Marine Biomaterials for Drug Delivery Applications

Introduction
Marine ecosystem is the largest ecosystem on the planet. It is estimated that 2.2 million different kind of species are present in marine environment though 91 per cent of them are still await description. Marine species are classified into six kingdoms, bacteria, protozoans, chromists, fungi, plats and animals. Marine species are very uniquely produced from the exposure to exceptionally different oceanic environmental conditions. While it is true that a wide range of marine species are limited and protected, similarly there are also a variety of materials that are readily available and abundant and have yet to be exploited for their possible use. Materials and natural design of marine organisms have been instrumental to introduce the simplest remedies to vital problems in regenerative medicine, providing frameworks and highly accessible sources of osteopromotive analogues, nanofibers, micro and macrospheres and mineralising proteins. Studies show that marine polymers such as polysaccharides have substantial biological properties that could be used as anti-inflammation, antimicrobial, anticancer and for osteoporosis treatment. Marine derived collagen has also been extensively studied for different applications in tissue engineering. Marine species, such as corals, seashells and nacres, attract special interest in bioceramics field for bone graft, bone cements and drug delivery applications. Most of the marine structures are made up of pure calcium carbonate (calcite or aragonite) with a very small amount of an organic matrix.

The need for drug delivery devices
Current increases in the ageing population and increased longevity due to medical advances in many developed countries has led to a rise in the number of Musculoskeletal Disorders (MSDs). The number of medications to prevent and treat these diseases has also expanded in recent times due to scientific advances. The development of new drugs and active substances allows treatment of some of these diseases in very early stages. The key issue that has been explored widely in recent times with regards to these treatments is the ability to direct drugs to specific organs and musculo-skeletal sites. Most importantly, these treatments are designed to be able to effect locally when required. They are required to control the release rate of the drugs, in order to maintain a desired drug concentration levels without reaching to a toxic level or dropping below a minimum effective level. Drug delivery technology presents an interesting interdisciplinary challenge for pharmaceutical, chemical engineering, biomaterials and medical communities. In general, a biomaterial that will act as a drug carrier must have the ability to incorporate a drug, to retain it in a specific site, and to deliver it progressively with time to the surrounding tissues. Furthermore, it would be advantageous if the material is injectable or alternatively coatable on an implant and most importantly biodegradable.

Marine materials
Most marine structures are composed of calcium carbonate (aragonite or calcite) and can be easily converted into calcium phosphate materials by chemical exchange. The most common method of conversion is by hydrothermal exchange, which requires specialised equipment and long processing. Marine structures such as corals, seashells can be converted to Hydroxyapatite (HAp), or Calcium phosphate such as Tricalcium Phosphate (TCP). Hydrothermal conversion of marine structures to calcium phosphates did not change the original untransformed structure making it available for adsorption of drug compounds and to allow new bone cell penetration into the micropores. This was demonstrated in animal trials. Constructs that are generated in this manner provide many distinct advantages for tissue engineering as a physical template and devices for controlled release of BMP, Water-Soluble Proteins (WSP), genes and growth factors.

It has been reported that calcium phosphate bone substitutes derived from mixed hydroxyapatite and β tricalcium phosphate (β-TCP) are the most promising materials for bone drug delivery systems. During the last decade there have been several studies on both commercial and experimental calcium phosphate drug carriers. Major attention has been focused on the delivery of antibiotics, due to their wide areas of applications as prevention against infection during surgical interventions or in general in the treatment of bone infections. Ceramics and other materials have been proposed in the past, but it is difficult to form an appropriate shape with adequate micro porosity in order to be fitted into any type of shape and size of bone defect. The treatment of bone infection remains difficult because of problems with local penetration of systemically administered antibiotic. Furthermore, bacteria adhere to bone matrix and orthopaedic implants, eluding host defences by developing a biofilm or acquiring a very slow metabolic rate. Effective treatment against infection may be possible by killing the bacteria during the early stages of colonisation, followed by the continuous long time steady state delivery of appropriate amounts of antibiotics. Better approach would be combining marine structures capable of uptake and release bioactive clinical agent with biodegradable polymers to form biocomposites. Researches have revealed the excellent control and release of antibiotic from these devices. For most controlled release systems, the loaded dosages are usually high, and therefore the systemic exposure of antibiotic in blood and urine is the major safety concern. Usage of marine materials has an advantages of not only control the release of drug but also capable of releasing of key minerals such as Ca2+ and PO42- to support bone repair and regeneration.

Concluding remarks
The use of marine materials as drug delivery devices addresses a significant problem of biocompatibility of synthetic materials and the cost associated with their use. Marine materials can replace most the synthetic materials in drug delivery applications with improved therapeutic efficacy of drug for targeted and locally release. It is also easier to manipulate their properties by combining with other materials such as biodegradable polymer to achieve a certain applications. The release studies from marine materials further showed the ability of these devices to control the release for a prolonged period of time. Depending on the degree of clinical dosage required, the devices developed from marine materials could be tuned to release the drug in both short and prolonged periods of time. In addition to the therapeutic effect of the drugs, the use of marine derived HAp with drugs has the advantage of improving the bone-regenerative effect, due to local Ca2+ and PO42- ion release. Marine structures based on calcium carbonate can be easily converted to calcium phosphates for controlled-release devices in medical applications.