Recombinant protein polymers as carriers of chemotherapeutic agents.

Chemotherapy is the standard of care for the treatment of cancer and infectious diseases. However, its use is associated with severe toxicity and resistance arising mainly due to non-specificity, resulting in disease progression. The advancement in recombinant technology has led to the synthesis of genetically engineered protein polymers like Elastin-like polypeptide (ELP), Silk-like polypeptide (SLP), hybrid protein polymers with specific sequences to impart precisely controlled properties and to target proteins that have provided satisfactory preclinical outcomes. Such protein polymers have been exploited for the formulation and delivery of chemotherapeutics for biomedical applications. The use of such polymers has not only solved the limitation of conventional chemotherapy but has also improved the therapeutic index of typical drug delivery systems. This review, therefore, summarizes the development of such advanced recombinant protein polymers designed to deliver chemotherapeutics and also discusses the key challenges associated with their current usage and their application in the future.

A novel, minimally invasive implant to assist in repeated intraocular drug delivery.

The standard of care for posterior segment disorders such as wet age-related macular degeneration, diabetic macular oedema and retinal vascular occlusions is pharmacotherapy by intravitreal drug delivery. Since the therapeutic effect of these drugs lasts only around 4 to 8 weeks, repeated intravitreal injections are required. Pain is experienced by the patients during injection as the needle courses through the sclera and choroid. The current work describes the design and development of a novel anodized titanium alloy implant that allows for intravitreal injections through the implant so that the needle transverses only the conjunctiva, thus minimizing discomfort to the patient. Both ex-vivo testing of the implant in enucleated goat's eye as well as in-vivo validation in rabbit eyes was carried out. The implant was placed through pars plana via a minor surgical procedure and was sutured to the sclera and covered with conjunctiva. Subsequent intravitreal injections were administered under topical anaesthesia with a 30-gauge needle through the implant thus delivering the drug into the vitreous cavity. Repeated intravitreal injections were administered every 2 weeks via the implant for 3 months in 4 rabbits. Apart from cataract in 1 rabbit, no complications were observed. There was no evidence of intra-ocular inflammation or infection at final follow-up. Histopathological analysis did not reveal any inflammation or necrosis around the area of implant. The implants were subsequently removed at 5 months and scleral wound was closed with a single suture. The sclera and overlying conjunctiva healed well and no intraocular complications were observed after removal.