Recent Patents on Biomedical Engineering (Discontinued) - Volume 5, Issue 1, 2012

We would like to thank the guest editors Drs. Sirinrath Sirivisoot, Rajesh Pareta and Thomas J. Webster for bring us the special issue focusing on novel nano-drug delivery systems and nanomaterials for treatments of major human diseases. Applications to several human diseases were reviewed, which include cardiovascular diseases (David A. Stout and Thomas J. Webster), diabetes (Rajesh A. Pareta), bone and cartilage regeneration (Jaclyn Lock and Huinan Liu), arthritis (Sang-Hyug Park, et al.), nerve regeneration (Justin M. Saul and James B. Clarke), and glaucoma, age related macular degeneration and uveitis (Aswani Dutt Vadlapudi et al.). In addition, novel concepts and technologies were reviewed and discussed including triggerable drug delivery systems, novel liposome formulations, nano-phase hydroxyapatite, multi-functional nano-particles and electrospinning technology. The broad coverage of the topics will attract broad readership and sustain the success of the journal. We would also like to thank the Editorial Board Members of the journal for their continued support. We would also like to thank Ms. Mehwish Akhter in Bentham Science Publishers her dedication and assistance during the editorial and publication processes.

Nanotechnology has drawn much attention in the field of implantable drug and gene delivery devices to treat various diseases worldwide. Control of the molecular assembly of materials at the nanoscale offers many advantages to selectively target diseases and locally release drugs leading to maximum therapeutic efficacy with low systemic toxicity. It has become increasing apparent that every individual responds differently to implanted medical devices and disease treatments. Yet, we continue to prescribe the same implants and treatments regardless of the inherent variations in immune systems. Nanotechnology could provide a way to match an individual's own immune system by developing devices that can simultaneously detect health problems and respond immediately to correct such health problems. Furthermore, such nano drug delivery systems can be controlled externally to release drugs only when required. Nanomaterials are small enough to enter cells and respond to external stimuli (like magnetic, infrared wavelengths, or conductivity) to both detect chemical imbalances and treat such imbalances through on-demand drug release. Although this is the next goal for nanotechnology in medicine, is it really that simple? Simplicity usually comes with great complications as Leonardo da Vinci (1452-1519) once said, “Simplicity is the ultimate sophistication”. The purpose of this special issue is to provide scientists and biomedical engineers both in research and industrial settings a platform where advanced in-situ drug delivery systems and smart implants are discussedin the context of nanotechnology. The drug delivery systems, nanomaterials, implants and nanotechnology are separately addressed first but the interrelationship of these systems can be clearly seen in the applications in health care today and becomes apparent among the contents of many topics covered in this issue. Enormous efforts have been made by different contributors to first provide an overview and then discuss the problem and finally, a nanotechnology-based treatment.....

With the advent of the nanotechnology era, one vital region with huge potential is the use of nano drug systems for cardiovascular applications. Nanotechnology offers a broad range of opportunities for improving drug delivery systems due to the fact that many biological components, like DNA, involve some sort of nano-dimensionality. In accordance with cardiovascular research and in contrast with conventional drugs, local nanotechnology drug delivery has the possibility to prevent restenosis-narrowing of a blood vessel which leads to restricted blood flow-while promoting endothelial cell and vascular healing. The advent of molecularly targeted medications has the ability to specifically bind to epitopes in the injured vascular tissue media and adventitia as well as unimpeded endothelial healing. The ability for nanotechnology to substantially improve and create novel new drug delivery systems for cardiovascular applications and associated patents will be reviewed herewith, with a special emphasis on stents, catheters and nanoparticle research and patents.

One current approach to the development of implantable drug/protein delivery systems utilizes a technique to produce electrospun fibrous structures, which have inherently high surface area to volume ratios, high interconnectivity, and structural morphologies similar to the extracellular matrix (ECM) of native tissues. The electrospinning technique is able to incorporate bioactive molecules into the fibers of these constructs to allow controlled release of the molecules over time. Thus, many synthetic polymers, natural materials, and their composites have been widely investigated as delivery vehicles for implantable drug/protein delivery systems. Recent patents for implantable drug/protein delivery systems fabricated using electrospinning technology, especially those designed for use in wound healing applications, coatings for medical devices, and tissue engineered scaffolds are summarized here. In addition, methods of reducing or eliminating the damaging effects of the organic solvents used in traditional electrospinning on the bioactivity of the encapsulated bioactive molecules are underlined, and these include blend electrospinning, emulsion electrospinning, coaxial electrospinning, and surface immobilization. In vitro cellular interactions of these electrospun fibers and clinically relevant animal experiments focusing on in vivo biocompatibility evaluations are further required for successful clinical translation.

With the development of biomedical techniques, a new generation of gene delivery systems were investigated, characterized and developed. Many of them were also filed as patents. Such advanced gene delivery techniques have greatly improved gene therapy from in vitro, in vivo to clinics. In this review, three most significant gene delivery systems (physical transfection techniques, virus based delivery vectors and chemically engineered delivery systems) will be studied and their advantages, limitations, patents and applications will be discussed.

