Tuesday, May 30, 2006

The problem of catheter infections plus advances in the treatment of colorectal cancer

DailyUpdates 30th May: As the drug discovery sector returns after various public holidays around the world, we too return with another edition of DailyUpdates. Amongst the 60 or so features today, we highlight work at Kane Biotech conducted in an attempt to reduce the major problem of catheter infection, plus news on the development of a liposomal candidate designed to deliver the active metabolite of Camptosar to colorectal cancer tumors. Summaries of this work are provided below - today's edition in its entirety can be accessed here

Attacking biofilms to reduce the problem of catheter infections:
Urinary tract infections are the second-most common type of bacterial infection, after those of the respiratory tract, with more than 35 million medically treated infections across the seven major markets each year (2003 figures according to Urinary Tract Infections - Ciprofloxacin Leads the Way). This translated into sales in excess of $1.1billion across key markets. The formation of bacterial biofilms on urinary tract catheters represents one segment of the urinary tract infections market. Biofilms, which contribute to 80% of all human bacterial infections, are matrix-enclosed microbial populations adherent to each other and/or surfaces or interfaces. Biofilms are highly resistant to various anti-infective strategies and biofilm colonies on urinary catheters can be more than 1,000 times more resistant to antibiotics than their planktonic counterparts. Foley catheter infections lead to approximately 900,000 noscomial urinary track infections annually in the US at a cost of $0.65-3.5 billion. In addition to the financial burden, biofilm formation frequently leads to the infection of surrounding tissue and often requires removal of the catheter subjecting the patient to discomfort. Today’s featured study reports on work conducted at Kane Biotech which has led to the development of an antibiofilm composition comprising an N-acetyl-d-glucosamine-1-phosphate acetyltransferase (GlmU) inhibitor and protamine sulfate, a cationic polypeptide. This composition demonstrated antimicrobial efficacy against a range of microbes and represents a licensing opportunity. Since biofilm formation represents a problem which extends past the urinary tract such technology is likely to have wide-ranging relevance in infectious diseases including for example vascular cannula infections, a serious problem in the ICU setting.

Improved treatments of colorectal cancer on the horizon: Drug delivery remains a challenge in management of cancer. One area that is being extensively researched in an attempt to overcome this problem is the development of liposome technology. Liposomes are artificial lipid micelles used to transport active agents to their site of action. Such agents can range from steroids for the treatment of inflammatory disease to cytotoxic agents. One good example of this technology is pegylated liposomal doxorubicin, marketed as Caelyx in the UK and as Doxil in the USA . Liposome delivery affords tumor targeting and reduced toxicity. The administration of poorly soluble chemotherapeutics can also be improved by liposome technology (see Drug Delivery in Cancer - technologies, markets and companies). Today’s featured press release comes from NeoPharm who announce that patient enrollment has commenced in a multi-center Phase II clinical trial of LE-SN38 in the treatment of patients with metastatic colorectal cancer. LE-SN38 is NeoPharm's NeoLipid liposomal formulation of SN-38, the active metabolite of irinotecan (Camptosar). Camptosar is converted into SN-38 in colorectal cancer cells at different rates in different patients, and this variability in conversion rates may result in suboptimal treatment with Camptosar. Although SN-38 is highly active, its poor solubility restricts its direct delivery. Liposomal SN-38 should reduce this limitation and be of considerable benefit in the treatment of colorectal cancer.


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