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Among various types of stimuli-responsive drug delivery systems, reduction-responsive polymers have attracted great interest. In general, these systems have high stability in systemic circulation, however, they can respond quickly to differences in the concentrations of reducing species in specific physiological sites associated with a pathology. This is a particularly relevant strategy to target diseases in which hypoxic regions are present, as polymers which are sensitive to in-situ expressed antioxidant species can, through a local response, release a therapeutic at high concentration in the targeted site, and thus, improve the selectivity and efficacy of the treatment. At the same time, such reduction-responsive materials can also decrease the toxicity and side effects of certain drugs. To date, polymers containing disulfide linkages are the most investigated of the class of reduction-responsive nanocarriers, however, other groups such as selenide and diselenide have also been used for the same purpose. In this review article, we discussed the rationale behind the development of reduction-responsive polymers as drug delivery systems and highlight examples of recent progress. We include the most popular design methods to generate reduction-responsive polymeric carriers and their applications in cancer therapy, and question what areas may still need to be explored in a field with already a very large number of research articles. Finally, we consider the main challenges associated with the clinical translation of these nanocarriers and the future perspectives in this area. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies., (© 2020 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

The aim of this work was to investigate the potential of small nanoparticles (NPs) made of a poly(ethylene glycol)-poly(ε-caprolactone)-amphiphilic diblock copolymer (PEG-b-PCL, PEG=2kDa and PCL=4.2kDa) as drug carrier system through the skin. Zinc(II) phthalocyanine (ZnPc), selected as lipophilic and fluorescent model molecule, was loaded inside NPs by a melting/sonication procedure. Loaded NPs with a hydrodynamic diameter around 60nm, a slightly negative zeta potential and a ZnPc entrapment dependent on polymer/ZnPc ratio were obtained. Spectroscopic investigations evidenced that ZnPc was entrapped in monomeric form maintaining its emission properties. The transport of ZnPc through porcine ear skin was evaluated on Franz-type diffusion cells after treatment with different vehicles (water or PEG 0.4kDa) containing free ZnPc or ZnPc-loaded NPs without and with (2-hydroxypropyl)-β-cyclodextrin (HPβCD) as permeation enhancer. Independently of the sample tested, ZnPc was transported in the skin without reaching receptor compartment. On the other hand, ZnPc was found in the skin in large amount and also in the viable epidermis when delivered through NPs associated with HPβCD, especially in conditions limiting water evaporation. Fluorescence images of skin samples after 24h of permeation were in line with ZnPc dosage in the skin and demonstrated the ability of NPs covalently tagged with rhodamine to penetrate the skin and to locate in the intercellular spaces. Insight into skin chemical properties upon application of NPs by confocal Raman spectroscopy demonstrated that HPβCD caused an alteration of water profile in the skin, highly reducing the degree of hydration at stratum corneum/viable epidermis interface which can promote NP transport. Taken together, these results highlight PEG-b-PCL NPs coupled with HPβCD as a novel vehicle for the skin delivery of highly lipophilic compounds paving the way to several applications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: The application of nanotechnologies to the cancer field for therapeutic, imaging or diagnostic purposes represents an advanced and very attractive approach to overcome the main limits related to conventional chemotherapy. In particular, core-shell nanocarriers can be engineered to provide adequate features to overcome the main biological barriers encountered by free anti-cancer drugs., Areas Covered: This review will try to summarise the design rules - as dictated by biological requirements - to take into account for proper nanocarrier design and to highlight the potential of administration routes other than intravenous., Expert Opinion: Although intravenous injection remains the most investigated route of administration for 'nanoncologicals', research interest towards less explored administration routes allowing localised chemotherapy or delivery in close proximity to the tumour site might change the way cancer is treated in the near future. Nevertheless, an experimental set-up more biologically oriented taking into account an in-depth evaluation of stability in complex media, protein interaction, and cell interaction of novel nanoconstructs could allow their successful translation in pre-clinical and clinical settings.

Several PEGylated polyester-based nanoncologicals have been proposed in the literature, some of them nowadays being under preclinical/clinical trials or marketed. In this review, we describe the main features of PEGylated polyesters and their correspondent nanocarriers. A first part is devoted to intravenously injectable PEGylated nanocarriers, which represent the systems most investigated so far. After describing fundamental design rules dictated by the administration route, PEGylated nanocarriers currently under preclinical/clinical investigation or in the market will be described from a technological point of view and related therapeutic implications discussed. Finally, new perspective of use of PEGylated nanocarriers for oral and pulmonary delivery of anticancer drugs will be considered.

Effective delivery of tumor antigens to APCs is one of the key steps for eliciting a strong and durable immune response to tumors. Several cancer vaccines have been evaluated in clinical trials, based on soluble peptides, but results have not been fully satisfactory. To improve immunogenicity particles provide a valid strategy to display and/or incorporate epitopes which can be efficiently targeted to APCs for effective induction of adaptive immunity. In the present review, we report some leading technologies for developing particulate vaccines employed in cancer immunotherapy, highlighting the key parameters for a rational design to elicit both humoral and cellular responses.

Abstract: The self‐assembly of specific polymers into well‐defined nanoparticles (NPs) is of great interest to the pharmaceutical industry as the resultant materials can act as drug delivery vehicles. In this work, a high‐throughput method to screen the ability of polymers to self‐assemble into NPs using a picoliter inkjet printer is presented. By dispensing polymer solutions in dimethyl sulfoxide (DMSO) from the printer into the wells of a 96‐well plate, containing water as an antisolvent, 50 suspensions are screened for nanoparticle formation rapidly using only nanoliters to microliters. A variety of polymer classes are used and in situ characterization of the submicroliter nanosuspensions shows that the particle size distributions match those of nanoparticles made from bulk suspensions. Dispensing organic polymer solutions into well plates via the printer is thus shown to be a reproducible and fast method for screening nanoparticle formation which uses two to three orders of magnitude less material than conventional techniques. Finally, a pilot study for a high‐throughput pipeline of nanoparticle production, physical property characterization, and cytocompatibility demonstrates the feasibility of the printing approach for screening of nanodrug delivery formulations. Nanoparticles are produced in the well plates, characterized for size and evaluated for effects on metabolic activity of lung cancer cells. [ABSTRACT FROM AUTHOR]