Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases; for example, by allowing the targeted delivery of a drug to particular subsets of cells. However, so far, such nanoparticles have not proved capable of surmounting all of the biological barriers required to achieve this goal. Nevertheless, advances in nanoparticle engineering, as well as advances in understanding the importance of nanoparticle characteristics such as size, shape and surface properties for biological interactions, are creating new opportunities for the development of nanoparticles for therapeutic applications. This Review focuses on recent progress important for the rational design of such nanoparticles and discusses the challenges to realizing the potential of nanoparticles.

Strategies in the design of nanoparticles for therapeutic applications

Chitosan-based hydrogels for controlled, localized drug delivery

Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers.

Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery.

Polymers for Drug Delivery Systems

Chemistries that Facilitate Nanotechnology Kim E. Sapsford,† W. Russ Algar, Lorenzo Berti, Kelly Boeneman Gemmill,‡ Brendan J. Casey,† Eunkeu Oh, Michael H. Stewart, and Igor L. Medintz*,‡ †Division of Biology, Department of Chemistry and Materials Science, Office of Science and Engineering Laboratories, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States ‡Center for Bio/Molecular Science and Engineering Code 6900 and Division of Optical Sciences Code 5611, U.S. Naval Research Laboratory, Washington, D.C. 20375, United States College of Science, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, California 95817, United States Sotera Defense Solutions, Crofton, Maryland 21114, United States

Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology.

A review of stimuli-responsive nanocarriers for drug and gene delivery

The brain is a delicate organ, and evolution built very efficient ways to protect it. Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Many existing pharmaceuticals are rendered ineffective in the treatment of cerebral diseases due to our inability to effectively deliver and sustain them within the brain. General methods that can enhance drug delivery to the brain are, therefore, of great interest. Despite aggressive research, patients suffering from fatal and/or debilitating central nervous system (CNS) diseases, such as brain tumors, HIV encephalopathy, epilepsy, cerebrovascular diseases and neurodegenerative disorders, far outnumber those dying of all types of systemic cancer or heart disease. The clinical failure of much potentially effective therapeutics is often not due to a lack of drug potency but rather to shortcomings in the method by which the drug is delivered. Treating CNS diseases is particularly challenging because a variety of formidable obstacles often impede drug delivery to the brain and spinal cord. By localizing drugs at their desired site of action one can reduce toxicity and increase treatment efficiency. In response to the insufficiency in conventional delivery mechanisms, aggressive research efforts have recently focused on the development of new strategies to more effectively deliver drug molecules to the CNS. This review intends to detail the recent advances in the field of brain-targeting, rational drug design approach and drug delivery to CNS. To illustrate the complexity of the problems that have to be overcome for successful brain targeting, a brief intercellular characterization of the blood-brain barrier (BBB) is also included.

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Drug delivery to the central nervous system: a review.

Improved oral bioavailability and brain transport of Saquinavir upon administration in novel nanoemulsion formulations.

Many drugs are not being effectively and efficiently delivered using conventional drug delivery approach to brain or central nervous system (CNS) due to its complexity. The brain and the central nervous system both have limited accessibility to blood compartment due to a number of barriers. Many advanced and effective approaches to brain delivery of drugs have emerged in recent years. Intranasal drug delivery is one of the focused delivery options for brain targeting, as the brain and nose compartments are connected to each other via the olfactory 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. 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. This review will discuss some pertinent issues to be considered and challenges to brain targeted intranasal drug delivery. A few marketed and investigational drug formulations will also be discussed.

Intranasal drug delivery for brain targeting.

Purpose: A niosome based transdermal drug delivery system of Nimesulide (NIM) was developed and extensively characterized and evaluated for in-vitro per- formance followed by in-vivo evaluation in rats by carrag- eenan induced rat paw edema method. Method: Niosomes were prepared by lipid film hydration technique using tweens and spans. Preparation of niosomes was opti- mized for highest percent drug entrapment (PDE). The prepared niosomes were incorporated into 1% carbopol gel base and the system was evaluated for drug diffusion across human cadaver skin (HCS) using modified validated diffusion cell. The drug retention studies in niosomes were performed at refrigerated temperature (2° C - 8° C) and at room temperature (25° C±2° C) for the period of 2 months. In-vivo performance of plain drug gel, niosomally- entrapped drug in carbopol gel base and marketed formu- lation were evaluated using acute rat paw edema method. Results: Highest mean percentage edema inhibition (PEI) was observed for niosomal nimesulide gel after 24 hours i.e. 66.68%±5.19% compared to plain drug gel i.e. 12.57%±1.78% and marketed NIM formulation i.e. 20.49%±0.91%. Conclusion: Findings of this investiga- tion conclusively demonstrate prolongation of drug release and increase in amount of drug retention into the skin and permeation across the skin after niosomal encapsulation of NIM. Developed nimesulide niosomal gel formulation has also demonstrated enhanced anti-inflammatory activity compared to plain drug gel and marketed formulation.

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Aliasgar Shahiwala

Papers

A review of stimuli-responsive nanocarriers for drug and gene delivery

Drug delivery to the central nervous system: a review.

Improved oral bioavailability and brain transport of Saquinavir upon administration in novel nanoemulsion formulations.

Intranasal drug delivery for brain targeting.

Studies in topical application of niosomally entrapped Nimesulide.