Targeted drug delivery vehicles mediated by nanocarriers and aptamers for posterior eye disease therapeutics: barriers, recent advances and potential opportunities

Nanomedicine and aptamer have excellent potential in giving play to passive and active targeting respectively, which are considered to be effective strategies in the retro-ocular drug delivery system. The presence of closely adjoined tissue structures in the eye makes it difficult to administer the drug in the posterior segment of the eye. The application of nanomedicine could represent a new avenue for the treatment, since it could improve penetration, achieve targeted release, and improve bioavailability. Additionally, a novel type of targeted molecule aptamer with identical objective was proposed. As an emerging molecule, aptamer shows the advantages of penetration, non-toxicity, and high biocompatibility, which make it suitable for ocular drug administration. The purpose of this paper is to summarize the recent studies on the effectiveness of nanoparticles as a drug delivery to the posterior segment of the eye. This paper also creatively looks forward to the possibility of the combined application of nanocarriers and aptamers as a new method of targeted drug delivery system in the field of post-ophthalmic therapy.

Critical evaluation of the off-label indication and of the risks associated to the use of multi-dose vials on the treatment of age-related macular degeneration

Age-related macular degeneration (AMD) is an ocular inflammatory diseases treated mainly by means of a bevacizumab (Avastin®) or ranibizumab (Lucentis®) intravitreal injection. Among these drugs, only ranibizumab has a specific therapeutic indication for AMD. Considering that, the off-label use on ophthalmic therapy seems to become a rule when it should be an exception. Furthermore, bevacizumab presentation consists of multi-dose vials although it does not contain preservatives in its formula. The current literature review aimed at assessing the risks for the patient related to the use of off-label indication and multi-dose vials on AMD treatment. Considering this, the proposal related to the Brazilian Public Consultation no.10, dated September 12, 2012, which proposes the Clinical Protocol and Therapeutic Guidelines for AMD treatment, was evaluated. This systematic review allowed to conclude that the bevacizumab off-label indication results in increased risks for the patient when compared to the product with specific therapeutic indication for AMD treatment (ranibizumab), especially referring to the significant raise in the adverse events. The risks for the patient related to the multi-dose vial use, referring to the microbiological stability and dose precision, were also made clear.

An Insight into Ophthalmic Drug Delivery System

Promising management of eye ailments take off effective concentration of drug at the eye for sufficient period of time. Dosage forms are administered directly to eye for localized ophthalmic therapy. Most of the treatments call for the topical administration of ophthalmic active drugs to the tissues around the ocular cavity. Conventional ophthalmic drug delivery systems including eye drops, ophthalmic ointments, are no longer sufficient to encounter eye diseases. This article reviews the constraints with conventional ocular therapy and explores various novel approaches like in-situ gel, ocular films or ocuserts, nanosuspension, collagen shields, latex systems, nanoparticles, liposomes, niosomes, iontophorosis, eye implants, etc to improve the ophthalmic bioavailability of drugs to the anterior chamber of the eye.

Chemoreduction and Local Ophthalmic Therapy for Intraocular Retinoblastoma

PURPOSE: To study the effectiveness of combined systemic chemotherapy and local ophthalmic therapy for retinoblastoma with the goal of avoiding enucleation and external-beam radiation therapy (EBRT). PATIENTS AND METHODS: This was a prospective, nonrandomized, single-arm clinical trial. Seventy-five eyes were followed in 47 children. Patients were treated with a six-cycle protocol of vincristine, etoposide, and carboplatin. Most (83%) also received ophthalmic treatment (cryotherapy, laser photocoagulation, thermotherapy, or plaque radiation therapy) during and/or after the chemotherapy. RESULTS: With a median follow-up of 13 months, event-free survival was 74%, with an event defined as enucleation and/or EBRT. Six children required EBRT in seven eyes (9%); five required enucleation of one eye (7%); five required a combination of EBRT and enucleation in six eyes (8%). Reese-Ellsworth groups 1, 2, and 3 eyes had excellent results, with avoidance of EBRT or enucleation in all 39. Treatment of groups 4 and 5 was less successful, with 33% of six eyes and 53% of 30 eyes, respectively, requiring EBRT and/or enucleation. Toxicities from chemotherapy were mild and included cytopenias (89%), fever and neutropenia (28%), infection (9%), and gastrointestinal symptoms, dehydration, and vincristine neurotoxicity (40%). No patients developed a second malignancy, metastatic disease, renal disease, or ototoxicity. CONCLUSION: In retinoblastoma patients with Reese-Ellsworth eye groups 1, 2, or 3, systemic chemotherapy used with local ophthalmic therapies can eliminate the need for enucleation or EBRT without significant systemic toxicity. More effective therapy is required for Reese-Ellsworth eye groups 4 and 5.