Recent advances in micro-electro-mechanical devices for controlled drug release applications

In recent years, controlled release of drugs has posed numerous challenges with the aim of optimizing parameters such as the release of the suitable quantity of drugs in the right site at the right time with the least invasiveness and the greatest possible automation. Some of the factors that challenge conventional drug release include long-term treatments, narrow therapeutic windows, complex dosing schedules, combined therapies, individual dosing regimens, and labile active substance administration. In this sense, the emergence of micro-devices that combine mechanical and electrical components, so called micro-electro-mechanical systems (MEMS) can offer solutions to these drawbacks. These devices can be fabricated using biocompatible materials, with great uniformity and reproducibility, similar to integrated circuits. They can be aseptically manufactured and hermetically sealed, while having mobile components that enable physical or analytical functions together with electrical components. In this review we present recent advances in the generation of MEMS drug delivery devices, in which various micro and nanometric structures such as contacts, connections, channels, reservoirs, pumps, valves, needles, and/or membranes can be included in their design and manufacture. Implantable single and multiple reservoir-based and transdermal-based MEMS devices are discussed in terms of fundamental mechanisms, fabrication, performance, and drug release applications.Fil: Villarruel Mendoza, Luis A.. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; ArgentinaFil: Scilletta, Natalia Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; ArgentinaFil: Bellino, Martin Gonzalo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; ArgentinaFil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Catalano, Paolo Nicolás. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Microfluidic Platforms for Evaluation of Nanobiomaterials: a Review

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Microfluidic Platforms for Evaluation of Nanobiomaterials: A Review

Biomaterials, especially those based on nanomaterials, have emerged as critical tools in biomedical applications. The applications encompass a wide range such as implantable devices, tissue regeneration, drug delivery, diagnostic systems, and molecular printing. The type of materials used also covers a wide range: metals (permanent and degradable), polymers (permanent and degradable), carbon nanotubes, and lipid nanoparticles. This paper explores the use of microfluidic platforms as a high-throughput research tool for the evaluation of nanobiomaterials. Typical screening of such materials involves cell/tissue cultures to determine attributes such as cell adhesion, proliferation, differentiation, as well as biocompatibility. In addition to this, other areas such as drug delivery and toxicity can also be evaluated via microfluidics. Traditional approach for screening of such materials is very time-consuming, and a lot of animals should be sacrificed since it involves one material and a single composition or concentration for a single test. The microfluidics approach has the advantage of using multiple types of drugs and their concentration gradients to simultaneously study the effect on the nanobiomaterial and its interaction with cell/tissue. In addition to this, microfluidics provides a unique environment to study the effect of cell-to-extracellular interaction and cell-to-cell communication in the presence of the nanobiomaterials

3D printed implantable drug delivery devices for women’s health: Formulation challenges and regulatory perspective

Modern pharmaceutical interventions are shifting from traditional “one-size-fits-all” approaches toward tailored therapies. Following the regulatory approval of Spritam®, the first marketed drug manufactured using three-dimensional printing (3DP) technologies, there is a precedence set for the use of 3DP in the manufacture of pharmaceutical products. The involvement of 3DP technologies in pharmaceutical research has demonstrated its capabilities in enabling the customisation of characteristics such as drug dosing, release characteristics and product designs on an individualised basis. Nonetheless, research into 3DP implantable drug delivery devices lags behind that for oral devices, cell-based therapies and tissue engineering applications. The recent efforts and initiatives to address the disparity in women’s health is overdue but should provide a drive for more research into this area, especially using new and emerging technologies as 3DP. Therefore, the focus of this review has been placed on the unique opportunity of formulating personalised implantable drug delivery systems using 3DP for women’s health applications, particularly passive implants. An evaluation of the current landscape and key formulation challenges for achieving this is provided supplemented with critical insight into the current global regulatory status and its outlook

Microfluidics for studying metastatic patterns of lung cancer

The incidence of lung cancer continues to rise worldwide. Because the aggressive metastasis of lung cancer cells is the major drawback of successful therapies, the crucial challenge of modern nanomedicine is to develop diagnostic tools to map the molecular mechanisms of metastasis in lung cancer patients. In recent years, microfluidic platforms have been given much attention as tools for novel point-of-care diagnostic, an important aspect being the reconstruction of the body organs and tissues mimicking the in vivo conditions in one simple microdevice. Herein, we present the first comprehensive overview of the microfluidic systems used as innovative tools in the studies of lung cancer metastasis including single cancer cell analysis, endothelial transmigration, distant niches migration and finally neoangiogenesis. The application of the microfluidic systems to study the intercellular crosstalk between lung cancer cells and surrounding tumor microenvironment and the connection with multiple molecular signals coming from the external cellular matrix are discussed. We also focus on recent breakthrough technologies regarding lab-on-chip devices that serve as tools for detecting circulating lung cancer cells. The superiority of microfluidic systems over traditional in vitro cell-based assays with regard to modern nanosafety studies and new cancer drug design and discovery is also addressed. Finally, the current progress and future challenges regarding printable and paper-based microfluidic devices for personalized nanomedicine are summarized.publishedVersio

