Current Organic Chemistry - Volume 21, Issue 1, 2017

Several kinds of polymeric particles designed for drug delivery purposes can be successfully synthesized via heterogeneous polymerization processes. Due to the high ability to produce tailor-made polymers, suspension, mass-suspension, suspension-emulsion, miniemulsion and emulsion polymerization processes deserve special attention in the drug delivery field, as the process operating conditions play a significant role on both the morphology and the macromolecular architecture of the polymeric materials. The present paper also focuses on the main features of important polymer system used in drug delivery, as well as, the cancer therapy, exploring the receptor-based targeting of therapeutics and the cancer recognition mechanisms given special attention to the combined action of immunotherapy and chemotherapy. Dissolution models are also discussed due to their importance to the prediction of the dissolution process and drug release in the blood, providing fundamental insight into the dissolution profiles of the drug along the treatment time.

Targeted drug delivery is a new multidisciplinary field that aims to develop innovative nanomaterials, tools and devices to deploy a therapeutic agent to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. Advanced drug-delivery systems attempt to control the site of action and release rate and act by means of either a physiological or a chemical trigger. In this sense, stimuliresponsive biomaterials are of special interest for application as components of drug-delivery devices. This review discusses the use of elastin-like recombinamers (ELR) in drug-delivery systems. These biopolymers possess special properties that encompass biodegradability, bioactivity and stimuli-responsiveness. Their tailormade design using recombinant DNA technologies allows an absolute control of their amino acid sequence and design of the most appropriate macromolecule for each application. Firstly, devices based on monomeric elastinlike recombinamers which have been chemically modified to attach functionalities that enable us to follow or direct their distribution or anticancer drugs in an attempt to improve drug-conjugate uptake are described. Secondly, ELRs that form part of nanoparticles as drug carriers will be studied in their different versions, including nanoparticles chemically reinforced by interchain cross-linking, nanoparticles formed by self-assembly of chemically modified ELRs to achieve amphiphilic properties and multifunctional composites made up of nanoparticles coated with ELRs. Finally, recent advances in the area of 3D platforms for drug delivery, comprising interconnected hydrogels and ELR-based coacervates in the form of depots, will be reviewed.

Cancer is a serious hazard to human health all around the world; however, many current therapies remain toxic and poor. In view of the understanding of immunology and tumor biology, cancer immunotherapy with minimal toxicity has been regarded as a promising strategy for cancer treatment because of immune surveillance. Unfortunately, the efficacy of immunotherapy was impeded and resisted due to the tumor immune evasion mechanism. Hence, targeted cancer immunotherapy has been proposed to tackle the tumor immune suppression and complexity of malignant tumor cells. Nanotechnology-based immunotherapy has improved the limitations and enhanced the therapeutic efficiency of traditional immunotherapy. This review illustrates the recent progresses in immunotherapy based on nanotechnology, and reveals that nanodevices could be utilized for active and passive cancer immunotherapy.

Despite the increasing number of natural and synthetic antimicrobial agents, the prevalence of severe infections, produced by antibiotic resistant pathogens or involving biofilm embedded bacteria continues to emerge. Although antibiotics are still the only choice for treating infections, either in unique or in combined therapeutic schemes, a series of limitations related to the physico-chemical properties of the drug, the host response and the particularities of the infectious agent should be surpassed. A great contribution is brought by the recent advances made on the nanotechnological field regarding the development of efficient drug delivery systems. Nanostructurated shuttles for the targeted, prolonged and controlled release of antibiotics are increasing their therapeutic efficiency, while reducing the required active doses and consequently the adverse effects on the host. This review highlights the main types of nanostructures used for improving the efficiency of antibiotics active against difficult to treat infections, such as those caused by resistant strains, biofilms and intracellular bacteriae.

This article offers a review regarding current approaches in bioactive dressings design, the bioactive components as well as the experimental models used to assess their efficiency. Wound dressings come in a variety of materials including natural polymers and synthetic polymers manufactured into various forms, such as foams, films, hydrocolloids, hydrogels, sponges, membranes, skin substitutes, electrospun micro and nanofibers. Until now there is no available dressing able to meet the criteria for a fast and adequate wound healing. The dressing material may have intrinsic wound healing activity or/and may serve as a support for the release of bioactive compounds such as antimicrobial agents (antibiotics, antiseptics, honey, plant extracts), growth factors, insulin. There are a lot of controversies regarding the use of antimicrobials in the wounds management. However non - antibiotic antibacterial treatment regiments are a must due to alarming antibiotic resistance. Most of the developed bioactive wound dressings were not tested on human patients, and may prove not applicable in clinical settings. Therefore, appropriately designed clinical studies are necessary to establish the safety profile and the efficacy of novel bioactive dressings, in terms of ease of use, cost-effectiveness and patient satisfaction, combined with in depth fundamental research of the mechanisms of action of different dressing's components.

Inevitable caries formation and other tooth related diseases are one of the most common factors affecting human quality of life, as they are often followed by loss of teeth. Significant research efforts have been devoted to establishing control and preventive solutions. It is clearly known that fluoride is one of the promising chemical substances with anti-carious activity. The elimination of the microbial infection, especially the multispecies infections induced by aerobic and anaerobic bacteria, is a current challenge of the endodontic therapy. Using antibiotics or other active agents (from ions, nanoparticles to natural products) loaded in specific drug carrier systems seems to be ideal approach in treating and controlling dental diseases, even if, the drug delivery systems used in dental applications are less established comparing with other tissues/organs. Based on the importance of biomedical drug delivery systems the present study aims to give a brief review on the improvements of drug delivery systems for dental applications.

Hemoglobinopathies, such as β-thalassemia and sickle cell disease (SCD), are among the most common congenital diseases in the world, with high mortality and morbidity rates. The most straightforward approach to correct the main culprit in hemoglobinopathies - the imbalance between the amounts of alpha-like globins/betalike globins- will need to target directly the gene structure or their regulatory elements in order to obtain a sustained therapeutic effect. Finding effective methods to deliver the genetic “blueprints” of the correct and functional protein or, even better, the “DNA repairing kit” able to do the job in situ, remains a major challenge, despite the fact that gene therapy is already used in different diseases. Members of several viral families were employed as “Trojan horses” using the virus ability to deliver a modified genetic material inside the cell and to manipulate the host replication machinery to produce the encoded proteins. Recently, non-viral vectors are gaining advantages for genome correction, especially after the exponential development of the genome editing approaches that can provide precise in situ modifications. This review summarizes the recent advances in the viral and non-viral delivery strategies and emphasizes the therapeutic potential of different approaches designed to correct the genetic defects responsible for the most common hemoglobinopathies.

This review presents possible routs of preparation of acridine derivatives con-taining saturated rings that can be obtained both as a result of traditional organic synthesis based on cyclization and condensation reactions and whenever available by partial or total catalytic (heterogeneous or homogeneous) hydrogenation of appropriate acridine derivatives. Methods of preparations of acridine derivatives bearing saturated rings are presented and discussed. The influence of resonance stabilisation energies of N-heteroaromatic and partly saturated N-heteroaromatic structures on hydrogenation susceptibility is discussed in relation to other aspects influencing saturation N-heteroaromatic versus carbocyclic rings.