Photothermal Activatable Mucoadhesive Fiber Mats for On-Demand Delivery of Insulin via Buccal and Corneal Mucosa

Electrospun fiber mats loaded with therapeutics have gained considerable attention as a versatile tool in the biomedical field. While these bandages are largely based on fast-dissolving polymers to release the cargo, stimuli-responsive fiber mats have the advantages of providing a timely and spatially controlled drug delivery platform, which can be refilled and reused several times. These benefits make electrospun fiber patches original platforms for painless and convenient on-demand hormone release. Because of the high need of more convenient and non-invasive methods for delivering insulin, a hormone that is currently used to treat hundred million people with diabetes worldwide, we have investigated the tremendous potential of reduced graphene oxide modified poly(acrylic acid) based fiber mats as an original platform for buccal and corneal insulin delivery on-demand. The PAA@rGO hydrogel-like fibers rendered water-insoluble by incorporating β-cyclodextrin, followed by thermal cross-linking, which showed adequate tensile strength along with high adsorption capacity of insulin at pH 7 and good recyclability. The fiber mats maintained good fibrous morphology and high loading efficiency even after five loading-release cycles. The mucoadhesive nature of the fibers allowed their application for insulin delivery via the eye cornea and the buccal mouth lining, as evidenced in ex vivo studies. Insulin loaded PAA@rGO hydrogel-like fibers showed an insulin flux via buccal lining of pigs of 16.6 ± 2.9 μg cm-2 h-1 and 24.3 ± 3.1 μg cm-2 h-1 for porcine cornea. Testing on healthy adult volunteers confirmed the excellent, mucoadhesive nature of the bandage, with three out of six volunteers feeling completely comfortable (note 8.3) while wearing the patches in the buccal cavity.The Centre National de la Recherche Scientifique (CNRS), the University of Lille, the Hauts-de-France region, and the CPER “Photonics for Society” are acknowledged for financial support. This work was partly supported by the French Renatech network. A.V. thanks the i-SITE foundation of the University of Lille for a PhD fellowship. This project has received funding from the European Union’s Horizon 2020 Research and Innovation Staff Exchange (RISE) Marie Skłodowska-Curie Actions under grant agreement No 690836.Peer reviewe

Drug Delivery Systems from Self-Assembly of Dendron-Polymer Conjugates †

This review highlights the utilization of dendron-polymer conjugates as building blocks for the fabrication of nanosized drug delivery vehicles. The examples given provide an overview of the evolution of these delivery platforms, from simple micellar containers to smart stimuli- responsive drug delivery systems through their design at the macromolecular level. Variations in chemical composition and connectivity of the dendritic and polymeric segments provide a variety of self-assembled micellar nanostructures that embody desirable attributes of viable drug delivery systems

Dynamics of doctor–patient relationship: A cross-sectional study on concordance, trust, and patient enablement

Background:The rapid pace of medical advances coupled with specialization and super-specialization, is eroding the traditional doctor-patient relationship. Objective:(a) To study the determinants of core dimensions, such as, concordance, trust, and enablement in a doctor-patient relationship; (b) to explore associations, if any, among these core dimensions. Materials and Methods: A cross-sectional study design with both quantitative and qualitative methods was employed. One hundred and ninety-eight outdoor patients were interviewed as part of the quantitative study. Three dimensions of the doctor-patient relationship, that is, physician patient concordance, trust in physician, and patient enablement were assessed using validated tools. Focus group interviews using an open-ended format among few physicians was carried out as part of the qualitative study. Results: In the quantitative analysis most of the sociocultural factors did not show any significant association with the doctor-patient relationship. However, gender was significantly and strongly associated with trust in the physician. Female patients showed a much lower trust in the physician (50%) as compared to male patients (75%) (OR = 0.33, 95% CI 0.17 - 0.64, Chi Sq = 12.86, P = 0.0003). A qualitative study revealed language and culture, alternative medicines, commercialization of medicine, and crowding at specialist and super-specialist clinics as barriers to a good doctor-patient relationship. Better concordance was associated with improved trust in the doctor (OR = 5.30, 95% CI 2.06 - 13.98, Chi Sq = 14.46, P = 0.0001), which in turn was associated with improved patient enablement (OR = 3.89, 95% CI = 1.60 - 9.64, Chi Sq = 10.15, P = 0.001). Conclusion:Good doctor-patient concordance (agreement) leads to better trust in the physician, which in turn leads to better patient enablement, irrespective of the sociocultural determinants

