João Pedro Poças Martins

A comprehensive review of the neonatal Fc receptor and its application in drug delivery

Advances in the understanding of neonatal Fc receptor (FcRn) biology and function have demonstrated that this receptor, primarily identified for the transfer of passive immunity from mother infant, is involved in several biological and immunological processes. In fact, FcRn is responsible for the long half-life of IgG and albumin in the serum, by creating an intracellular protein reservoir, which is protected from lysosomal degradation and, importantly, trafficked across the cell. Such discovery has led researchers to hypothesize the role for this unique receptor in the controlled delivery of therapeutic agents. A great amount of FcRn-based strategies are already under extensive investigation, in which FcRn reveals to have profound impact on the biodistribution and half-life extension of therapeutic agents. This review summarizes the main findings on FcRn biology, function and distribution throughout different tissues, together with the main advances on the FcRn-based therapeutic opportunities and model systems, which indicate that this receptor is a potential target for therapeutic regimen modification.

Will dapivirine redeem the promises of anti-HIV microbicides? Overview of product design and clinical testing.

Microbicides are being developed in order to prevent sexual transmission of HIV. Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is one of the leading drug candidates in the field, currently being tested in various dosage forms, namely vaginal rings, gels, and films. In particular, a ring allowing sustained drug release for 1month is in an advanced stage of clinical testing. Two parallel phase III clinical trials are underway in sub-Saharan Africa and results are expected to be released in early 2016. This article overviews the development of dapivirine and its multiple products as potential microbicides, with particular emphasis being placed on clinical evaluation. Also, critical aspects regarding regulatory approval, manufacturing, distribution, and access are discussed.

Multifunctional Nanotube–Mucoadhesive Poly(methyl vinyl ether‐co‐maleic acid)@Hydroxypropyl Methylcellulose Acetate Succinate Composite for Site‐Specific Oral Drug Delivery

An advanced oral drug delivery system that can effectively deliver drugs with poor oral bioavailability is strongly desirable. Herein, a multifunctional nano-in-micro structured composite is developed by encapsulation of the mucoadhesive poly(methyl vinyl ether-co-maleic acid) modified halloysite nanotubes (HNTs) with the pH-responsive hydroxypropyl methylcellulose acetate succinate by the microfluidics to control the drug release, increase cell-particle interaction, and improve drug absorption. The microparticles show spherical shape, homogeneous particle size distribution (58 ± 1 µm), and pH-responsive dissolution behavior at pH > 6, and they prevent the premature release of curcumin in simulated pH conditions of the stomach and immediately release the curcumin in simulated pH conditions of the small intestine. The surface modification of HNT with mucoadhesive poly(methyl vinyl ether-co-maleic acid) significantly enhances its interactions with the intestinal Caco-2/HT29-MTX cells and the mouse small intestines, and increases the permeability of curcumin across the co-cultured Caco-2/HT29-MTX cell monolayers by about 13 times compared to the free curcumin. Therefore, the developed multifunctional nanotube-mucoadhesive poly(methyl vinyl ether-co-maleic acid)@hydroxypropyl methylcellulose acetate succinate composite is a promising oral drug delivery system for drugs with poor oral bioavailability.

Development of virtual reality game-based interfaces for civil engineering education

Virtual Reality (VR) is gradually becoming a part of the life of the average person as hard-ware prices become more affordable for the end user. A growing variety of hardware allows users to engage in a series of immersive experiences for ludic, educational or even professional activities. In this regard, the diversity of affordable solutions could provide an alternative to highly immersive, but expensive environments such as, CAVE experiences [1]. The development of VR technologies is starting to spread its influence to the AECO (Architecture, Engineering, Construction and Operations) sector through the creation of new work methodologies and techniques, as well as original interfaces for communication. Creating new tools for the discussion of topics and providing collaborative work among participants with different backgrounds provides opportunities not only for the industry, but also for applications in education. The development of VR applications and its outcomes, regarding the acceptance (or lack of it) from the students will be the focus of this paper. The description of three case studies will be fully detailed, providing data analysis from each one of the tests conducted.

