Search

The use of nanoformulations in drug delivery has a significant impact to increase the drug therapeutic efficacy and improve their safety in anticancer treatments. Non-ionic surfactant vesicles (NSVs), or niosomes, are a class of nanocarriers that are low-cost, physiochemical stable, and represent a promising alternative to liposomes. Tumor-penetrating C-end Rule (CendR) peptides, that target neuropilin-1 (NRP-1), a cell surface receptor commonly overexpressed on solid tumor cells, are widely used for precise delivery of diagnostic and therapeutic nanoparticles to malignant lesions. In this study, we investigated the impact of NSV functionalization with prototypic CendR peptide RPARPAR (abbr. RPAR) on NRP-1-dependent targeting of prostate cancer cells. Doxorubicin (DOX)-loaded NSVs, with or without RPAR conjugation, were prepared, physicochemical characterized, and finally tested for NRP-1 binding in human primary prostate carcinoma-1 and prostate carcinoma epithelial cell lines (PPC-1 and 22Rv1, respectively) that are NRP-1 positive, and melanoma (M21) cells that are NRP-1 negative. We demonstrated that the cellular uptake of RPAR-NSVs was NRP-1-dependent and the uptake rate of RPAR-NSVs was ca. ten times higher than un-targeted NSVs in PPC-1 cells; while no significant differences, between targeted and un-targeted nanocarriers, were obtained in M21 cell line. These data were further confirmed by using NRP-1 CendR-binding pocket-blocking (mAb7E8) antibody, which significantly inhibited the internalization of RPAR-NSVs in PPC-1 cells from ca. 80%–3%. The resulting data obtained of cytotoxic studies agreed the uptake results, thus showing a significant increase of cytotoxic effect for RPAR-NSVs@DOX in PPC-1 and 22Rv1 cells compared to NSVs@DOX. These results provide a proof of concept that the conjugation of CendR peptides on the surface of NSVs can increase the specific targeting of nanoparticles in NRP-1 positive cells, thus improving the therapeutic efficacy of resulting targeted nanocarriers for cancer treatment. Our results have important implications for the development of more efficient and selective cancer therapies and support further in vivostudies by using more complex targeting peptides, such as iRGD or other CendR peptides, that are also targeting primary recruitment receptors (i.e. integrins) and are then proteolytically activated into CendR peptides in the tumor microenvironment.

ABSTRACTIntroduction: New frontiers in nanomedicine are moving towards the research of new biomaterials. Apoferritin (APO), is a uniform regular self-assemblies nano-sized protein with excellent biocompatibility and a unique structure that affords it the ability to stabilize small active molecules in its inner core.Areas covered: APO can be loaded by applying a passive process (mainly used for ions and metals) or by a unique formulative approach based on disassemby/reassembly process. In this article, we aim to organize the experimental evidence provided by a number of studies on the loading, release and targeting. Attention is initially focused on the most investigated antineoplastic drug and contrast agents up to the most recent application in gene therapy.Expert opinion: Various preclinical studies have demonstrated that APO improved the potency and selectivity of some chemotherapeutics. However, in order to translate the use of APO into therapy, some issues must be solved, especially regarding the reproducibility of the loading protocol used, the optimization of nanocarrier characterization, detailed understanding of the final structure of loaded APO, and the real mechanism and timing of drug release.

Microencapsulated curcumin (CUR) was obtained by coevaporation with polymethacrylate polymers (blends at various percent ratios of Eudragit®RS100 and RL100 resins). The suspensions were freeze-dried to produce free flowing microparticles, which were sieved in the 420–90 μm range. They were characterized in the solid state for micromeritic properties and drug loading, and by FT-IR, powder X-ray diffractometry and differential scanning calorimetry for physical state. Encapsulation efficiency largely varied from 35 to 95%, mainly depending on the copolymer composition and to a less extent from drug-to-polymer ratio. Solid-state characterization confirmed the chemical stability of CUR in microparticles, and suggested that the drug was in a microcrystalline form within the polymer matrix; microscopy analysis confirmed the latter statement. In vitro release and dissolution profile of neat and encapsulated CUR were assessed in simulated gastric and intestinal fluids: from these studies, it was however found that the microencapsulation of CUR in these polymers did not improve the solubility of this very poorly soluble compound in simulated gastric and intestinal aqueous media.

