This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin. Both nanoparticles and nanofibers can be used to deliver hydrophobic and hydrophilic drugs and are capable of controlled release for a prolonged period of time. The examples presented provide significant evidence that this area of research has—and will continue to have — a profound impact on both clinical outcomes and the development of new products.
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A wide range of nanoparticles has been explored for the delivery of highly hydrophobic drugs, but very few publications provide comparative data of the performance of different nanoparticles. To address this need, this publication compares poly(lactic-co-glycolic acid) (PLGA) nanoparticles and nanospheres made from tyrosine-derived tri-block copolymers (termed TyroSpheres) for their respective performance as carriers for cyclosporine A (CSA). Using previously reported data on PLGA, we followed similar experimental protocols to evaluate the in vitro characteristics of TyroSpheres. Although there are some similarities between the two particle systems for the delivery of CSA, such as effective encapsulation and epidermal skin penetration, several differences were notable. First, the methods of preparation were different, i.e., self-assembly and emulsion-diffusion-evaporation process for TyroSpheres and PLGA, respectively. Second, TyroSpheres provided 7-day diffusion-controlled release, whereas PLGA nanoparticles provided >21-day erosion-controlled release. Third, the size of TyroSpheres was measured to be ~60–70 nm irrespective of drug loading, whereas the size of PLGA nanoparticles (~100–250 nm) was dependent on drug loading and the method of preparation. Overall, this publication provides a direct comparison between two different types of nanoparticles and illuminates the respective advantages and disadvantages, using CSA as a model for the release of highly hydrophobic drugs.
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The tissue microenvironment has profound effects on tissue-specific regeneration. The 3-dimensional extracellular matrix (ECM) niche influences the linage-specific differentiation of stem cells in tissue. To understand how ECM guides tissue-specific regeneration, we established a series of 3D composite scaffolds containing ECMs derived from different primary cells isolated from a single animal species and assessed their impact on the differentiation of human mesenchymal stem cells (hMSCs). Synthetic microfiber scaffolds (fiber mats) were fabricated by electrospinning tyrosine-derived polycarbonates (pDTEC). The bovine primary fibroblasts, chondrocytes and osteoblasts cultured on the fiber mats produced and assembled their ECMs, infiltrating the pores of the fibrous scaffold. The composite scaffolds were decellularized to remove cellular components, preserve ECM and minimally affect polymer integrity. Characterization of the ECMs derived from different primary cells in the composite scaffolds showed overlapping but distinct compositions. The chondrogenic and osteogenic differentiation of hMSCs on the different composite scaffolds were compared. Our results showed that ECM derived from chondrocytes cultured in synthetic fiber mats promoted the chondrogenic differentiation of hMSC in the presence or absence of soluble inducing factors. ECM derived from co-culture of osteoblasts and chondrocytes promoted osteogenic differentiation in hMSCs better than ECM derived from chondrocytes. This study demonstrated that decellularized ECMs derived from different cell types formed within synthetic fiber scaffolds guide the tissue-specific differentiation of hMSCs. These composite scaffolds may be developed into models to study the mechanisms of ECM-induced tissue regeneration.Graphical Abstract
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