Communication from the periphery to the hypothalamus through the blood–brain barrier: An in vitro platform

One of the major routes of communication from the peripheral systems to the hypothalamus, the core structure of body homeostasis, is the humoral transmission through the blood-brain barrier (BBB). The BBB cultures are the in vitro model of choice to depict the mechanisms behind blood-brain interplay. Still, this strategy excludes the integration of the brain tissue response and, therefore, the resulting output might be limited. In this study, two in vitro assays were established: BBB coculture model and hypothalamic organotypic cultures. The combination of these two assays was used as a platform to address the two critical steps in the humoral transmission through the BBB to the brain: blood-BBB/BBB-brain. The in vitro model of the BBB was performed according to a coculture system using a brain microvascular endothelial cell line (bEnd.3) and primary astrocytes. The expression of junctional molecules as claudin-5, ZO-1, occludin and VE-cadherin was observed in the bEnd.3 cell-cell contact, confirming the BBB phenotype of these endothelial cells. Moreover, the transendothelial electrical resistance (TEER) values (71.1±9.4Ω× cm(2)) and the permeability coefficients (Pe) obtained in the transendothelial flux test (3.3±0.11×10(-6)cm/sec) support high integrity of the established barrier. The hypothalamic organotypic cultures were prepared from 8-days-old C57Bl/6 mice brains, based on the air-medium interface culture method. High cell viability (82±9.6%) and a dense neuronal network were achieved. The stimulation with dexamethasone resulted in an increased neuropeptide (NPY) expression, confirming the responsiveness of the neuronal system of these organotypic cultures. After optimization and characterization of each assay, the functionality of the platform was validated through the evaluation of the hypothalamic response to deep wound encompassing skin and muscle in mice. Results allowed to identify increased NPY activity in hypothalamic slices in response to peripheral signals within the plasma from wounded animals when compared with non-injured animals after surpassing and/or interacting with the BBB. This differential NPY response between the different animal conditions validated the functionality of the in vitro platform. In conclusion, this approach can be greatly anticipated as a useful tool for studying biologic or pharmacological circulating molecules and their impact on the hypothalamic activity.

The importance of microfluidics for the preparation of nanoparticles as advanced drug delivery systems

ABSTRACT Introduction: Nanoparticles are anticipated to overcome persistent challenges in efficient drug delivery, but the limitations associated with conventional methods of preparation are resulting in slow translation from research to clinical applications. Due to their enormous potential, microfluidic technologies have emerged as an advanced approach for the development of drug delivery systems with well-defined physicochemical characteristics and in a reproducible manner. Areas covered: This review provides an overview of microfluidic devices and materials used for their manufacturing, together with the flow patterns and regimes commonly used for nanoparticle preparation. Additionally, the different geometries used in droplet microfluidics are reviewed, with particular attention to the co-flow geometry used for the production of nanoparticles. Finally, this review summarizes the main and most recent nanoparticulate systems prepared using microfluidics, including drug nanosuspensions, polymeric, lipid, structured, and theranostic nanoparticles. Expert opinion: The production of nanoparticles at industrial scale is still a challenge, but the microfluidic technologies bring exciting opportunities to develop drug delivery systems that can be engineered in an easy, cost-effective and reproducible manner. As a highly interdisciplinary research field, more efforts and general acceptance are needed to allow for the translation of nanoparticulate drug delivery systems from academic research to the clinical practice.

Virtual and augmented reality game-based applications to civil engineering education

Gaming scenarios and virtual environments have shown beneficial results in Engineering Education. Various activities conducted in different fields demonstrate that students reveal appraisal for the integration of innovative technologies such as Virtual or Augmented Reality in the learning process. In this paper, Virtual Reality (VR) applications developed by first year students during an introductory class of the Integrated Masters in Civil Engineering are described. Additionally, two trials concerning the application of VR and Augmented Reality (AR) to Civil Engineering held at a local school (K-12 students) are also detailed. After the tests, students were surveyed and data was collected. Results and considerations are revealed in the final sections of this paper.

Engineered Multifunctional Albumin-Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin

The last decade has seen remarkable advances in the development of drug delivery systems as alternative to parenteral injection-based delivery of insulin. Neonatal Fc receptor (FcRn)-mediated transcytosis has been recently proposed as a strategy to increase the transport of drugs across the intestinal epithelium. FcRn-targeted nanoparticles (NPs) could hijack the FcRn transcytotic pathway and cross the epithelial cell layer. In this study, a novel nanoparticulate system for insulin delivery based on porous silicon NPs is proposed. After surface conjugation with albumin and loading with insulin, the NPs are encapsulated into a pH-responsive polymeric particle by nanoprecipitation. The developed NP formulation shows controlled size and homogeneous size distribution. Transmission electron microscopy (TEM) images show successful encapsulation of the NPs into pH-sensitive polymeric particles. No insulin release is detected at acidic conditions, but a controlled release profile is observed at intestinal pH. Toxicity studies show high compatibility of the NPs with intestinal cells. In vitro insulin permeation across the intestinal epithelium shows approximately fivefold increase when insulin is loaded into FcRn-targeted NPs. Overall, these FcRn-targeted NPs offer a toolbox in the development of targeted therapies for oral delivery of insulin.

