Recent Patents on Drug Delivery & Formulation 2010, 4, 153-173 153 1872-2113/10 $100.00+.00 © 2010 Bentham Science Publishers Ltd. Microbial Colonization of Medical Devices and Novel Preventive Strategies Tamilvanan Shunmugaperumal* International Medical University (IMU) SDN BHD, No. 126, Jalan 19/155B, Bukit Jalil, Kuala Lumpur 57000, Malaysia Received: January 12, 2010; Accepted: February 22, 2010; Revised: February 25, 2010 Abstract: Upon implantation or insertion into patient's body for exerting the intended purpose like salvage of normal functions of vital organs, the medical devices are unfortunately becoming the sites of competition between host cell integration and microbial adhesion. Moreover, since there is an increased use of implanted medical devices, the incidence of biofilm-and medical devices-related nosocomial infections is also increasing progressively. To control microbial colonization and subsequent biofilm formation of the medical devices, different approaches either to enhance the efficiency of certain antimicrobial agents or to disrupt the basic physiology of the pathogenic microorganisms including novel small molecules and antipathogenic drugs are being explored. In addition, the various lipid-and polymer-based drug delivery carriers are also investigated for applying antibiofilm coating of the medical devices especially over catheters. The main intention of this review is therefore to summarize the major and/breakthrough inventions disclosed in patent literatures as well as in research papers related to microbial colonization of medical devices and novel preventive strategies. This review starts with an overview of the preventive strategies followed by a short description about the potential of different lipidic-and polymeric-drug delivery carriers in eradicating the biofilm-associated infections from the medical devices. Keywords: Catheters, colonization, implants, liposomes, microbial biofilm, medical devices, quorum sensing. INTRODUCTION The use of surgically implanted or non-surgically inser- ted medical devices has received more interest in modern medical practices. This is due to a result of their beneficial effect on quality of life and in some circumstances, on patient survival rates. Upon implantation or insertion into patient's body for exerting the intended purpose like salvage of normal functions of vital organs, these medical devices are unfortunately becoming the sites of competition between host cell integration and microbial adhesion. Moreover, the non-shedding surfaces of these devices provide ideal substrata for colonization by biofilm-forming microbes. Hence, the incidence of biofilm-and medical devices-related nosocomial infections is also increasing progressively. Example of medical devices that can be affected by biofilm- associated infections include central venous catheters, heart valves, ventricular assist devices, coronary stents, neuro- surgical ventricular shunts, urological medical devices, implantable neurological stimulators, arthroprostheses, fracture-fixation devices, inflatable penile implants, breast implants, cochlear implants, intra-ocular lenses and dental implants. According to Donlan and Costerton [1], biofilm is defined as a microbially derived sessile community, charac- terized by cells that are attached to a substratum, interface, or to each other, are embedded in a matrix of extracellular Address correspondence to this author at the International Medical University (IMU) SDN BHD, No. 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia; Tel: +60-3- 2731 7484, Fax: +60-3-8656 7229; E-mail: tamilvanan2k@yahoo.com polymeric substance (EPS), and exhibit an altered phenotype with regard to growth, gene expression, and protein production. The formation of microbial consortium onto the surface of medical devices is a dynamic five-step process viz., surface conditioning, reversible attachment, irreversible attachment, colonization and detachment [2]. According to a patent [3], the (substrate) materials used to manufacture medical devices can be made with a variety of polymeric, ceramic and metallic materials, as well as combinations of two or more of the same (e.g. hybrid materials). Since the medical devices are routinely being made up of many different types of surfaces, the physicochemical charac- teristics of the materials play a major role to act as a substrate for microbial attachment and colonization. Clinical manifestations of device-related infections are very vulnerable which include life-threatening systemic infections and device malfunction that may require device removal, urological medical devices-crystalline encrustation and pain, increased morbidity and mortality, additional hospital cost to patient, blocking encrustation and mecha- nical failure or fracture, etc. Furthermore, a sequence of events that leads to the foreign body reaction following implantation of a medical device, prosthesis, or biomaterial is also presented in a review [4]. Therefore, owing to the problems associated with the use of medical devices, there is a clinical need for the development of novel materials [5] and novel coatings including diamond-like carbon (DLC) coatings over existing materials that will offer resistance to infection and encrustation [6-9], design of biomaterials with antimicrobial surfaces through some new surface modifi- cation techniques [10, 11], and finally the use of novel approaches to deliver antimicrobial agents for eradicating the biofilm consortia from the medical devices.