Summary Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.

Type 1 diabetes

Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer.

Nanotechnology has been extensively studied and exploited for cancer treatment as nanoparticles can play a significant role as a drug delivery system. Compared to conventional drugs, nanoparticle-based drug delivery has specific advantages, such as improved stability and biocompatibility, enhanced permeability and retention effect, and precise targeting. The application and development of hybrid nanoparticles, which incorporates the combined properties of different nanoparticles, has led this type of drug-carrier system to the next level. In addition, nanoparticle-based drug delivery systems have been shown to play a role in overcoming cancer-related drug resistance. The mechanisms of cancer drug resistance include overexpression of drug efflux transporters, defective apoptotic pathways, and hypoxic environment. Nanoparticles targeting these mechanisms can lead to an improvement in the reversal of multidrug resistance. Furthermore, as more tumor drug resistance mechanisms are revealed, nanoparticles are increasingly being developed to target these mechanisms. Moreover, scientists have recently started to investigate the role of nanoparticles in immunotherapy, which plays a more important role in cancer treatment. In this review, we discuss the roles of nanoparticles and hybrid nanoparticles for drug delivery in chemotherapy, targeted therapy, and immunotherapy and describe the targeting mechanism of nanoparticle-based drug delivery as well as its function on reversing drug resistance.

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Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance

Direct delivery of proteins into cells avoids many drawbacks of gene delivery, and thus has emerging applications in biotherapy. However, it remains a challenging task owing to limited charges and relatively large size of proteins. Here, we report an efficient protein delivery system via the co-assembly of fluoroamphiphiles and proteins into nanoparticles. Fluorous substituents on the amphiphiles play essential roles in the formation of uniform nanoparticles, avoiding protein denaturation, efficient endocytosis, and maintaining low cytotoxicity. Structure-activity relationship studies reveal that longer fluorous chain length and higher fluorination degree contribute to more efficient protein delivery, but excess fluorophilicity on the polymer leads to the pre-assembly of fluoroamphiphiles into stable vesicles, and thus failed protein encapsulation and cytosolic delivery. This study highlights the advantage of fluoroamphiphiles over other existing strategies for intracellular protein delivery.

The fluorination effect of fluoroamphiphiles in cytosolic protein delivery.

The unique combination of mechanical, optical and electrical properties offered by carbon nanotubes has fostered research for their use in many kinds of applications, including the biomedical field. However, due to persisting outstanding questions regarding their potential toxicity when considered as free particles, the research is now focusing on their immobilization on substrates for interface tuning or as biosensors, as load in nanocomposite materials where they improve both mechanical and electrical properties or even for direct use as scaffolds for tissue engineering. After a brief introduction to carbon nanotubes in general and their proposed applications in the biomedical field, this review will focus on nanocomposite materials with hydrogel-based matrices and especially their potential future use for diagnostics, tissue engineering or targeted drug delivery. The toxicity issue will also be briefly described in order to justify the safe(r)-by-design approach offered by carbon nanotubes-based hydrogels.

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Overview of Carbon Nanotubes for Biomedical Applications

With increasing importance of nanoparticles in pharmaceutical applications, it is desirable that researchers from a wide variety of disciplines become involved to recognize the nature of the often-unexpected challenges associated with synthesis and characterization of nanoparticles, including the difficulties of maintaining desired material properties during handling and processing due to their dynamic nature. Nanoparticles behave differently as the particle size becomes dramatically reduced with respect to the bulk. Nanoparticles’ physical and chemical properties have a high impact on their molecular biology and systemic activities. Therefore, it is necessary to characterize nanoparticles’ physicochemical properties (particle size, shape, structure, chemistry, crystallography, etc.) to qualify nanoparticles for use in pharmaceutical applications. This chapter aims to elaborate on the various characterization parameters used to determine the characteristics of nanoparticles including size, shape, surface morphology, surface charge, biocompatibility, crystallinity, flow characteristics, hygroscopicity, rheology, magnetic properties, porosity, and optical properties.

Importance of Physicochemical Characterization of Nanoparticles in Pharmaceutical Product Development

'Dendrimer-Cationized-Albumin' encrusted polymeric nanoparticle improves BBB penetration and anticancer activity of doxorubicin.

Nanogold-core multifunctional dendrimer for pulsatile chemo-, photothermal- and photodynamic- therapy of rheumatoid arthritis.

The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

Nidhi Raval

Papers

Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer.

Importance of Physicochemical Characterization of Nanoparticles in Pharmaceutical Product Development

'Dendrimer-Cationized-Albumin' encrusted polymeric nanoparticle improves BBB penetration and anticancer activity of doxorubicin.

Nanogold-core multifunctional dendrimer for pulsatile chemo-, photothermal- and photodynamic- therapy of rheumatoid arthritis.

Carbon nanotubes (CNTs) based advanced dermal therapeutics: current trends and future potential