Recent Patents on Nanomedicine - Volume 2, Issue 2, 2012

One of the most challenging areas of pharmaceutical research is ocular drug delivery. The unique anatomy and physiology of the eye impedes drug permeation to deeper ocular tissues. Nanosized carrier systems such as nanoparticles, liposomes, suspensions, dendrimers, and nanomicelles are being explored for ocular drug delivery. In this review, we have focused on application of emerging nanomicellar carrier systems in ocular drug delivery. Nanomicelles are nanosized vesicular carriers formed from amphiphilic monomer units. Surfactant and polymeric micellar nanocarriers provide an amenable means to improve drug solubilization, develop clear aqueous formulations and deliver drugs to anterior and posterior ocular tissues. Nanomicelles due to their amphiphilic nature encapsulate hydrophobic drugs and aid in drug delivery. Various methods are employed to develop nanosized micellar formulations depending upon the physicochemical properties of the drug. Nanomicellar carriers appear to be promising vehicles with potential applications in ocular drug delivery. In this review, we attempted to discuss about the progress in ocular drug delivery research using nanomicelles as carriers from the published literature and issued patents. Also, with regards to ocular static and dynamic barriers which prevent drug permeation, a brief discussion about nanomicelles, types of nanomicelles, their methods of preparation and micellar strategy to overcome ocular barriers, delivering therapeutic levels of drugs to anterior and posterior ocular tissues are discussed.

Despite intense research efforts; effective delivery of drugs to the eye remains an enormous challenge. The eye is a unique organ with complex structure and functions. It is protected by static and dynamic barriers. Static barriers are formed by the relatively impermeable corneal layers, sclera, and retina, including blood aqueous and blood-retinal barriers, while dynamic barriers consist of choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution. Diseases affecting the eye such as cataract, glaucoma, wet and dry age-related macular degeneration, diabetic macular edema, proliferative vitreoretinopathy, uveitis, and cytomegalovirus retinitis, result in gradual loss of vision if left untreated. The design of an ideal drug delivery system requires thorough knowledge of the disease pathology and biochemical changes that occur at the molecular and cellular levels. Over the last decade, new treatment modalities comprised of nanocarriers are underway for optimizing the physicochemical properties of drug molecules and minimizing the barrier properties of the eye. Nanoparticles have the potential to improve pharmacokinetics of ophthalmic drugs by surpassing the blood-aqueous and blood-retinal barriers. This review provides comprehensive and updated information on ocular drug delivery, with special emphasis on research articles and patents that involve the use of polymeric nanoparticles in treatment of vision-threatening diseases.

The applications for ocular implants are as broad as the pathology of eye. The success of treating ophthalmologic disease will be enhanced by targeted and sustained drug delivery. The eye is a privileged site and has several mechanisms that protect it from the external environment. This same machinery that guards the eye, also hinders drug delivery. Recent advances in ocular implants are adapting these devices for the treatment eye diseases ranging from glaucoma to diabetic retinopathy. Advances in biodegradable polymers enable ocular implant to have dual mode drug release profiles to simultaneously deliver a loading dose and maintenance dose. We explore patents that adapt traditional medications to these advanced drug delivery systems for the continuous treatment of glaucoma and potentially promising therapies for the sustained delivery of small RNA interfering molecules to block gene expression in the eye. We also examine several issued patents and follow the preliminary findings in clinical trials. Together, these inventions mark the frontier of novel drug delivery systems and present a promising mode to adapt current therapies to new delivery systems for the treatment of chronic ocular disease.

Ocular iontophoresis is a time tested non-invasive tool for efficient delivery of drugs to both anterior and posterior segments of the eye. The review focuses on history of ocular iontophoresis, recent research developments on transcorneal/transscleral iontophoresis, prominent patents issued and filed on novel iontophoresis devices along with their treatment regimens. The review provides detailed information on development of ophthalmic iontophoretic devices, mode of action and the potential therapeutic applications. Further, the review discusses important clinical trials completed or inprogress on ocular iontophoresis targeting complex ocular disease states. A literary review of important developments in ophthalmic iontophoresis is expected to explore the growing prominence of this technique to effectively deliver drugs to both the superficial and inner ocular compartments targeting complex disease states as Glaucoma and Age Related Macular Degeneration.

