Prospects of Delivering Natural Compounds by Polymer-Drug Conjugates in Cancer Therapeutics.

Synthetic chemotherapeutics have played a crucial role in minimizing mostly palliative symptoms associated with cancer; however, they have also created other problems such as system toxicity due to a lack of specificity. This has led to the development of polymer-drug conjugates amongst other novel drug delivery systems. Most of the formulations designed using delivery systems consist of synthetic drugs and face issues such as drug resistance, which has already rendered drugs such as antibiotics ineffective. This is further exacerbated by toxicity due to the long-term use. Given these problems and the fact that conjugation of synthetic compounds to polymers has been relatively slow with no formulation on the market after a decade of extensive studies, the focus has shifted to using this platform with medicinal plant extracts to improve solubility, specificity and increase drug release of medicinal and herbal bioactives. In recent years, various plant extracts such as flavonoids, tannins and terpenoids have been studied extensively using this approach. The success of formulations developed using novel drug-delivery systems is highly dependent on the tumour microenvironment especially on the enhanced permeability and retention effect. As a result, the compromised lymphatic network and 'leaky' vasculature exhibited by tumour cells act as a guiding principle in the delivery of these formulations. This review focuses on the state of the polymer-drug conjugates and their exploration with natural compounds, the progress and difficulties thus far, and future directions concerning cancer treatment.

Transient Expression of Interleukin-21 in the Second Hit of Acute Pancreatitis May Potentiate Immune Paresis in Severe Acute Pancreatitis.

OBJECTIVES: Interleukin-21 (IL-21) is a cytokine associated with tissue inflammation, autoimmune and infectious diseases. Organ dysfunction and death can occur in patients with acute pancreatitis (AP) in two distinct clinical phases. Initially, a systemic inflammatory response syndrome may be followed by systemic sepsis from infected pancreatic necrosis, known as the "second hit." The expression and possible role of IL-21 in AP has not been established. METHODS: Thirty-six patients with mild, moderate, and severe AP (SAP) were enrolled. Peripheral blood samples of patients were drawn on days 7, 9, 11, and 13. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed to determine the expression and concentration of IL-21. RESULTS: Interleukin-21 mRNA levels increased significantly at day 9 in severe (P = 0.002) pancreatitis compared with both the mild and control patient groups. At the protein level, IL-21 was elevated in SAP patients compared with those with mild pancreatitis, although this was not significant. Furthermore, day 9 IL-21 was elevated in septic SAP patients and patients with pancreatic necrosis. CONCLUSIONS: Interleukin-21 is transiently elevated in SAP compared with the mild/moderate group, and hence IL-21 may contribute to the immune imbalance that occurs in AP.