Recent Patents on Drug Delivery & Formulation - Volume 1, Issue 2, 2007

Immunotoxins and chimeric toxins are highly potent drugs designed for the treatment of cancer. Immunotoxins are composed of antibodies linked to a toxic substance. The antibodies enable the drug to bind specifically to distinct antigens on the tumor cell while the toxic moiety mediates cell death. Chimeric toxins are based on the same principle but contain other components for specific tumor cell targeting, e.g. cytokines or growth factors. The approval of the chimeric toxin denileukin diftitox (DAB389IL-2; Ontak) for the treatment of cutaneous T-cell lymphoma demonstrates the potential of immunotoxins and chimeric toxins for the treatment of cancer. New immunotoxins and possible treatment regimes are patented for commercial reasons before being published. Patents have become an indispensable requirement for pharmaceutical companies due to the high costs of drug development and clinical trials, allowing the protection of intellectual property and recovery of investments. This article reviews recent patents of immunotoxins and chimeric toxins. New agents are described and differences between certain patents are outlined to give an overview of the current situation of immunotoxins and chimeric toxins for the treatment of cancer.

Vaccines remain a key tool in the defence against major diseases. However, in the development of vaccines a trade off between safety and efficacy is required with newer vaccines, based on sub-unit proteins and peptides, displaying improved safety profiles yet suffering from low efficacy. Adjuvants can be employed to improve their potency, but currently there are only a limited number of adjuvant systems licensed for clinical use. Of the new adjuvants being investigated, particulate systems offer several advantages including: passive targeting to the antigen-presenting cells within the immune system, protection against adjuvant degradation, and ability for sustained antigen release. There has been a range of particulate vaccine delivery systems outlined in recent patents including polymerbased microspheres (which are generally more focused on the use of synthetic polymers, in particular the polyesters) and surfactant-based vesicles. Within these formulations, several patented systems are exploiting the use of cationic lipids which, despite their limitations in gene therapy, clearly offer strong potential as adjuvants. Within this review, the current range of particulate system technologies being investigated as potential adjuvants are discussed with regard to both their respective advantages and the potential hurdles which must be overcome for such systems to be converted into successful pharmaceutical products.

Nanotechnology is a rapidly evolving interdisciplinary field based on the manipulation of matter on a submicron scale, encompassing matter between 1 and 100 nanometers (nm). The currently registered nanotechnology patents comprise 35 countries being involved in the global distribution of these patents. Close to 3000 patents were issued in the USA since 1996 with the term ‘nano’ in the patents, with a considerable number having application in nanomedicine. The large majority of therapeutic patents are focused on drug delivery systems, highlighting an important application globally. Nanopharmaceutical patents are centered mainly on non-communicable diseases, with cancer receiving the greatest focus, followed by hepatitis. Drug delivery systems employing nanotechnology have the ability to allow superior drug absorption, controlled drug release and reduced side-effects, enhancing the effectiveness of existing drug delivery systems. Nanoparticle-based drug delivery systems may be among the first types of products to generate serious nanotechnology patent disputes as the multi-billion dollar pharmaceutical industry begins to adopt them. This review article aimed to locate patented nanopharmaceuticals in drug delivery online, employing pertinent key terms while searching the patent databases. Awarded and pending patents in the past 20 years pertaining to nanopharmaceutical or nano-enabled systems such as micelles, nanoemulsions, nanogels, liposomes, nanofibres, dendrimer technology and polymer therapeutics are presented in the review article, providing an overview of the diversity of the patent applications.

Rapid advances in drug discovery and development have spawned numerous innovative drug delivery approaches [1]. Although these efforts have primarily focused on optimizing the performance of drugs targeted for the current market, enhanced delivery of drugs may also result in the revitalization of marginally effective or failed formulations due to their original poor solubility. Plasma lipoproteins have long been considered as appropriate models for drug delivery vehicles, particularly because of their potential for transporting chemicals with low water solubility [2]. Additional features that render lipoproteins particularly suitable for drug delivery are their natural, bio-compatible components, their small size, the ability to deliver the drug itself rather than a prodrug or conjugate and their receptor mediated their uptake [3] or the uptake of their payload [4,5], particularly by cancer cells [6,7]. There has been increased activity in the patenting of lipoprotein type formulations in the last several years, primarily with the aim of developing enhanced drug delivery vehicles. This communication attempts to review the patenting activity in this area with particular focus on drug delivery and cancer chemotherapy.

