections are likely to remain the standard-of-care for years to come.

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“…Liposomes are novel carriers of targeting agents (15). The structure of liposomes is similar to that of biofilm and their membrane material is non-toxic in the human body (16).…”

Section: Introductionmentioning

confidence: 99%

Liver‑targeted delivery of liposome‑encapsulated curcumol using galactosylated‑stearate

You-wen

Guan

et al. 2018

Exp Ther Med

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Liver-targeted drug delivery improves the efficacy of anti-liver cancer agents and reduces systemic toxicity by limiting the bioavailability of these drugs to within tumors. Liver targeting reagents with galactose residues, which selectively combine to asialoglyco protein receptors, have previously been used to improve liposome-encapsulated drug accumulation within liver cells. They lead to a reduction in liver cancer cell growth and have been used to cure certain hepatic diseases. In the present study, curcumol, which is the primary active component of Chinese traditional medicine Rhizoma zedoariae, was encapsulated in galactosylated-liposomes to enhance its anti-liver cancer efficacy. Galactosylated-liposomes and normal liposomes were labeled with propidium iodide. Galactosylated-liposomes with increasing concentrations of galactosylated-stearate (Gal-s) had a notably increased level of uptake in HepG2 cells (hepatoblastoma) compared with SGC-7901 (gastric cancer) and A549 (non-small cell lung cancer) cells. When the percentage of Gal-s reached 20%, liposome uptake plateaued. In the anti-liver cancer experiment, the anti-liver cancer efficacy of galactosylated-curcumol-liposomes increased significantly more compared with normal curcumol liposomes and free curcumol as indicated by cell survival rate and lactate dehydrogenase release rate. Collectively, these results demonstrate that galactosylated-liposomes are able to enhance the liver-targeting effect and anti-liver cancer efficacy of curcumol.

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Characterization of liposomal carriers for the trans-scleral transport of Ranibizumab

Cited by 34 publications

References 29 publications

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

Extended Duration Vascular Endothelial Growth Factor Inhibition in the Eye: Failures, Successes, and Future Possibilities

Liver‑targeted delivery of liposome‑encapsulated curcumol using galactosylated‑stearate

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