Pharmaceutical development and therapeutic delivery as they pertain to nanomedicine predominantly involve the use of nanometer-sized (1-100nm) structures or complexes comprised of two or more constituents whose goal is to deliver a specific therapeutic to a targeted site for localized treatment. This illustrates one of the predominant underlying paradigms in nanomedicine: increased efficacy through targeted therapeutic delivery. With the advent of nanobiotechnology the precisely targeted delivery of pharmaceuticals and therapeutic agents can be achieved through a myriad of approaches which can be delineated by the level of bio-activity beginning with the nano-scale dispersion of pharmaceuticals. The primary constituent of nano-scale medicinal complexes is the pharmaceutical itself with the other contributing as a uni-functional “vehicle” for transport; a bi-functional natural or synthetic biodegradable vesicle or “shell” for encapsulation and timed release; or multi-functional components which include surface modification of said vesicle/shells for target- specific binding and/or conjugated with a contrast or fluorescent agent for imaging and/or tracking of drug mobility. This review will focus on cutting-edge nanostructured drug delivery systems for various biomedical applications. In addition, nanobiotechnology and its role in mediating tissue regeneration will be introduced. Recent awarded patents and their role in nanotechnology and nanomedicine development will be discussed.

Diabetes is one of the most prevalent diseases worldwide and is on the rise. At present, there are no life-long treatments to cure diabetes. Insulin therapy, while effective in short term leads to complicated secondary complications. Allogenic islet transplants are also not very effective and only works for few years. Lot of good research and patents has been presented for the development of bioartificial pancreas. The steps involve islet isolation, purification, microencapsulation and transplantation. Each of these processes is being refined continuously to achieve long-lasting transplants. In this review, we would mainly focus on the microencapsulation process and how it is being improved such that drugs like insulin, amylin and glucagon can be released by natural tissue in response to body feedback, which would lead to a normal life with no life long complications.

Current advancement in nanotechnology created novel solutions to improve drug delivery and enhance the efficacy of therapeutics for tissue regeneration and disease treatment. Nanomaterials can be designed and fabricated to have biomimetic characteristics and unique properties for controlling cellular functions (e.g. cell adhesion and stem cell differentiation) and delivering therapeutics more effectively. Different nanomaterials, including nanoparticles, nanofibers, nanospheres, and nanocomposites, are highlighted with key examples of in vitro and in vivo work. Specifically for bone regeneration, the use of nano-phase hydroxyapatite has received increased interest as it is naturally present in bone and has osteoinductive properties. Additionally, the use of nanotubes and nanofibers loaded with chondroprotective agents are utilized for cartilage regeneration. In addition to scaffold design, the use of different drugs (e.g. antibiotics, peptides, proteins, and growth factors) and their delivery rate are discussed. This review focuses on nanotechnology enabled innovative patents for targeted drug delivery to specific tissues (i.e. bone and cartilage) and prolonged multi-phase drug release.

In the last several decades liposome science has developed enormously. Many scientists have made significant discoveries and advancements in the clinical field using the unique properties of liposomes for drug delivery. These nanotechniques using liposomes have lead to a new era of nanomedicine especially in the diagnosis and therapeutics area. Aims of the present paper are to review the applications of liposomes in medicine related patents including the diagnosis and therapy for arthritis and discuss the potential of liposome based therapies.

The emergence of nanotechnology has made a major impact in medical device technology. Nanosized materials enable innovative solutions, including improvements in biocompatibility and advanced drug delivery systems. Through nanotechnology, one can design and incorporate “intelligent” materials and devices, which can respond to their surrounding environment or be externally triggered to improve their function. Various implantable medical devices for therapeutic delivery purposes are in demand to deliver medication at a specific site in patients and to control the release of drugs and genes by altering release times and/or rates to reach the maximum therapeutic benefit. In this review, the focus will be on triggered drug delivery through external stimulation and nanoscale delivery platforms for implants and prosthetics.

Injuries to the peripheral and central nervous system represent difficult physical challenges for those suffering from these injuries as well as a significant cost to the U.S. healthcare system. Treatment methods include electrical stimulation, improved rehabilitation techniques, cell therapies, and biomaterials. Biomaterial solutions to the challenges of nerve injury offer a potential long-term solution if used alone or in combination with other treatment modalities, and have therefore received considerable attention for product development. Controlled release of protein-based therapeutics such as growth factors is likely to be a critical design component to achieving long-term success with biomaterials. We consider the alternative approach of nucleic acid delivery through non-viral approaches as a means to achieve spatio-temporal control over growth factor delivery. We also describe promising aspects of non-viral delivery methods of antisense (e.g., siRNA) from biomaterials for nerve regeneration that could help to overcome the challenges of up-regulation of inhibitory molecules following injury.

Advancements in the field and rising interest among pharmaceutical researchers have led to the development of new molecules with enhanced therapeutic activity. Design of new drugs which can target a particular pathway and/or explore novel targets is of immense interest to ocular pharmacologists worldwide. Delivery of suitable pharmacologically active agents at proper dose (within the therapeutic window) to the target tissues without any toxicity to the healthy ocular tissues still remain an elusive task. Moreover, the presence of static and dynamic barriers to drug absorption including the corneal epithelium (lipophilic), corneal and scleral stroma (hydrophilic), conjunctival lymphatics, choroidal vasculature and the blood-ocular barriers also pose a significant challenge for achieving therapeutic drug concentrations at the target site. Although many agents are currently available, new compounds are being introduced for treating various ocular diseases. Deeper understanding of the etiology and complex mechanisms associated with the disease condition would aid in the development of potential therapeutic candidates. Novel small molecules as well as complex biotechnology derived macromolecules with superior efficacy, safety and tolerability are being developed. Therefore, this review article provides an overview of existing drugs, treatment options, advances in emerging therapeutics and related recent patents for the treatment of ocular disorders such as glaucoma, age related macular degeneration (AMD) and uveitis.

The patents annotated in this section have been selected from various patent databases. These recent patents are relevant to the articles published in this journal issue, categorized by medical imaging, bioinformatics, image processing, biomaterials, Pharmaceutical drugs, bioengineering, medical devices, design, biological devices, biomechanics & diagnostic devices related to biomedical engineering.