Dendrimers and Dendrons as Versatile Building Blocks for the Fabrication of Functional Hydrogels

Hydrogels have emerged as a versatile class of polymeric materials with a wide range of applications in biomedical sciences. The judicious choice of hydrogel precursors allows one to introduce the necessary attributes to these materials that dictate their performance towards intended applications. Traditionally, hydrogels were fabricated using either polymerization of monomers or through crosslinking of polymers. In recent years, dendrimers and dendrons have been employed as well-defined building blocks in these materials. The multivalent and multifunctional nature of dendritic constructs offers advantages in either formulation or the physical and chemical properties of the obtained hydrogels. This review highlights various approaches utilized for the fabrication of hydrogels using well-defined dendrimers, dendrons and their polymeric conjugates. Examples from recent literature are chosen to illustrate the wide variety of hydrogels that have been designed using dendrimer- and dendron-based building blocks for applications, such as sensing, drug delivery and tissue engineering

Molecularly Imprinted Polymer-Coated Inorganic Nanoparticles: Fabrication and Biomedical Applications

Molecularly imprinted polymers (MIPs) continue to gain increasing attention as functional materials due to their unique characteristics such as higher stability, simple preparation, robustness, better binding capacity, and low cost. In particular, MIP-coated inorganic nanoparticles have emerged as a promising platform for various biomedical applications ranging from drug delivery to bioimaging. The integration of MIPs with inorganic nanomaterials such as silica (SiO2), iron oxide (Fe3O4), gold (Au), silver (Ag), and quantum dots (QDs) combines several attributes from both components to yield highly multifunctional materials. These materials with a multicomponent hierarchical structure composed of an inorganic core and an imprinted polymer shell exhibit enhanced properties and new functionalities. This review aims to provide a general overview of key recent advances in the fabrication of MIPs-coated inorganic nanoparticles and highlight their biomedical applications, including drug delivery, biosensor, bioimaging, and bioseparation

Trastuzumab targeted micellar delivery of docetaxel using dendron-polymer conjugates

Incorporation of a therapeutic antibody into nanosized drug delivery systems can improve their target specificity. This work reports an antibody-conjugated targeted delivery system composed of polymer-dendron conjugates. Trastuzumab is chosen as the targeting moiety, since it is clinically used against tumor cells expressing HER2 receptors. A micellar delivery system was generated using amphiphilic polymer-dendron conjugates containing a fourth-generation polyester dendron as the hydrophobic block and a linear poly(ethylene glycol) (PEG) chain as the hydrophilic block. After preparation of docetaxel loaded (ca. 10% wt) micelles, trastuzumab was conjugated onto the micellar shell using an amidation reaction. Micelles remained stable after conjugation of the antibody, with a slight increase in size from 179 nm to 185 nm upon functionalization. Docetaxel release was determined to be responsive to acidic pH, and over the course of 30 h, 54% drug release was measured in acidic media, whereas it was around 30% under neutral conditions. Cytotoxicity experiments on MCF-7 and SK-OV-3 cell lines displayed improved toxicity levels for targeted micelles in comparison with the non-targeted counterparts, whereas pulse-chase experiments indicated effectiveness of micellar formulations and the presence of targeting groups. Cellular internalization experiments using fluorescence microscopy and flow cytometry further demonstrated the enhanced cellular uptake of antibody conjugated targeted micelles

Hydrophilic cross-linked polymeric nanofibers using electrospinning : imparting aqueous stability to enable biomedical applications

Polymeric nanofibers are finding a growing number of applications in various areas of biomedical sciences such as diagnostics, therapeutic delivery, and tissue engineering. Since such applications entail interfacing these materials with the biological milieu, it is often necessary that these nanofibers are hydrophilic in nature, yet stable in an aqueous environment. To date, several approaches to impart stabilization to polymeric nanofibers obtained using electrospinning have been developed. Various strategies utilizing chemical cross-linking of polymers have been exploited to impart stabilization of functional nanofibers fabricated using polymers that are soluble in the aqueous environment. This review highlights the various approaches developed to date for providing stabilization to hydrophilic polymeric nanofibers, along with showcasing the utilization of hydrophilic polymeric nanofibers in several biomedical applications