Recent Patents on Drug Delivery & Formulation - Volume 2, Issue 1, 2008

There are three main routes for delivery of drugs to the eye: topical, systemic and intra-ocular injection. Controlled delivery systems, such as ocular inserts, minitablets and disposable lenses, can be applied to the exterior surface of the eye for treatment of conditions affecting the anterior segment of the eye. Extended residence times following topical application have the potential to improve bioavailability of the administered drug and additionally a range of strategies has been tested to improve penetration including cyclodextrins, liposomes and nanoparticles. The first part of this review will focus on recent patent filings in this area. The second part of the review reports on drug delivery strategies for treatment of diseases of the posterior segment of the eye. The development of therapeutic agents that require repeated, long-term administration is a driver for the development of sustained-release drug delivery systems to result in less frequent dosing and less invasive techniques. This review article focuses on recently patented applications (from March 2004 to present) of drug delivery systems for ocular delivery.

Although the formulation of effective topical drug delivery system is one of the most sophisticated pharmaceutical preparations, it has attracted researchers due to many medical advantages associated with it. Topical drug delivery systems can act superficially on skin surface, locally in dermal layer of the skin or transdermally to provide successful delivery of drug molecules to the systemic circulation avoiding the traditional problems and limitations of conventional routes of drug delivery. Many novel formulations have been utilized topically to enhance either permeability or drug targeting to a specific layer of the skin such as Liposomes, ethosomes, transfersomes, niosomes and catezomes. The main problem with all of these formulations is that there is no distinct barrier between the targeting and localization action to a certain layer of the skin and the transdermal action to the circulation of these preparations. Any minimal change in the formulation could transform it from a local targeting preparation to a systemic one. This article deals with the innovations pertaining to the use of various types of liposomal preparations and liposomal like preparations for topical drug delivery and the patents associated with it.

Regenerative medicine requires the coordinated rebuilding of tissue and preservation of normal physiologic function. Cellular therapy incorporating tissue engineering principals has been among the most effective therapies, due to specific interactions between materials, cells, factors, and ligands that have been delineated over the last 5 decades. The current generation of these modalities incorporates the ability to control integration in vivo in a time- and space-dependent fashion. Hydrogels have been used as biofunctional vehicles for the introduction of these cell-based systems, and new techniques allow for the control of cell adhesion, proliferation, differentiation, and other biologic functions in vivo. With these more robust methods in place, and the ability to scale up and manufacture clinical materials, additional innovations have evolved that allow for ectopic or orthotopic administration of cellular therapies to treat disorders that have previously seen limited therapeutic promise due to inability to provide time-matched therapy. As such, critical discoveries have gained a unique niche portfolio of novel patents, accounting for a large portion of those newly filed in the field of biotechnology. These include the novel hydrogel compositions engineered by David Mooney and his colleagues, various tissue bulking and reconstructive applications invented by Hubbell and others, and other important patents in this field. The inventions described here provide insight into important aspects of this overall movement, and demonstrate significant immediate clinical utility in a variety of indications.

The treatment of brain disorders is the greatest challenge because of a variety of formidable obstacles in effective drug delivery and maintaining therapeutic concentrations in the brain for a prolonged period. The brain is a delicate organ, and evolution built very efficient ways to protect it. The same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Approximately, 100% of large molecule drugs and >98% of small molecule drugs do not cross the blood-brain barrier (BBB). Many advanced and effective approaches to brain delivery of drugs have emerged in recent years. Intranasal drug delivery is one of the important delivery options for brain targeting, as the brain and nose compartments are connected to each other via the olfactory/trigeminal route and via peripheral circulation. Realization of nose to brain transport and the therapeutic viability of this route can be traced from the ancient times and has been investigated for rapid and effective transport in the last two decades. Many patents have been filed in recent past, claiming enhanced delivery of intranasally administered therapeutics to the brain via olfactory/trigeminal neural pathways, use of novel devices for targeted delivery to olfactory region etc. Various models have been designed and studied by scientists to establish the qualitative and quantitative transport through nasal mucosa to brain. The development of nasal drug products for brain targeting is still faced with enormous challenges. A better understanding in terms of properties of the drug candidate, nose to brain transport mechanism, and transport to and within the brain is of utmost importance. A critical review of recent patents claiming different approaches for enhanced brain delivery through the nasal route will help in determining the focus of this promising area of research.

Skin forms a protective barrier to the entry of foreign molecules, especially water soluble compounds. Iontophoresis, one of the promising approaches to deliver water soluble drugs through the skin, has already been approved by FDA to deliver lidocaine and fentanyl. Iontophoresis involves application of current (< 0.5 mA/cm2) to push charged molecules into, or across the body tissue and offers programmable delivery. This technique encompasses various fields such as developing a device, sophistication of the device, electrode design, electronics and formulation. In addition, combination strategies with other enhancement techniques, is also gaining importance. The focus of this review is on the latest developments in the field of iontophoresis including trends in device development, electrode design, formulation and therapeutic applications as described in the patent literature.

The application of electroporation to enhance transdermal delivery has opened up a new possibility to introduce larger molecules such as peptide hormones and vaccines as well as minigenes and RNAi etc. through the transdermal route. Many devices have been developed to deliver the pulse electric field needed to permeate the skin. These devices include both non-puncturing surface electrodes as well as puncturing electrodes of different geometrical arrangements. The latter type uses electroporation only to increase uptake of molecules injected through the puncturing electrode or syringe. Different electroporation protocols have been developed to maximize transport, uptake and minimizing pain. Synergistic effect of chemical enhancers and physical (sonic, vibrational and thermal) treatments are used to enhance the transport. This article reviews the patents pertaining to the instrumentation as well as application protocols of transdermal delivery, uptake enhancement and interstitial fluid sampling by electroporation.

The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in the current manuscript.

DNA vaccination (or genetic immunization) strategies provide important opportunities for improving immunization, since both humoral and cell-mediated responses are induced. The use of genetic vaccines for inducing immunity to infectious agents can eliminate or significantly alleviate the pathology associated with a broad range of infections. A requirement for efficient DNA vaccination is the development of gene delivery systems capable of overcoming barriers to gene transfection. Compared to viral systems, nonviral systems are considered to be safe, cheap, multiple delivery is possible and able to deliver larger pieces of DNA. Also, these nanocarriers avoid DNA degradation and facilitate targeted delivery to antigen presenting cells. This review describes the potential of non-viral nanocarrier construct(s) in genetic immunization. Issued patents in the field were retrieved from the US patent database. Various carrier systems used to deliver plasmid DNA were reviewed in detail.

For the past few decades, there has been a considerable research interest in the area of drug delivery using particulate delivery systems as carriers for bioactive agents. Until now several reviews have been compiled on the nanoparticulate system concentrating on the various research works but there is no review, which compiles patents available for the nanoparticulate systems. Particulate systems like nanoparticles have been used as a physical approach to alter and improve the pharmacokinetic and pharmacodynamic properties of various types of drug molecules. A review on patents related to the nanoparticulate drug delivery systems has been prepared to summarize patents reported for the methods of preparation, applications in therapies and drug delivery. The status of patents for oral, topical and parenteral delivery has been discussed and the commercialized technology of nanoparticles for medical application has also been compiled.

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