Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review.

Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD.

Drug delivery systems to prevent peritoneal metastasis after surgery of digestives or ovarian carcinoma: A review.

Peritoneum represents a frequent site of metastasis especially for digestive and ovarian primary cancers. The conventional approach to treat peritoneal metastasis consists in systemic chemotherapy, but the median survival associated is only a few months. Recent therapeutic developments result in an aggressive strategy associating cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC). However, a recent study failed to show an improvement in the overall survival and relapse free survival of this combo in comparison to CRS alone. Confronted to a lack of guidelines, several drug delivery systems (DDS) had been developed and tested in animal models to offer an effective easy-to-use solution for surgeons to prevent peritoneal metastasis. In this work, we reviewed most of the strategies used to treat peritoneal metastasis (PM) from digestive or ovarian origin and concentrated on 3 different DDS strategies: particulates DDS, non particulates DDS (including implants, films and gels) and combination of both (in particular hydrogels loaded with particles).

Thermosensitive hydrogels for local delivery of 5-fluorouracil as neoadjuvant or adjuvant therapy in colorectal cancer.

Spurred by high risk for local tumor recurrence and non-specific toxicity of systemic chemotherapy, clinicians have recently granted a growing interest to locoregional therapeutic strategies. In this perspective, we recently developed a multipurpose thermosensitive hydrogel based on reversible thermogelling properties of poloxamers P407 and P188, a bioadhesive excipient and antineoplastic effect of 5-fluorouracil (5-FU) for the local treatment of colorectal cancer (CRC) in ectopic CT26 murine models. Antitumor efficacy was assessed in mice following intratumoral (IT) injection mimicking neoadjuvant therapy and subcutaneous (SC) application after tumor excision simulating adjuvant therapy. Rheological characterization disclosed that P407/P188/alginate 20/2/1% w/v thermosensitive hydrogel is an injectable free-flowing solution at ambient temperature that undergoes a SOL-GEL transition at 26.0 °C ± 0.6 °C and thereby forms in situ a non-flowing gel at physiological temperature. The generated gel presented an elastic behavior and responded according to a shear-thinning fluid upon shear rate. Although delayed by the addition of alginate 1% w/v, 5-FU is released mainly by diffusion mechanism. The local delivery of 5-FU from P407/P188/alginate/5-FU 20/2/1/0.5% w/v hydrogel in the preclinical tumor models led to a significant tumor growth delay. These results demonstrated that poloxamer-based thermosensitive hydrogels provide a simple and efficient means for local chemotherapeutics delivery.