Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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Principles of nanoparticle design for overcoming biological barriers to drug delivery

The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

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Cancer nanomedicine: progress, challenges and opportunities.

Polydopamine and Its Derivative Materials: Synthesis and Promising Applications in Energy, Environmental, and Biomedical Fields

In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release.

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Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

https://cyberleninka.org/article/n/933162.pdf

Hydrogels in drug delivery: progress and challenges

Supramolecular nanofibers self-assembled from cationic small molecules derived from repurposed poly(ethylene teraphthalate) for antibiotic delivery.

Poly(D,L-lactide-co-glycolide) (PLG, 65:35) was used to encapsulate bovine serum albumin (BSA) using a water-in-oil-in-water (W/O/W) double emulsion solvent extraction technique. To investigate the effects of an inner water/oil ratio on microsphere characteristics, microspheres were fabricated using four different formulations with a fixed oil volume of 12 ml and the inner aqueous phase volume of 0.2 ml, 0.3 ml, 0.4 ml or 0.5 ml, respectively. Spherical microspheres were obtained after collection by filtration for formulations employing any of the four different inner water/oil ratios. However, microspheres with smaller inner water volumes tend to collapse after vacuum drying. The surface of the formulation with a higher inner water/oil ratio was shown to possess many more pores than that of the formulations with lower inner water/ oil ratios. These pores may facilitate the water withdrawal during vacuum drying. Furthermore, microspheres with the lowest inner water/oil ratio (1/60) had higher initial burs...

Effects of inner water volume on the peculiar surface morphology of microspheres fabricated by double emulsion technique

The Landau–Lifshitz–Gilbert (LL-G) formula has been widely used in modeling of complex permeability of magnetic thin films and particle composites. In this paper, a approach which is based on Landau–Lifshitz ferromagnetic resonance (LL-FMR) model has been developed to calculate the complex permeability of magnetic particles/insulator matrix composite. It has found that the LL-FMR model can be used to compute the intrinsic permeability of a magnetic particle with different alignments of its magnetic domains with the respect to the incident wave. Through integration with respect to its resonant frequency, this method offers a neat closed-form formula for the case of isotropic composite. Its results compared relatively well with our previous method which computes the isotropic permeability by taking the average of the permeability of a large number of randomly oriented magnetic domains with respect to incident wave based on the LL-G model. For carbonyl bcc-Fe and Fe3O4, the calculated permeability agrees rel...

Calculation of complex permeability of magnetic composite materials using ferromagnetic resonance model

https://www.rsc.org/suppdata/py/c1/c1py00272d/c1py00272d.pdf

Facile routes to star polymersvia an organocatalytic approach

Gene transfer to the corneal endothelium has potential in preventing corneal transplant rejection. In this study, we transfected mouse corneal endothelial cells (MCEC) with a class of novel arginine-rich oligopeptides. The peptides featured a tri-block design and mediated reporter gene expression in MCEC more efficiently than the commercial polyethylenimine standard. The functionality of each block was demonstrated to critically influence the performance of the peptide. Results from confocal imaging and flow cytometry then showed that energy-dependent endocytosis was the dominant form of uptake and multiple pathways were involved. Additionally, uptake was strongly dependent on interactions with cell-surface heparan sulphate. Fluorescence resonance energy transfer studies revealed that the peptide/DNA entered cells as an associated complex and some will have dissociated by 8.5 h. Large-scale accumulation of uncondensed DNA within the nucleus can also be observed by 26 h. Finally, as a proof of biological relevance, we transfected MCEC with plasmids encoding for the functional indoleamine 2,3-dioxygenase (IDO) enzyme. We then demonstrated that the expressed IDO could catalyse the degradation of l-tryptophan, which in turn suppressed the growth of CD4+ T-cells in a proliferation assay.

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Yi Yan Yang

Papers

Supramolecular nanofibers self-assembled from cationic small molecules derived from repurposed poly(ethylene teraphthalate) for antibiotic delivery.

Effects of inner water volume on the peculiar surface morphology of microspheres fabricated by double emulsion technique

Calculation of complex permeability of magnetic composite materials using ferromagnetic resonance model

Facile routes to star polymersvia an organocatalytic approach

Oligopeptide-mediated gene transfer into mouse corneal endothelial cells: expression, design optimization, uptake mechanism and nuclear localization