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is found in the lipophilic extract of the rhizomes of turmeric (Curcuma longa). Numerous reports suggest that this natural compound possesses therapeutic benefit such as anti-tumor, anti-inflammatory and anti-oxidant activities. However, clinical tests have shown the bioavailability of conventional oral curcumin is low. Therefore the development of an efficient drug delivery system for curcumin is of considerable interest. Indeed, recent studies have demonstrated that a curcumin delivery system based on nanoscience and nanotechnology increases the therapeutic potential of this compound. Specifically, several nano-sized carriers such as phospholipid vesicles (liposomes), micelles, solid lipid nanoparticles, polymeric nanoparticles, emulsions, proteins and other molecular complexes have been developed for the efficient delivery of curcumin. Although curcumin itself is not a patentable compound, these formulations and the nanotechnology used to enhance the bioavailability of curcumin may lead to a patentable breakthrough for medical applications. This review focuses on curcumin nanoparticles for efficient delivery of the compound in biomedical applications.

Nanotechnology presents distinctive approaches to explore and manage a diversity of biological and medical processes. Nanomedicine is an emerging, recent technology that encompasses diagnostics and therapeutics at the nanoscale. With the rapid expansion of nanotechnology, the realization of important medical applications is rapidly being approached. In this review, we address the medical applications of a range of nanoparticles, including quantum dots, Polymeric, Gold, Superparamagnetic particles, dendrimers and carbon nanotubes. The nature and extent of current research carried out on these nanoscale particles in diagnostics will also be described. In this context the present review largely focuses on relevant patents in nanomedicine.

This is a review on nanotechnology in general and particularly it occupies different systems of ocular drug delivery. This review specially focuses on US Patents of nanoparticles for ocular drug delivery. Nanotechnology is one of the best approaches to overcome challenges of conventional ocular drug delivery. In spite the number of products related to nanotechnology available in market is very less and ophthalmic product related to nanotechnology is still in its earlier stage. FDA website notes that only 21 ocular drugs were approved in the last 10 years; 30 new drugs, if one looks back to 1995. No ocular drugs were approved in 1995 or 2003. It is proved that efficiency of nanoparticles for ocular drug delivery is much better than other novel drug delivery systems in terms of dose, stability, cell targeting, particle size etc. Nanohydrogel, lipid nanoparticles, nanosuspension, etc. are being used successfully in ocular nanotechnology. Even cyclodextrins, soft lenses are also used fruitfully for the same purpose. Some aspects associated with these techniques for ocular delivery are discussed in this review.

Transfersomes are specific deformable vesicles, which are being developed, considering the advantage of phospho-lipids vesicles, for suitable delivery of drug. These are highly elastic in nature, as such they could easily overcome the skin penetration, by squeezing themselves in a self-adapting manner. Also they possess a unique ability to get accommodated with a wide range of solubility and act as an efficient carriers for both low as well as high molecular weight drugs, e.g. analgesic, corticosteroids, hormones, anticancer drugs, insulin, proteins etc with high entrapment efficiency & a unique advantage of protection of the encapsulated drug, from metabolic degradation. However, their major disadvantage arises due to their chemical instability and high susceptibility to oxidative degradation. Transfersomes could be easily prepared using various processes - suspension homogenization process, aqueous lipid suspension process, modified handshaking process and centrifugation process. Transfersomes’ inherent potential advantages are highly utilized in ‘Transdermal Immunization’, ‘Peripheral Drug Targeting’ & for ‘Transdermal Delivery ‘of Insulin, NSAIDs, Heparin, Anti Cancer drugs, etc. Various patent applications have been admitted, using Transfersomes for various applications, e.g., ‘Transcutaneous Administration’ of Antigens, Delivery of larger molecules across nasal mucosa, Intra- Epithelial delivery of chemical agents, Delivery of biologically active drugs, delivery of DNA using lipid vesicles, etc. Recently, marketing approval of Drug ‘diractin’ using ketoprofen has gained its significance for Transferosomal delivery of the drug.

The patents annotated in this section have been selected from various patent databases. The patents annotated in this section are relevant to the articles published in this journal issue, categorized by therapeutic areas/targets and therapeutic agents related to Nanomedicine....