Drug delivery to the brain represents one of the most important challenges in the field of nanomedicine, as the study and planning of nanocarriers able to cross the blood brain barrier are topics at the cutting edge of technology and innovation. In this review, we analyze the interventions and progresses in the field, by analyzing the choice of the polymer, of the ligands and the main relevant in vivoand in vitroexperiments. A critical overview of these aspects will help in better understanding the status of nanomedicine in the application to central nervous system pathologies along with the future directions.

A dyshomeostasis of zinc ions has been reported for many psychiatric and neurodegenerative disorders including schizophrenia, attention deficit hyperactivity disorder, depression, autism, Parkinson's and Alzheimer's disease. Furthermore, alterations in zinc-levels have been associated with seizures and traumatic brain injury. Thus, altering zinclevels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. However, given the restriction of zinc uptake into the brain by the blood-brain barrier, methods for controlled regulation and manipulation of zinc concentrations within the brain are rare. Here, we performed in vivo studies investigating the possibility of brain targeted zinc delivery using zinc-loaded nanoparticles which are able to cross the blood-brain barrier. After injecting these nanoparticles, we analyzed the regional and time-dependent distribution of zinc and nanoparticles within the brain. Moreover, we evaluated whether the presence of zinc-loaded nanoparticles alters the expression of zinc sensitive genes and proteins such as metallothioneins and zinc transporters and quantified possible toxic effects. Our results show that zinc loaded g7 nanoparticles offer a promising approach as a novel non - invasive method to selectively enrich zinc in the brain within a small amount of time.

This editorial provides an overview of the main advantages of the use of nanomedicine-based approach for innovation in the treatment of neurodegenerative diseases. Besides these aspects, a critical analysis on the main causes that slow the application of nanomedicine to brain disorders is given along with the identification of possible solutions and possible interventions. Better communication between the main players of research in this field and a detailed understanding of the most critical issues to be addressed should help in defining future directions towards the improvement and, finally, the clinical application of nanomedicine to neurodegenerative diseases.

Introduction:Nanocarriers are considered to be one of the most innovative drug delivery systems, owing to their high potential in drug protection, delivery and targeting to the diseased site. Unfortunately, their applicability is hampered mainly by their uptake, due to macrophagic recognition and lack of specificity, if not properly engineered.Areas covered:Sialic acid (SA) and its derivatives have recently been studied in order to govern their stealthness as carriers and their effectiveness as targeting moieties. In this review, the most outstanding research (in vitroand in vivo) dealing with the use of SA or its derivatives to modify the surface carriers, in order to achieve targeted or stealth nanosystems, is summarized. Moreover, the application of SA or its derivatives as modifiers in cancer targeting and therapy, and in recognition purposes, is considered.Expert opinion:The application of SA-based strategies for nanocarrier engineering represents one of the most stimulating challenges in drug delivery and drug targeting. Both in vivoand in vitroresults on stealth or targeted nanocarriers, modified with different kinds of SA or SA derivative, have highlighted the great potential of this approach. These studies have drawn attention to both the advantages (stealth properties, targeting ability, cancer inhibition, viral and inflammation recognition, brain targeting) and the possible disadvantages (i.e., presence of possible multi-target side effect outputs) of this strategy, and overall suggests that further investigations on this strategy are required.

