Eyesight is one of the most well-deserved blessings, amid all the five senses in the human body. It captures the raw signals from the outside world to create detailed visual images, granting the ability to witness and gain knowledge about the world. Eyes are exposed directly to the external environment; they are susceptible to the vicissitudes of diseases. The World Health Organization has predicted that the number of individuals affected by eye diseases will rise enormously in the next decades. However, the physical barriers of the eyes and the problems associated with conventional ocular formulations are significant challenges in ophthalmic drug development. This has generated the demand for a sustained ocular drug delivery system, which serves to deliver effective drug concentration at a reduced frequency for consistent therapeutic effect and better patient treatment adherence. Recent advancement in pharmaceutical dosage design has demonstrated that a stimuli-responsive in situ gel system exhibits the favorable characteristics for providing sustained ocular drug delivery and enhanced ocular bioavailability. Stimuli-responsive in situ gels undergo a phase transition (solution-gelation) in response to the ocular environmental temperature, pH, and ions. These stimuli transform the formulation into a gel at the cul de sac to overcome the shortcomings of conventional eye drops, such as rapid nasolacrimal drainage and short contact time with the ocular surface This review highlights the recent successful research outcomes of stimuli-responsive in situ gelling systems in treating in vivo models with glaucoma and various ocular infections. Additionally, it also presents the mechanism, recent development, and safety considerations of stimuli-sensitive in situ gel as the potential sustained ocular delivery system for treating common eye disorders.
Since the effects of once-daily antihypertensive (HT) medications are more pronounced within the first few hours of ingestion, evening administration of anti-HT medications can be a feasible treatment for nocturnal HT. However, no relevant meta-analysis has been conducted in patients with nocturnal HT. This meta-analysis included randomized controlled trials involving patients with elevated mean nocturnal blood pressure (BP) and compared evening anti-HT administration with morning administration. Multiple databases, including grey literature (e.g. clincialtrial.gov), were searched. Study selection and data extraction were conducted by two independent authors. Risk of bias assessment and overall quality of evidence were conducted using Cochrane risk-of-bias tool and GRADE by two independent authors. A total of 107 studies were included, 76 of which were investigated in China and had not been identified in previous reviews. Only one trial was ranked low risk-of-bias. Evening administration of anti-HT medications was effective in reducing nocturnal systolic BP (4.12-9.10 mmHg; I2 = 80.5-95.2%) and diastolic BP (3.38-5.87 mmHg; I2 = 87.4-95.6%). Subgroup analyses found that the effectiveness of evening administration was contributed by data from the Hermida group and China. Evening administration did not provide additional nocturnal/daytime/24-h BP reduction in non-Hermida/non-China studies (I2 = 0) and in meta-analyses that included studies with unclear or low risk of bias. The effectiveness of nocturnal BP reduction was similar across different types, doses, and half-lives of medications. Evening administration of anti-HT medications may reduce proteinuria, left ventricular hypertrophy (LVH), nondipping and morning surge. The overall quality of evidence was ranked as very low to low. Our results highlight the scarcity of low risk-of-bias studies and emphasize the need for such trials to evaluate the efficacy of evening dosing of anti-HT medications as a standard treatment for patients with nocturnal HT across diverse populations.