Non-Invasive Ophthalmic Liposomes for Nucleic Acid Delivery to Posterior Segment of Eye

Takashima, Yuuki; Tsuchiya, Tomohiro; Igarashi, Yuko; Kanazawa, Takanori; Okada, Hiroaki; Urtti, Arto

doi:10.1248/yakushi.12-00234-3

Cited by 16 publications

(10 citation statements)

References 11 publications

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“…In recent years, different topical liposomes have been developed to deliver drugs into the posterior segment of the eye [23][24][25][26][27][28][29][30][31]. For example, fluorescent molecules like 5(6)-carboxyfluorescein and coumarin-6 [23,25,29,30], drugs such as edaravone and diclofenac [26,27], and biomolecules such as nucleic acids [28,31] and bevacizumab (a monoclonal antibody against vascular endothelial growth factor A) [24] have been released into the vitreous body and retina by liposomes.…”

Section: Introductionmentioning

confidence: 99%

Safety and Tolerability of Topical Ophthalmic Triamcinolone Acetonide-Loaded Liposomes Formulation and Evaluation of Its Biologic Activity in Patients with Diabetic Macular Edema

et al. 2021

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Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA-loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled on the ocular surface. To evaluate the safety, tolerability, and biological activity of TALF, an animal study and a phase I clinical assay were performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biological activity of the formulation. No inflammation, lens opacity, swelling, or increase in intraocular pressure were recorded after the instillation of TALF in any of the animal or clinical studies. Mainly, mild and transient adverse events such as dry eye and burning were reported. TALF significantly improves visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biological activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroid IVTs and their associated hazards.

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Section: Introductionmentioning

confidence: 99%

Safety and Tolerability of Topical Ophthalmic Triamcinolone Acetonide-Loaded Liposomes Formulation and Evaluation of Its Biologic Activity in Patients with Diabetic Macular Edema

et al. 2021

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“…Liposomes are an attractive option for nonviral gene therapy. 35 Liposomes, vesicles formed by phospholipid bilayers, are biocompatible and can be tailored for various sizes, release rates, hydrophilicity, and lipophilicity. 36 Furthermore, the lipid bilayer of liposomes can integrate and pass through cell membranes without the need for electroporation.…”

Section: Suprachoroidal Nonviral Gene Deliverymentioning

confidence: 99%

Suprachoroidal Delivery of Viral and Nonviral Gene Therapy for Retinal Diseases

Kansara

Muya

Wan

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

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Retinal gene therapy is a rapidly growing field with numerous clinical trials underway, and route of delivery is a critical contributor to its success. Subretinal administration, which involves pars plana vitrectomy in the operating room, offers targeted delivery to retinal-pigment epithelium cells and photoreceptors. Due to the immune-privileged nature of the subretinal space, the risk of an immune reaction against viral capsid antigens is minimized, an advantage of subretinal administration in patients with preexisting neutralizing antibodies. Intravitreal administration, with fewer procedure-related complications, is challenged by potential immune response and incomplete vector penetration through the internal limiting membrane. However, novel vectors, optimized by ''directed evolution'' may address these issues. Nonsurgical in-office suprachoroidal gene delivery offers the potential for greater surface-area coverage of the posterior segment compared to focal subretinal injection, and is not hindered by the internal limiting membrane. However, the vector must pass through multiple layers to reach the targeted retinal layers, and there is a risk of immune response. This review highlights recent developments, challenges, and future opportunities associated with viral and nonviral suprachoroidal gene delivery for the treatment of chorioretinal diseases. While ocular tolerability and short-term effectiveness of suprachoroidal gene delivery have been demonstrated in preclinical models, durability of gene expression, long-term safety, potential systemic exposure, and effective delivery to the macula require further exploration. Although the safety and efficacy of suprachoroidal gene delivery are yet to be proven in clinical trials, further optimization could facilitate nonsurgical in-office suprachoroidal gene therapy.

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“…Special mention is reserved for the study performed by Davis BM et al This group demonstrated that the topical instillation of eye drops containing annexin A5 associated with liposomes loaded with bevacizumab is able to deliver physiologically significant concentrations of this large therapeutic protein (monoclonal antibody against vascular endothelial growth factor A) into the posterior segment of the eye in animal models (rats and rabbits) [156]. Moreover, liposomes can release genetic material into the vitreous and the retina [160,163].…”

Section: Topical Liposomes For Drug Delivery Into the Posterior Segmementioning

confidence: 99%

“…[155][156][157][158][159][160][161][162][163].Breaking down the Barrier: Topical Liposomes as Nanocarriers for Drug Delivery… DOI: http://dx.doi.org/10.5772/intechopen.86601…”

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confidence: 99%

Breaking down the Barrier: Topical Liposomes as Nanocarriers for Drug Delivery into the Posterior Segment of the Eyeball

Santos¹,

Altamirano-Vallejo²,

Navarro-Partida³

et al. 2020

Role of Novel Drug Delivery Vehicles in Nanobiomedicine

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Topical instillation is the most widely preferred noninvasive route of drug administration to treat diseases affecting the anterior segment of the eye. Nonetheless, the ocular bioavailability for deeper ocular tissues is very low. Different routes of administration, such as intravitreal injections, periocular injections, and systemic administration, have been used to deliver drugs into the posterior segment ocular tissues. However, the presence of blood-retinal barriers (BRBs) makes systemic administration an impractical approach, whereas the drug delivery with the periocular administration route is compromised by ocular static and dynamic barriers. On the other hand, intravitreal injection, the most common and widely recommended route for drug administration to treat posterior ocular diseases, is related to several side effects such as endophthalmitis, hemorrhage, retinal detachment, and poor patient tolerance. Diverse strategies to overcome ocular barriers have been explored for topical drop formulations in order to deliver drugs into the posterior segment ocular tissues. In this chapter, we will review the promising topical nanocarriers for drug delivery into the posterior segment of the eye, emphasizing the use of liposomes for topical ophthalmic formulations targeting the vitreous cavity and the retina.

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Non-Invasive Ophthalmic Liposomes for Nucleic Acid Delivery to Posterior Segment of Eye

Cited by 16 publications

References 11 publications

Safety and Tolerability of Topical Ophthalmic Triamcinolone Acetonide-Loaded Liposomes Formulation and Evaluation of Its Biologic Activity in Patients with Diabetic Macular Edema

Safety and Tolerability of Topical Ophthalmic Triamcinolone Acetonide-Loaded Liposomes Formulation and Evaluation of Its Biologic Activity in Patients with Diabetic Macular Edema

Suprachoroidal Delivery of Viral and Nonviral Gene Therapy for Retinal Diseases

Breaking down the Barrier: Topical Liposomes as Nanocarriers for Drug Delivery into the Posterior Segment of the Eyeball

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