Current Drug Targets - Volume 19, Issue 4, 2018

Background: Rapid developments in the field of nanoparticles during the last decades have led to its increased application in drug delivery approaches. The advantages of nano-based drug delivery systems include improved therapeutic efficacy of drugs and the reduction of side effects. Objective: This review aims to highlight advances in stimuli-triggered drug delivery approaches using polymeric nanoparticles with a focus on pH-sensitive drug- and theranostic delivery systems. Results and Conclusion: Of the various organic/inorganic nanoparticles, polymeric nanoparticles have fulfilled an integral role in the advancement of drug delivery systems by virtue of the ease to incorporate and modify targeting moieties in combination with controlled drug release over prolonged periods. Furthermore, polymeric nanoparticles facilitate theranostic treatment by the incorporation of imaging agents in addition to therapeutics. Recently, stimuli-responsive polymeric nanoparticles emerged as smart drug carriers, in which drug release is affected by physical and/or chemical structural changes induced by a specific stimulus (e.g. pH, temperature, and specific enzymes). The use of these nanocomposites reduces premature drug release and maintains effective drug levels at the pathological target.

Background: Smart triggered release in controlled drug delivery has met an astonishing interest from the scientific community in the past few years due to the obvious medical benefits this type of systems represents. The reduction in toxicity due to a non-systemic administration is not the only reason for this increase, although it is a major reason for concern typically in anti-cancer therapy, but also the fact that some good therapeutic substances cannot be used either due to their high hydrophobicity or due to a very poor absorption at the required site of delivery. Objective: This review article aims to highlight the efforts made by the scientific community in order to more efficiently trigger the drug payload at its destination, thus avoiding systemic exposure to the drug's toxic effect. Results: In this review article several types of triggers have been evaluated, pH triggered delivery, thermally triggered delivery, REDOX change triggered delivery, as well as modifications made to trigger at a specific location based on the affinity of the receptors for a certain chemical moiety, such as folic acid. Conclusions: Through a proper nano-formulation the obstacles encountered by systemic delivery strategies can be circumvented, and through minor modifications hydrophobic drugs can be delivered through minor modifications to their structure, ensuring in the meantime that the therapeutic form is broken down by the human body's own internal systems. The main advantages in triggered drug delivery are the better healthcare strategy and the topical delivery, the main person winning in this case being the patient, the one person that should always be at the heart of the medical system.

Background: The rapid emergence of nanotechnology and biotechnology has enabled revolutionary developments for drug delivery systems. Recently, drug delivery has attracted extensive research interest; applied to improve the functions of these carriers and their applications. Objective: Active drug delivery is currently approved as an ideal approach for targeted transport in a biological entity and can cooperate with therapeutic mediums in transporting cargoes. Results and conclusion: In this review, several active targeted cargomediated drug delivery patterns have been summarized, including molecular motors, bio-camouflaged particles, and self-propelled nanomotors. Subsequently, a series of active targeted carriers for drug delivery were introduced, and their ability for targeted binding was discussed. Furthermore, the mechanism of active targeted transport was exposited in detail, and some promising works are highlighted.

Background: Despite all the advances achieved in the field of tumor-biology research, in most cases conventional therapies including chemotherapy are still the leading choices. The main disadvantage of these treatments, in addition to the low solubility of many antitumor drugs, is their lack of specificity, which leads to the occurrence of severe side effects due to nonspecific drug uptake by healthy cells. Objective: The purpose of this manuscript is to review and analyze the recent progress made in cancer nanotherapy. Results: Progress in nanotechnology and its application in medicine have provided new opportunities and different smart systems. Such systems can improve the intracellular delivery of the drugs due to their multifunctionality and targeting potential. First, we provide a global overview of cancer and different smart nanoparticles currently used in oncology. Then, we analyze in detail the development of drug-delivery strategies in cancer therapy, focusing mainly on the intravenously administered smart nanoparticles. Finally, we discuss the challenges, clinical trials, marketed nanomedicines and future directions of the nanotherapy applied to cancer treatment. Conclusión: In this review, we have evidenced the tremendous potential that smart drug-delivery systems have to enhance the therapeutic effect of current standard treatment modalities, including chemotherapies and radiotherapies.

Background: Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. Results: ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. Conclusion: Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments.

Background: Ribosome-inactivating proteins (RIPs) are wildly found in multiple species of plants, bacteria and fungi. As a special family of protein toxins, RIPs can inhibit protein synthesis and induce cell death via inactivating ribosome in eukaryotic cells. Thus, RIPs have been applied for anti-tumor therapy in the past two decades. However, because of poor cell permeability, nonselective mode of action for tumor cells, poor pharmacokinetic profiles and immunogenicity, their clinical application has been severely constrained. As an effort to overcome these obstacles, tumor-specific monoclonal antibodies (mAb) have been conjugated to RIPs (forming so called “immunotoxins”) specifically to increase their cytotoxicity and provide tumor targeting. Nevertheless, immunotoxins yet have not fully resolved all the issues and critical challenges still remain, such as immunogenicity and inability to penetrate into the deep site of tumor. Objective: To overcome the constrain of immunotoxins, the novel cell-penetrating peptide (CPP)- modified ATTEMPTS systems based on combination of CPP-mediated penetration and antibodymediated tumor targeting, with triggerable drug release function, were developed to achieve effective and safe delivery of protein toxin. Results: The CPP-modified ATTEMPTS systems showed effective protamine-triggered CPP-toxin release and thus enhanced CPP-mediated cellular uptake and cytotoxicity. It also showed antibodymediated in vivo tumor targeting and significantly increased in vivo tumor growth suppression with limited systematic toxicity. Conclusion: The CPP-modified ATTEMPTS systems were developed and demonstrated as a proof-ofconcept for CPP-based protein toxin delivery with triggerable antibody targeting to improve the druggability of protein toxin drugs. The systems showed the potential application of protein toxin clinical translation in anticancer treatment.

Background: Nanomedicine is currently exploited for manufacturing therapeutic DDS and treatments protocols for various diseases and disorders. To obtain DDS, different types of materials are used, from organic to inorganic, polar to non-polar, micro to nanomaterials from 0D to 3D structured materials, respectively. Many of these materials were extensively studied and reviewed in the literature. Objective: The objectives of this review is to make a clear overview on drug delivery systems depending several aspects related to delivery mechanisms, the type of supports, the active agents ant the potential applications in the prevention or treatment of various diseases. Results: Following aspects are extensively debated: synthesis issues, characteristics and potential uses of 0, 1, 2 and 3D drug delivery systems according to their nature and applications. These systems can be can be tailored according to the delivery mechanism (0-3D delivery) as well as by using more active agents, with more therapeutic activity or same activity but with different mechanisms of action. The size and morphology of the drug delivery system is essential, especially when talking about the internalization into the tumor cells while the mobility is especially dependent on the size. The influence of the nature of the supports and their polarity was extensively studied during the last decades, as well as the importance of the porosity and pore size, but only limited papers are devoted to the holistic analysis of the dimensionality of the support and the ways of delivering the active agents. Conclusion: This review is devoted to a holistic insight into the drug delivery systems, from a new, only marginally studied point of view, meaning the dimensionality of the drug delivery systems and the characteristics of the delivery.