The Boston University Photonics Center annual report 2014-2015

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2014-2015 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This has been a good year for the Photonics Center. In the following pages, you will see that the center’s faculty received prodigious honors and awards, generated more than 100 notable scholarly publications in the leading journals in our field, and attracted $18.6M in new research grants/contracts. Faculty and staff also expanded their efforts in education and training, and were awarded two new National Science Foundation– sponsored sites for Research Experiences for Undergraduates and for Teachers. As a community, we hosted a compelling series of distinguished invited speakers, and emphasized the theme of Advanced Materials by Design for the 21st Century at our annual symposium. We continued to support the National Photonics Initiative, and are a part of a New York–based consortium that won the competition for a new photonics- themed node in the National Network of Manufacturing Institutes. Highlights of our research achievements for the year include an ambitious new DoD-sponsored grant for Multi-Scale Multi-Disciplinary Modeling of Electronic Materials led by Professor Enrico Bellotti, continued support of our NIH-sponsored Center for Innovation in Point of Care Technologies for the Future of Cancer Care led by Professor Catherine Klapperich, a new award for Personalized Chemotherapy Through Rapid Monitoring with Wearable Optics led by Assistant Professor Darren Roblyer, and a new award from DARPA to conduct research on Calligraphy to Build Tunable Optical Metamaterials led by Professor Dave Bishop. We were also honored to receive an award from the Massachusetts Life Sciences Center to develop a biophotonics laboratory in our Business Innovation Center

ELUCIDATING MECHANISMS OF METASTASIS WITH IMPLANTABLE BIOMATERIAL NICHES

Metastasis is the leading cause of cancer related deaths, yet it remains the most poorly understood aspect of tumor biology. This can be attributed to the lack of relevant experimental models that can recapitulate the complex and lengthy progression of metastatic relapse observed in patients. Mouse models have been widely used to study cancer, however they are critically limited to study metastasis. Most models generate aggressive metastases in the lung without the use of unique cell lines or specialized injection techniques. This limits the ability to study disseminated tumor cells (DTCs) in other relevant metastasis prone tissues. Prolonged observation of the post-dissemination phase of cancer cell biology and the dormant-to-active transition are additional challenges to study in mouse models due to the rapid onset of actively growing primary and secondary tumors that shorten the experimental timeframe. These limitations have left a critical gap in the understanding of metastasis, specifically the long-term bi-directional crosstalk between DTCs and their local microenvironment. Previous findings have demonstrated that subcutaneously implanted inverted colloidal crystal (ICC) hydrogel scaffolds recruit circulating tumor cells and capture metastatic progression. Here, I introduce new implantable tissue engineered metastasis models that overcome the fundamental restrictions of existing mouse models and substantiate the role of the tumor niche in the reactivation of dormant DTCs with molecular and cellular detail. Throughout my dissertation work I engineered DTC niches leveraging ICC scaffolds to identify critical niche components that enable metastatic progression. Changing the anatomical location of the implant yielded unique microenvironments with varying levels of metastatic potential. In a secondary approach, I utilized the immunomodulatory properties of ICC scaffolds to assist the transplantation of adult lung and liver tissues into the subcutaneous space for prolonged study of metastasis-relevant tissues. Next, I leveraged the transplantable nature of scaffold niches to investigate DTC dormancy and potential triggers of metastatic relapse. I developed a fully humanized mouse model to explore local niche evolution as human DTCs progress from single cells to small colonies and overt metastases. The local vasculature and Ly6G+ cells were observed to play important roles during each step of the transition to aggressive proliferation. The effect of adjuvant chemotherapy and surgical disruption on DTCs and their niche was also explored by using a fully immunocompetent mouse model. Lastly, I improved the fabrication of ICC hydrogel scaffolds to make the process more scalable for widespread use. The use of expanded polystyrene beads enabled cheaper, faster, and safer production of ICC hydrogel scaffolds. Tissue engineering approaches to recreate in vivo DTC microenvironments represent an exciting opportunity to better understand metastasis. The presented models and techniques may be enabling tools to aid in the development of anti-metastasis therapies that significantly benefit patient health

