Nanoparticle Tracking Analysis represents a rapid and information-rich multi-parameter nanoparticle characterization technique allowing the user to obtain number frequency particle size distributions of polydisperse nanoparticulate systems. It has resulted in its rapid adoption as an interesting new technique in a wide range of sectors within the pharmaceutical sciences. This Chapter 5 addresses some of the latest work reported in the literature in which NTA has been proposed, used and assessed in the study of nanoparticle-based drug delivery and targeting.
Nanomedicine
It is well established that the use of nanotechnology in medicine and more specifically drug delivery is spreading rapidly. Driven by the diminishing rate of discovery of new biologically active compounds that can be exploited therapeutically to treat disease and with fewer new drugs entering the market every year, interest in the use of nanoparticle’s versatile and multifunctional structures for the delivery of existing drugs has grown rapidly. Nanoparticles offer better pharmacokinetic properties, controlled and sustained release, and targeting of specific cells, tissues or organs such (e.g. in new ways in which to cross the blood-brain barrier). All these features can improve the efficacy of existing drugs (Malam et al., 2011). Nanoparticles in this context have been defined as colloidal systems of submicron size that can be constructed from a large variety of materials in a large variety of compositions. Commonly defined nanoparticle vectors include: liposomes, micelles, dendrimers, solid lipid nanoparticles, metallic nanoparticles, semiconductor nanoparticles and polymeric nanoparticles. Therefore, nanoparticles have been extensively employed to deliver drugs, genes, vaccines and diagnostics into specific cells/tissues (Ram et al., 2011).However, while such nanoparticles are being increasingly used to reduce toxicity and side effects of drugs, it has been recognized that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatin and phospholipids for liposomes to substances of a more chemical nature like various polymers and solid metal containing nanoparticles. It has been previously recognized that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation (De Jong and Borm, 2008, Moquin and Winnik, 2012).
Nanoparticles in Drug Delivery
Given the above, it is not surprising that the characterization of nanoparticles intended for drug delivery has been the subject of a recent review (McNeil, 2011a) in which the benefits of nanotechnology have been described but with warnings concerning the fact that the physical nature of the nanoparticles can interfere with conventional and standardized biocompatibility and immunotoxicity testing protocols. In his further comprehensive review of the subject, McNeil (2011b) has also described many assays to determine physical and chemical properties of nanoparticles including batch-mode dynamic light scattering, MALDI-TOF, zeta potential measurement, AFM, TEM and SEM X-Ray microanalysis of nanoparticles present in tissue or cultured cell thin sections. Nanoparticle Tracking Analysis, being a recently developed technique was not considered in this review but is, however, gaining use in the characterization of nanoparticulate suspensions being developed for drug delivery usage, as is described below. An understanding of the dispersion a distribution of nanoparticle sizes prior to their introduction to cellular systems for cytotoxilogical testing is crucial and NTA has proved useful in this regard compared to other nanoparticle characterization techniques such as DLS (Kendall et al., 2010). Following early work using NTA for the study of sodium caproate mediated promotion of oral drug absorption (Maher et al., 2009), more recent work has used NTA to study holonium (Bult et al., 2010) Moddaresi et al. (2010) used NTA to show that semi-solid gel hyaluronic acid matrices used for topical application of drug delivery nanovesicles (tocopheryl acetate (TA) lipid nanoparticles) did, as expected, inhibit their mobility but deliberate manipulation of the particle mobility in the gel by varying the concentration of HA had little effect on TA delivery showing that drug release from the lipid nanoparticles was the rate limiting step in the delivery process and not the nanoparticle–vehicle–skin interaction. Bhuiyan (2010) showed that localized drug release from thermosensitive liposomes could be induced by hypothermia using NTA to characterize his liposome preparations. More recently, Sunshine et al. (2012), in developing safe and effective delivery system based on poly(beta-amino ester)s (PBAEs) which show great potential as gene delivery reagents because they are easily synthesized and transfect a wide variety of cell types with high efficacy in vitro, have used NTA to determine particle size just prior to subretinal injection. The successful transfection of the RPE in vivo suggested that these nanoparticles could be used to study a number of genetic diseases in the laboratory with the potential to treat debilitating eye diseases. Shirali et al. (2011) used NTA in the development of a poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulation. PLGA nanoparticles are among the most studied polymer nanoformulations for several drugs against different kinds of malignant diseases, thanks to their in vivo stability and tumor localization exploiting the well-documented “enhanced permeation and retention” effect. Similarly, in treating the endemic disease Paracoccidioidomycosis, through a new formulation comprising the sustained release of encapsulated itraconazole in nanostructured PLGA, NTA was used to establish an average size of 174nm and which showed that the encapsulated delivery system exhibited improved performance and reduced cytotoxic effects (Cunha-Azevedo, 2011). PLGA nanoparticles loaded with curcumin have been shown to induce G2/M block in breast cancer cells. Using NTA to show full precipitation of the nanoparticle preparation, the PLGA nanoparticles proved to be completely safe, suggesting a potential utilization of this nanocomplex to improve the intrinsically poor bioavailability of curcumin for the treatment of severe malignant breast cancer (Verderio et al., 2013). Click here to read the full chapterMalvern Instruments provides the materials and biophysical characterization technology and expertise that enable scientists and engineers to understand and control the properties of dispersed systems. These systems range from proteins and polymers in solution, particle and nanoparticle suspensions and emulsions, through to sprays and aerosols, industrial bulk powders and high concentration slurries. Used at all stages of research, development and manufacturing, Malvern’s materials characterization instruments provide critical information that helps accelerate research and product development, enhance and maintain product quality and optimize process efficiency. Our products reflect Malvern’s drive to exploit the latest technological innovations and our commitment to maximizing the potential of established techniques. They are used by both industry and academia, in sectors ranging from pharmaceuticals and biopharmaceuticals to bulk chemicals, cement, plastics and polymers, energy and the environment. Malvern systems are used to measure particle size, particle shape, zeta potential, protein charge, molecular weight, mass, size and conformation, rheological properties and for chemical identification, advancing the understanding of dispersed systems across many different industries and applications. Headquartered in Malvern, UK, Malvern Instruments has subsidiary organizations in all major European markets, North America, Mexico, China, Japan and Korea, a joint venture in India, a global distributor network and applications laboratories around the world. www.malvern.com severine.michel@malvern.com
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