3D printing: prospects and challenges

Regenerative medicine is an emergent multidisciplinary field that aims to significantly improve tissue repair or restoration, thus focusing on tissue engineering (TE) in regenerative medicine is inevitable. TE has created a useful ground in which biomaterials science witnessed a huge jump in improving diagnosis and treatment during recent years. TE brings together relevant knowledge from physical sciences, molecular engineering, biotechnology, and medicine toward ameliorated regrowing of the damaged tissue when the body is not able to completely heal itself. three-dimensional (3D) printing comes as a branch of TE technologies, allowing the synthesis of 3D constructs that provide key physiological environments for cell growing. In addition, nanoengineered systems hold tremendous potential in regenerative medicine, as their properties can be fine-tuned to promote tighter communication between cells and implantable materials. In Subchapter 4.1, intelligent biomaterials, 3D printing–based technologies, and nanosystems for imaging and drug delivery are presented and discussed, with special emphasis to their current applications toward a sounding impact in regenerative medicine. While the use and applicability of nanotechnology is swiftly expanding in several areas of biomedical engineering, its utility has not been fully realized in 3D bioprinting. Nanostructured materials seem to have enormous potential in bioprinting, as even a small fraction of nanoparticle loading can remarkably enrich the printability of bioinks without affecting the viability of the encapsulated cells, and in many cases enhancing overall cell behavior, such as differentiation, proliferation, electrical conductivity, and so on. Additionally, nanomaterials enable easy surface modification with specific biochemical factors or cellular ligands to improve cell adhesion, signaling, and specific cell functions. Subchapter 4.2 provides a general introduction to the background and motivation of using nanomaterials in tissue engineering and regenerative medicine by means of 3D bioprinting. We provide an overview of the current literature on some of the frequently employed nanomaterials in developing hybrid bioinks for 3D bioprinting applications, and describe a range of bioink properties that can be enhanced by the inclusion of specific nanoparticles. In addition, we discuss potential toxicity issues that may arise from the use of nanofilled bioinks, while advocating thorough screening of nanomaterials to avoid undesirable or toxic side effects.

Chapter 4 – 3D printing: prospects and challenges

Regenerative medicine is an emergent multidisciplinary field that aims to significantly improve tissue repair or restoration, thus focusing on tissue engineering (TE) in regenerative medicine is inevitable. TE has created a useful ground in which biomaterials science witnessed a huge jump in improving diagnosis and treatment during recent years. TE brings together relevant knowledge from physical sciences, molecular engineering, biotechnology, and medicine toward ameliorated regrowing of the damaged tissue when the body is not able to completely heal itself. three-dimensional (3D) printing comes as a branch of TE technologies, allowing the synthesis of 3D constructs that provide key physiological environments for cell growing. In addition, nanoengineered systems hold tremendous potential in regenerative medicine, as their properties can be fine-tuned to promote tighter communication between cells and implantable materials. In Subchapter 4.1, intelligent biomaterials, 3D printing–based technologies, and nanosystems for imaging and drug delivery are presented and discussed, with special emphasis to their current applications toward a sounding impact in regenerative medicine. While the use and applicability of nanotechnology is swiftly expanding in several areas of biomedical engineering, its utility has not been fully realized in 3D bioprinting. Nanostructured materials seem to have enormous potential in bioprinting, as even a small fraction of nanoparticle loading can remarkably enrich the printability of bioinks without affecting the viability of the encapsulated cells, and in many cases enhancing overall cell behavior, such as differentiation, proliferation, electrical conductivity, and so on. Additionally, nanomaterials enable easy surface modification with specific biochemical factors or cellular ligands to improve cell adhesion, signaling, and specific cell functions. Subchapter 4.2 provides a general introduction to the background and motivation of using nanomaterials in tissue engineering and regenerative medicine by means of 3D bioprinting. We provide an overview of the current literature on some of the frequently employed nanomaterials in developing hybrid bioinks for 3D bioprinting applications, and describe a range of bioink properties that can be enhanced by the inclusion of specific nanoparticles. In addition, we discuss potential toxicity issues that may arise from the use of nanofilled bioinks, while advocating thorough screening of nanomaterials to avoid undesirable or toxic side effects.