The Boston University Photonics Center annual report 2014-2015

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2014-2015 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This has been a good year for the Photonics Center. In the following pages, you will see that the center’s faculty received prodigious honors and awards, generated more than 100 notable scholarly publications in the leading journals in our field, and attracted $18.6M in new research grants/contracts. Faculty and staff also expanded their efforts in education and training, and were awarded two new National Science Foundation– sponsored sites for Research Experiences for Undergraduates and for Teachers. As a community, we hosted a compelling series of distinguished invited speakers, and emphasized the theme of Advanced Materials by Design for the 21st Century at our annual symposium. We continued to support the National Photonics Initiative, and are a part of a New York–based consortium that won the competition for a new photonics- themed node in the National Network of Manufacturing Institutes. Highlights of our research achievements for the year include an ambitious new DoD-sponsored grant for Multi-Scale Multi-Disciplinary Modeling of Electronic Materials led by Professor Enrico Bellotti, continued support of our NIH-sponsored Center for Innovation in Point of Care Technologies for the Future of Cancer Care led by Professor Catherine Klapperich, a new award for Personalized Chemotherapy Through Rapid Monitoring with Wearable Optics led by Assistant Professor Darren Roblyer, and a new award from DARPA to conduct research on Calligraphy to Build Tunable Optical Metamaterials led by Professor Dave Bishop. We were also honored to receive an award from the Massachusetts Life Sciences Center to develop a biophotonics laboratory in our Business Innovation Center

Implantable Microsystem Technologies For Nanoliter-Resolution Inner Ear Drug Delivery

Advances in protective and restorative biotherapies have created new opportunities to use site-directed, programmable drug delivery systems to treat auditory and vestibular disorders. Successful therapy development that leverages the transgenic, knock-in, and knock-out variants of mouse models of human disease requires advanced microsystems specifically designed to function with nanoliter precision and with system volumes suitable for implantation. The present work demonstrates a novel biocompatible, implantable, and scalable microsystem consisted of a thermal phase-change peristaltic micropump with wireless control and a refillable reservoir. The micropump is fabricated around a catheter microtubing (250 μm OD, 125 μm ID) that provided a biocompatible leak-free flow path while avoiding complicated microfluidic interconnects. Direct-write micro-scale printing technology was used to build the mechanical components of the pump around the microtubing directly on the back of a printed circuit board assembly. In vitro characterization results indicated nanoliter resolution control over the desired flow rates of 10–100 nL/min by changing the actuation frequency, with negligible deviations in presence of up to 10× greater than physiological backpressures and ±3°C ambient temperature variation. A biocompatibility study was performed to evaluate material suitability for chronic subcutaneous implantation and clinical translational development. A stand-alone, refillable, in-plane, scalable, and fully implantable microreservoir platform was designed and fabricated to be integrated with the micropump. The microreservoir consists two main components: a cavity for storing the drug and a septum for refilling. The cavity membrane is fabricated with thin Parylene-C layers, using a polyethylene glycol (PEG) sacrificial layer. The septum thickness is minimized by pre-compression down to 1 mm. The results of in vitro characterization indicated negligible restoring force for the optimized cavity membrane and thousands of punctures through the septum without leakage. The micropump and microreservoir were integrated into microsystems which were implanted in mice. The microtubing was implanted into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion. The results match with syringe pump gold standard. For the first time a miniature and yet scalable microsystem for inner ear drug delivery was developed, enabling drug discovery opportunities and translation to human

Novel technologies in the treatment and monitoring of advanced and relapsed epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death in females in the UK. It has long been recognized to be a set of heterogeneous diseases, with high grade serous being the most common subtype. The majority of patients with EOC present at an advanced stage (FIGO III–IV), and have the largest risk for disease recurrence from which a high percentage will develop resistance to chemotherapy. Despite continual advances in diagnostics, imaging, surgery and treatment of EOC, there has been little variation in the survival rates for patients with EOC. In this review we will introduce novel bioengineering advances in modelling the lymphatic system and real-time tissue monitoring to improve the clinical and therapeutic outcome for patients with EOC. We discuss the advent of the non-invasive 'liquid biopsy' in the surveillance of patients undergoing treatment and follow-up. Finally, we present new bioengineering advances for palliative care of patients to lessen symptoms of patients with ascites and improve quality of life