Abstract

Abstract A variety of organic and inorganic materials have been utilized to generate nanoparticles for drug delivery applications, including polymeric nanoparticles, dendrimers, nanoshells, liposomes, nucleic acid based nanoparticles, magnetic nanoparticles, and virus nanoparticles. The two most commonly used systems are polymeric nanoparticles and liposomes [1, 2]. Controlled release polymer technology has impacted virtually every branch of medicine, including ophthalmology, pulmonary, pain medicine, endocrinology, cardiology, orthopedics, immunology, neurology and dentistry, with several of these systems in clinical practice today such as Atridox, Lupron Depot, Gliadel, Zoladex, Trelstart Depot, Risperidol Consta and Sandostatin LAR. The annual worldwide market of controlled release polymer systems which extends beyond drug delivery is now estimated at $100 billion and these systems are used by over 100 million people each year. Polymeric nanoparticles can deliver drugs in the optimum dosage over time, thus increasing the efficacy of the drug, maximizing patient compliance and enhancing the ability to use highly toxic, poorly soluble, or relatively unstable drugs. These systems can also be used to co-deliver two or more drugs for combination therapy [3]. The surface engineering of these nanoparticles may yield them “stealth” to prolong their residence in blood [4] and the functionalization of these particles with targeting ligands can differentially target their delivery or uptake by a subset of cells [5], further increasing their specificity and efficacy [6]. The successful clinical translation of therapeutic nanoparticles requires optimization of many distinct parameters including: variation in the composition of the carrier system, drug loading efficiency, surface hydrophilicity, surface charge, particle size, density of possible ligands for targeting, etc., resulting in a large number of potential variables for optimization which is impractical to achieve using a low throughput approach. More recently combinatorial approaches have been developed to precisely engineer nanoparticles and screen multiple nanoparticle characteristics simultaneously with the goal of identifying formulations with the desired physical and biochemical properties for each specific application [7]. The goal of this talk is to review our efforts in the design and optimization of polymeric nanoparticles for medical applications, which formed the foundation for the clinical translation of the first-in-human targeted and controlled-release nanoparticles, BIND-014 and SEL-068 [8, 9].

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