The article critically discusses parenteral delivery of self-assembled lipid or amphiphile nanoparticles, in the form of aggregated clusters or particles (capsules). The end-product or drug form is for application by administration of the medicine active in encapsulated form. This is used for site-specific cell manipulation and clinical therapy and introduces this directly to the body via the systemic route. The technology discussed represents a platform formulation that can be modified for a range of specific cellular targets. The components of the nanoparticle are assembled piece-by-piece and this provides an element of design flexibility, with the core particle being built-up in a succession of layers to ensure circulatory longevity and storage stability. This strategy excludes a more generalised delivery and widespread lack of active targeting and thus low dosage rather than avoidance of target, which is at best detrimental and at worst catastrophic in terms of non-targeted cell death. However, in some cases such as the AmBisome nanoparticle this drug delivery approach can work. This “better focussing” is achieved by a dual use of i) biocompatible particle coating chemistry and a ii) cell-ligand imprinted nanoparticle surface that furnishes the engineered nanoparticle with a recognition element to form a complex but more efficacious dispersible fusogenic pro-drug moiety. Non-targeted delivery of drugs such as those commonly forming the basis of transdermal delivery have been generically based on topical or adhesive patch-based delivery (emulsions) systems. This procedure even with recent advancements and patents is customarily inefficient in dosage and payload delivery, inconsistent in terms of product potency and inflexible to further modification or purpose-related enhancement. The assembly and delivery methodologies discussed here take the new experimental medicine and review them in a more focused and purposeful therapy-constructed manner. It is the use of a smart platform technology that is responsible for increased efficacy when applied to the disorder of interest.

Ophthalmic drug delivery has long been a challenging task for pharmaceutical scientists seeking to alleviate various ocular diseases affecting the anterior and posterior segments. In order to deliver therapeutic agents to target tissues, the unique anatomical barriers of the eye must be circumvented effectively, without causing any patient discomfort or alteration in protective physiological mechanisms. This challenge is currently being met with the development of novel non-invasive delivery methods as well as improvements over existing techniques. Over the past decade many advanced technologies have been patented. Nevertheless a need for additional research and continuous innovation is still warranted. Patent literature is often essential for promoting new directions in research as well as for elucidating possibilities for future technologies. Hence, the aim of this review article is to discuss several recently filed patents on non-invasive modes of drug delivery to the ocular tissues. This review will also focus on the role of colloidal/particulate systems in ocular drug delivery and formulation. Recent patents filed on prodrugs as an efficient ophthalmic drug delivery mechanism also have been discussed. As a whole, this article is intended to provide a valuable insight into current trends in the field of ocular drug delivery and highlights advances made in patent literature.

Nanotechnology is the creation of functional materials, devices and systems through control of matter on the nanometer length scale, and exploitation of novel phenomena and properties (physical, chemical, biological, mechanical, electrical...) at that length scale. In the area of cosmetics and anti-aging, in particular, as well as in the pharmaceutical arena, nanotechnology has played an important role in delivering active ingredients to the skin, in both patch delivery and timed release application. Nanoparticles/nanospheres, nanospheres sounds like futuristic technology. The revolution they triggered is apparent from the fact that cosmetics are no longer visualized as products that cover up or camouflage imperfections in personal appearance. The latest trend in these products is to combine clinically proven ingredients with patented delivery systems and the aesthetics of fine cosmetics. Cosmeceutical products are those poised on the gap between cosmetic products that simply cleanse and beautify and pharmaceuticals that cure and heal. According to The Freedonia Group Inc. Cleveland Ohio, the demand for formulated appearance-enhancing products is projected to increase by more than 12% per year up to 2007 to reach $2.5bn, making cosmeceuticals one of the most dynamic sectors within the cosmetics and personal care markets. Cosmetic industries rank high among the nanotechnology patent holders in U.S.; L'Oreal which devotes about $600 million of its annual $17 billion revenues to research is the industry leader on nanopatents. This report directly addresses the science behind the use of nanotechnology for the development of cosmetics. Further, the products launched by various cosmetic giants will be discussed at length.

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