Review on Testosterone Delivery by Natural and Synthetic Nanoparticles

Abstract

IntroductionNatural and synthetic polymers are widely used as drug delivery tools in pharmaceutical and nanomedicine biotechnology [1][2][3][4][5]. Among synthetic polymers, dendrimers, a family of cationic polymers, are promising nonviral vectors for gene and drug delivery because of a well-defined molecular shape, controlled chemical structure, high water solubility, large number of chemically versatile surface groups, and unique architecture [6][7][8]. Natural cationic polymers such as chitosan are attractive candidates for therapeutic applications as they generally are nontoxic, being derived from renewable resources [9]. Biodegradable, biocompatible and nontoxic chitosan nanoparticles are of a major interest in drug delivery systems. They form complexes with antibiotics, anticancer drugs and therapeutic proteins [10][11][12]. Chitosan and its derivatives have the desired properties for safe use as pharmaceutical drug delivery tools. This has prompted accelerated research activities worldwide on chitosan nanoparticles as drug delivery tools [13][14][15][16].Testosterone is the main androgenic hormone which controls many physiological processes such as, sexual functions and secondary sex characteristics, muscle protein metabolism, plasma lipid and bone metabolism [17]. Testosterone can also be used as a natural template to construct semi-synthetic analogues such as dimers, testosterone amide derivatives, as well as testosteronecytotoxic hybrid molecules [18][19][20][21][22]. These novel semi-synthetic molecules can be tested for their biological properties, using diverse spectroscopic methods [18][19][20][21][22][23][24][25]. Synthetic polymers are used as potential nanocarriers to deliver steroids in vitro and in vivo [26][27][28]. Furthermore, chitosan and its derivatives were also tested as delivery tools for transporting steroids [29,30].In this review, the binding efficacies of testosterone with PAMAM dendrimers and chitosan nanoparticles were compared, using multiple spectroscopic, TEM images and molecular modeling results. Structural analysis regarding testosterone binding process and the effect of steroid-polymer conjugation on polymer morphology as well as the possibility of testosterone delivery by PAMAM and chitosan nanoparticles are discussed here. Experimental Transmission electron microscopyThe TEM images were taken using a Philips EM 208S microscope operating at 180 kV. The morphology of the testosterone conjugates with PAMAM dendrimers and chitosan nanoparticles in aqueous solution at pH 7.4 were observed, using transmission electron microscopy. One drop (5-10 µL) of the freshly-prepared mixture [polymer solution (60 µM) + steroid solution (60 µM)] in Tris-HCl buffer (24 ± 1°C) was deposited onto a glow-discharged carbon-coated electron microscopy grid. The excess liquid was absorbed by a piece of filter paper, and a drop of 2% uranyl acetate negative stain was added before drying at room temperature [28]. UV spectroscopyThe UV-Vis spectra were recorded on a Perkin-Elmer Lambda AbstractThe lo...