Abstract. Nanomedicine refers to biomedical and pharmaceutical applications of nanosized cargos of drugs/vaccine/DNA therapeutics including nanoparticles, nanoclusters, and nanospheres. Such particles have unique characteristics related to their size, surface, drug loading, and targeting potential. They are widely used to combat disease by controlled delivery of bioactive(s) or for diagnosis of life-threatening problems in their very early stage. The bioactive agent can be combined with a diagnostic agent in a nanodevice for theragnostic applications. However, the formulation scientist faces numerous challenges related to their development, scale-up feasibilities, regulatory aspects, and commercialization. This article reviews recent progress in the method of development of nanoparticles with a focus on polymeric and lipid nanoparticles, their scale-up techniques, and challenges in their commercialization.
The unique properties of poly(amido)amine dendrimers such as nano size, multifunctional surface, ability to encapsulate and bind the guest molecules, efficient membrane transport and shelf-life stability have made them a promising carrier in drug delivery. The two key applications of dendrimers include increasing the solubility and sustained release of molecules, and drug targeting by grafting the cell-specific ligands on the surface. Despite their potential in drug delivery, inherent cytotoxicity, reticuloendothelial system uptake and hemolysis limit their use in clinical applications. Research groups have been working on surface modification methods to mitigate these problems. Herein we present a brief discussion on current surface modification approaches to: i) increase targeting efficiency; ii) increase the cellular permeability for enhanced absorption; iii) increase gene transfection efficiency; and iv) decrease the toxicity of the dendrimers, with a few classic examples. As the knowledge of relationship between the dendrimer surface chemistry and its mode of interactions with cell membrane is developed, so do the modifications of dendrimer structure to render them nontoxic, biocompatible, biodegradable and improve their pharmacodynamic and pharmacokinetic properties. Development of multifunctional dendrimers with each functional unit imparting a distinct characteristic feature such as target cell recognition, enhanced cellular transport, reduction in reticuloendothelial system uptake and stability in in vivo environment holds a great potential for future biomedical applications.
The challenges in SN38 drug delivery may be overcome by two ways: ensuring multiple layers of protection against degradation and slow but sustained release of therapeutically effective drug concentrations. It may also be achieved by preparing a polymer-drug conjugate and further encapsulating the conjugate in suitable carrier system; tumor-targeted SN38 delivery by using immunoconjugates, enzyme-activated prodrug therapy and antibody-directed nanoparticle delivery. However, selection of a suitable ligand for tumor targeting and use of safe and biocompatible nanoparticle systems play an important role in realizing this goal.
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