Development and in vivo evaluation of an implantable nano-enabled multipolymeric scaffold for the management of AIDS dementia complex (ADC).

This study reports the use of biocompatible and biodegradable polymers for the formulation and design of an implantable multipolymeric drug delivery device (MDDD) for the management of AIDS dementia complex (ADC), a debilitating condition affecting the cognitive, motor and behavioral systems in HIV+ individuals. A 3-factor Box-Behnken statistical design was employed for the optimization of nanoparticle and multipolymeric scaffold formulations. Fifteen formulations were generated using the Box-Behnken template, which were assessed for physicochemical and physicomechanical characterization. The optimised nanoparticle formulation yielded nanoparticles measuring 68.04nm in size and zeta potential (ZP) of -13.4mV was calculated for the colloidal system. In an attempt to further retard drug release and to formulate a device for implantation in the frontal lobe of the brain, nanoparticles were dispersed within a multipolymeric matrix. Matrix erosion was calculated at 28% for multipolymeric scaffold and a matrix resilience of 4.451% was observed 30 days post exposure to PBS, indicating slow degradation of the MDDD. In vivo studies showed 12.793ng/mL and 35.225ng/mL AZT level in plasma and CSF. In view of the physicomechanical properties, in vitro and in vivo drug release kinetics of MDDD makes it a potential candidate for the management of the ADC.

Carcinogenic nitrosamines in traditional beer as the cause of oesophageal squamous cell carcinoma in black South Africans.

BACKGROUND: Before the 1930s, squamous cell carcinoma (SCC) of the oesophagus was almost unknown among black South Africans. From the 1930s the annual frequency rose. A dietary cause was sought, the staple diet of black people having changed from sorghum to maize (corn), with traditional beer being brewed from maize. Carcinogenic N-nitrosamines in traditional beer were suggested as a cause of SCC of the oesophagus, with Fusarium moniliforme, a corn saprophyte, thought to play a role. OBJECTIVES: To confirm the presence of N-nitrosamines in traditional beer and demonstrate a mechanism for the oncogenesis of oesophageal carcinoma. METHODS: Analysis by high-performance liquid chromatography was conducted for the identification of nitrosamines in traditional beer samples, and molecular docking studies were employed to predict the affinity between N-nitrosamines and the S100A2 protein. RESULTS: Carcinogenic N-nitrosamines were identified in all six samples of traditional beer examined (N=18 analyses), and docking studies confirmed a high affinity of the nitrosamine N-nitrosopyrrolidone with the S100A2 protein. This may result in the altered expression of the S100A2 protein, leading to tumour progression and prognosis. CONCLUSION: It is suggested that carcinogenic N-nitrosamines in traditional beer are a major factor in the causation of SCC of the oesophagus in black South Africans. N-nitrosamines have been shown to produce cancer experimentally, but there has not been conclusive epidemiological evidence that N-nitrosamines are carcinogenic to humans. This study is the first to demonstrate the potential link between N-nitrosamines and a human tumour.

A review of topically administered mini-tablets for drug delivery to the anterior segment of the eye.

OBJECTIVES: The human eye is a unique and intricate structure which has made drug delivery to the eye a formidable undertaking. Anterior-segment eye diseases are ubiquitous, especially among elderly patients, and conventional eye drops, although a first-choice dosage form, are not always an efficient treatment option. The development of novel drug delivery systems for improved treatment is therefore imperative. KEY FINDINGS: In an attempt to circumvent the obstacles presented by the structure of the eye, advanced systems such as ocular mini-tablets have been developed. In this review, a concerted effort has been made to provide a detailed overview of topically administered ocular mini-tablets and other solid devices for drug delivery to the anterior segment of the eye. These mini-tablets have been shown in vitro and in vivo to have significant advantages in comparison with liquid preparations. This is a step toward attaining better patient convenience and compliance, which are critical factors. SUMMARY: Solid ophthalmic dosage forms have several advantages that can contribute to assisting with patient compliance and, ultimately, effective disease treatment. In addition to the challenges associated with topical ocular drug delivery, the shortcomings of conventional eye drops, advantages of mini-tablets, and improvements to date to these systems are discussed. The requirement for further advancements in the ocular field is also emphasized.

Integration of biosensors and drug delivery technologies for early detection and chronic management of illness.

Recent advances in biosensor design and sensing efficacy need to be amalgamated with research in responsive drug delivery systems for building superior health or illness regimes and ensuring good patient compliance. A variety of illnesses require continuous monitoring in order to have efficient illness intervention. Physicochemical changes in the body can signify the occurrence of an illness before it manifests. Even with the usage of sensors that allow diagnosis and prognosis of the illness, medical intervention still has its downfalls. Late detection of illness can reduce the efficacy of therapeutics. Furthermore, the conventional modes of treatment can cause side-effects such as tissue damage (chemotherapy and rhabdomyolysis) and induce other forms of illness (hepatotoxicity). The use of drug delivery systems enables the lowering of side-effects with subsequent improvement in patient compliance. Chronic illnesses require continuous monitoring and medical intervention for efficient treatment to be achieved. Therefore, designing a responsive system that will reciprocate to the physicochemical changes may offer superior therapeutic activity. In this respect, integration of biosensors and drug delivery is a proficient approach and requires designing an implantable system that has a closed loop system. This offers regulation of the changes by means of releasing a therapeutic agent whenever illness biomarkers prevail. Proper selection of biomarkers is vital as this is key for diagnosis and a stimulation factor for responsive drug delivery. By detecting an illness before it manifests by means of biomarkers levels, therapeutic dosing would relate to the severity of such changes. In this review various biosensors and drug delivery systems are discussed in order to assess the challenges and future perspectives of integrating biosensors and drug delivery systems for detection and management of chronic illness.