Nanoparticles (Np) and liposomes (L) were engineered obtaining selective drug delivery systems able to cross BBB and to treat cancer diseases, respectively. The first goal was achieved conjugating a specific epta-glucopeptide (g7) to polymeric nanoparticles (Np). The data related the nociceptive activity showed the ability of g7-Np to cross the BBB and to release loperamide in the brain. To reach the second goal we have recently proposed the immunoliposomes (ILp) for tumor-targeted delivery of gene material (particularly SiRNAs), which are selected in vitro for the specific antineoplastic activity against herpesvirus-associated B-cell lymphomas, particularly HHV8+ Primary Effusion Lymphoma (PEL). In the preliminary study we have prepared and characterized the ILp direct to PEL cells (BCBL-1 cell line). The cellular trafficking of the encapsulated model FITC-ODN obtained by flow cytometry and confocal microscopy was evaluated by the ability of the new carriers to selectively interact with cells. The data were compared with the different behaviour of these liposomes respect to the un-targeted cationic and pegylated liposomes.

Background: Nanoparticulate polymeric systems (nanoparticles [Np]) have been widely studied for the delivery of drugs to a specific target site. This approach has been recently considered for the therapy of brain diseases. The major problem in accessing the CNS is linked to the presence of the blood–brain barrier. Objective: The present review deals with the different strategies that have been developed in order to allow Np drug carriers entry into the CNS parenchyma. Among these, the use of magnetic Np, Np conjugation with ligands for blood–brain barrier receptors, with antibodies, and the use of surfactants have been considered. Methods: All the literature available is reviewed in order to highlight the potential of this drug delivery system to be used as a drug carrier for the treatment of CNS pathologies. Conclusions: Polymeric Np have been shown to be promising carriers for CNS drug delivery due to their potential both in encapsulating drugs, hence protecting them from excretion and metabolism, and in delivering active agents across the blood–brain barrier without inflicting any damage to the barrier. Different polymers have been used and different strategies have been applied; among these, the use of specific ligands to enhance the specificity of drugs delivered to the CNS has recently been considered. At present, clinical trials are being conducted appeared for the use of these drug carriers but none related to the treatment of CNS diseases.

Nanoparticles (Np) and liposomes (L) were engineered obtaining selective drug delivery systems able to cross BBB and to treat cancer diseases, respectively. The first goal was achieved conjugating a specific epta-glucopeptide (g7) to polymeric nanoparticles (Np). The data related the nociceptive activity showed the ability of g7-Np to cross the BBB and to release loperamide in the brain. To reach the second goal we have recently proposed the immunoliposomes (ILp) for tumor-targeted delivery of gene material (particularly SiRNAs), which are selected in vitro for the specific antineoplastic activity against herpesvirus-associated B-cell lymphomas, particularly HHV8+ Primary Effusion Lymphoma (PEL). In the preliminary study we have prepared and characterized the ILp direct to PEL cells (BCBL-1 cell line). The cellular trafficking of the encapsulated model FITC-ODN obtained by flow cytometry and confocal microscopy was evaluated by the ability of the new carriers to selectively interact with cells. The data were compared with the different behaviour of these liposomes respect to the un-targeted cationic and pegylated liposomes.

ABSTRACTWhile the role of the blood-brain barrier (BBB) is increasingly recognized in the (development of treatments targeting neurodegenerative disorders, to date, few strategies exist that enable drug delivery of non-BBB crossing molecules directly to their site of action, the brain. However, the recent advent of Nanomedicines may provide a potent tool to implement CNS targeted delivery of active compounds. Approaches for BBB crossing are deeply investigated in relation to the pathology: among the main important diseases of the CNS, this review focuses on the application of nanomedicines to neurodegenerative disorders (Alzheimer, Parkinson and Huntington's Disease) and to other brain pathologies as epilepsy, infectious diseases, multiple sclerosis, lysosomal storage disorders, strokes.

The interaction of diclofenac sodium salt (DCFNa) and two cyclodextrins, β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD), studied in D2O solution with different NMR techniques (1H, 13C NMR, ROESY experiments, NMR titrations), shows the existence of multiple equilibria involving 1:1 and 2:1 guest–host complexes.

The interaction of diclofenac sodium salt (DCFNa) and two cyclodextrins, β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD), studied in D2O solution with different NMR techniques (1H, 13C NMR, ROESY experiments, NMR titrations), shows the existence of multiple equilibria involving 1:1 and 2:1 guest–host complexes.