Therapeutic implications of nanomedicine for ocular drug delivery

Meng, Tuo; Kulkarni, Vineet; Simmers, Russell; Brar, Vikram S; Xu, Qingguo

doi:10.1016/j.drudis.2019.05.006

Cited by 97 publications

(64 citation statements)

References 79 publications

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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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“…Concerns for the use of materials with longer residence times in the eye have arisen around the potential for incomplete breakdown of devices designed to biodegrade in order to release their drug load, and the uncertainty of responses to the by‐products of different materials' decomposition. In a repeated dosing situation, such as with eye drops there is a risk of material build up and an associated inflammatory response 116. Material may build in the conjunctival sac, which poses a potential risk as the conjunctiva is more prone to inflammatory responses than the cornea 20.…”

Section: The Immunological Response To Polymeric Materialsmentioning

confidence: 99%

“…[115] Different shapes, charges, and functional groups can influence the immunological response to nanocarriers and the response in inflamed tissue can vary from the response in noninflamed tissues-an important consideration for treating different pathologies. [116]…”

Section: Polymeric Microspheres and Nanocarriersmentioning

confidence: 99%

“…In a repeated dosing situation, such as with eye drops there is a risk of material build up and an associated inflammatory response. [116] Material may build in the conjunctival sac, which poses a potential risk as the conjunctiva is more prone to inflammatory responses than the cornea. [20] This could also lead to a foreign body response and a feeling of discomfort, which will not aid adherence to a treatment regime.…”

Section: Biomaterials In the Eyementioning

confidence: 99%

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Material, Immunological, and Practical Perspectives on Eye Drop Formulation

Bennett

Chinnery

Downie

et al. 2020

Adv Funct Materials

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Eye drops are the most common and inexpensive approach to topical ocular drug delivery. Eye drops offer a noninvasive treatment strategy; however, this can be detrimental to therapeutic efficacy when compared to invasive methods such as surgeries, implants, and injections. Improvements to the efficacy of the topical delivery of drugs to ocular tissues are currently being explored and much of this work centers on adjusting the formulation of the eye drops and prolonging the bioavailability of the therapeutic agent. This is often in preference to improving other patient‐focused or clinical factors. In this progress report, conventional, commercially available polymer eye drops are explored and the ability for current and future innovations to maintain the existing benefits of eye drops to the patient is assessed. The final materials and form of the drops (liquid, gel, or other) and the immunological implications for the user are explored. There is currently no consensus for how to most effectively improve the ocular retention and drug delivery capabilities of eye drops, but key issues are highlighted in the context of current methods under development, and potential questions and considerations for future innovations are raised.

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“…Topical eyedrops have poor ocular bioavailability owing to the rapid tear film turnover, corneal barrier, and quick tear drainage [17]. Nanomedicine can increase solubility of hydrophobic drug in aqueous solution, sustained drug release with improved efficacy and reduced toxicity, enhance drug penetration through ocular barriers and extend drug retention time, and even some nanomedicines can target specific cells and tissues.…”

Section: Nanomedicine In Ocular Surface Diseasementioning

confidence: 99%

Nanomedicine: Future Promising Therapy on Treating Meibomian Gland Dysfunction

Chen¹

2019

NNOA

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Meibomian gland dysfunction (MGD) is a chronic inflammation-related disease, which can cause instability of tear film, discomfort of the ocular surface and eyelids, and finally lead to dry eye disease (DED). The current clinical therapy has the following disadvantages, such as time-consuming, general treatment effect, and expensive treatment. Nanomedicine has been used in the treatment of some ocular surface diseases. For example, nanoparticles have been used in some eye drops formulations as well as eye patches, which can enhance the water solubility of the drugs, prolong the action time, and reduce the toxicity. In this review, we have introduced MGD and its' current clinical therapy. Since nanomedicine has already participated in treating DED patients and got satisfactory outcome, we believe that it will also have promising prospects in treating MGD.

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Therapeutic implications of nanomedicine for ocular drug delivery

Cited by 97 publications

References 79 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

Material, Immunological, and Practical Perspectives on Eye Drop Formulation

Nanomedicine: Future Promising Therapy on Treating Meibomian Gland Dysfunction

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