Nanometric Drug Delivery Systems Research Articles

Controlling the protein corona of polymeric nanocapsules: effect of polymer shell on protein adsorption.

Understanding the interactions between nanocarriers and plasma proteins is essential for controlling their biological fate. Based on the reported potential of polymeric nanocapsules (NCs) for the targeted delivery of oncological drugs, the main objective of this work has been to investigate how the surface chemical composition influences their protein corona fingerprint. Thus, we developed six NC prototypes with different polymer shells and physicochemical properties and quantified the amount of protein adsorbed upon incubation in human plasma. Using sequential window acquisition of all theoretical mass spectra (SWATH-MS) and following the Minimum Information about Nanomaterial Biocorona Experiments (MINBE) guidelines, we identified different protein corona patterns. As expected, the presence of polyethylene glycol (PEG) in the polymer shell reduced the protein corona, particularly the adsorption of immunoglobulins. However, by comparing the different prototypes, we concluded that the protein adsorption pattern was not exclusively driven by PEG. In fact, a highly PEGylated prototype exhibited intense apolipoprotein IV adsorption. On the other hand, we also observed that polymeric NCs containing 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) exhibited high adsorption of vitronectin, a protein that is known for enhancing the uptake of nanosystems by lung epithelium and several cancer cells. Overall, the gathered information allowed us to identify promising polymeric NCs with an expected prolonged circulation time, enhanced tumor targeting, liver accumulation, and preferential uptake by the immune system. In this sense, the analyses of the protein corona performed along this work will hopefully contribute to advancing a new generation of rationally designed nanometric drug delivery systems.

Morphogenic effect of common solvent in the self-assembly behavior of amphiphilic PEO-b-PLA

The formation of block copolymer nanoparticles is commonly obtained by switching solvent quality from good solvent for both blocks to a selective solvent for one block. The effect of the selective solvent on particle dimension, shape and inner structure has been analyzed in detail, instead less attention has been focused on the role of the common solvent. Poly(ethylene oxide)-block-poly(lactic acid) (PEO-b-PLA) is widely used for the preparation of nanometric drug delivery systems and the control of the particle morphology has relevant effects on bioactivity. In this work we investigate the effect of using different common solvents (acetone, dioxane, tetrahydrofuran, dimethylformamide) on the self-assembly behavior of narrowly dispersed PEO-b-PLA copolymers, synthesized by metal free ring-opening polymerization, with large variation of molecular weight of the hydrophobic block (from 65 to 1300 lactic units). Dynamic light scattering (DLS) and cryo-electron microscopy (cryo-EM) analyses of PEO-b-PLA nanoparticles reveal that their size and shape are strongly dependent on the hydrogen bonding ability of the common solvent used in the self-assembly process. As consequence of these variations, also the cytoxicity of the nanoparticles is affected.

Application of Abdominal Imaging Based on Nano Drug Delivery System for Diagnosis and Treatment of Liver Cancer.

Liver cancer has a high incidence and a poor prognosis, which seriously affects human health. Doxorubicin is one of the chemotherapeutics used in the treatment of tumours, but its severe adverse reactions, especially cardiac toxicity, have limited its clinical application. The nanometre drug delivery system enables drug-loaded nanoparticles to be specifically concentrated in tumour tissues, increasing cell uptake and improving curative effect. Therefore, in this paper, folic acid-modified mesoporous silica nanoparticles (MSN-NH2-PEG-FA) were synthesized by modifying the folic acid on the surface of a drug carrier by using the characteristics of the expression of folic acid receptors, and using it as a drug. The carrier was loaded with antitumor drug doxorubicin hydrochloride (DOX), and a nanometre drug delivery system (MSN-NH2-PEG-FA/DOX) was constructed. At the same time, the near-infrared dye Cy5 was used to mark the mother nucleus to construct fluorescent nanoparticles (MSN-NH2-PEG-FA/DOX-Cy5) for cell and tumour imaging, so as to obtain the abdominal image of liver cancer patients, thereby realizing diagnosis and treatment. The research results show that the carrier can specifically gather in the liver area, reduce the distribution in the heart, reduce the toxic and side effects of drugs, and prolong the survival time of patients. The results of this study provide new ideas for the treatment of liver cancer, and provide a new theoretical basis and experimental basis for the study of inorganic nanomaterials as targeted drug delivery systems.

More than Just Size: Challenges and Opportunities of Hybrid Dendritic Nanocarriers.

Dendrimers and hyperbranched polymers are emerging polymer architectures that attract increasing attention due to their unique topological structure and interesting physicochemical properties. Their enormous potential makes them particularly attractive to form new and fascinating nanometric drug delivery systems, solving several typical shortcomings encountered in nanomedicine. In this context, the recent developments of dendritic and hyperbranched based systems, together with their application as nanocarriers, have been comprehensively reviewed. This review highlights how the structural complexity can be taken as an evolution parameter of these nanosystems, starting with hyperbranched polymers and evolving to more complex structures such as hybrid dendritic- inorganic nanoparticles and dendronized nano-objects hierarchically designed. Finally, future directions and perspectives in this promising field are briefly discussed.

Nanostructured delivery systems with improved leishmanicidal activity: a critical review.

Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania, which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

Advances in nanomedicine for the treatment of Alzheimer's and Parkinson's diseases.

Alzheimer's disease and Parkinson's disease are the most common neurodegenerative diseases worldwide. Despite all the efforts made by the scientific community, current available treatments have limited effectiveness, without halting the progression of the disease. That is why, new molecules such as growth factors, antioxidants and metal chelators have been raised as new therapeutical approaches. However, these molecules have difficulties to cross the blood-brain barrier limiting its therapeutic effect. The development of nanometric drug delivery systems may permit a targeted and sustained release of old and new treatments offering a novel strategy to treat these neurodegenerative disorders. This review summarized the main investigated drug delivery systems as promising approaches to treat Alzheimer's disease and Parkinson's disease.

Nanomedicine for targeted cancer therapy: Towards the overcoming of drug resistance

Anticancer drug resistance almost invariably emerges and poses major obstacles towards curative therapy of various human malignancies. In the current review we will distinguish between mechanisms of chemoresistance that are predominantly mediated by ATP-driven multidrug resistance (MDR) efflux transporters, typically of the ATP-binding cassette (ABC) superfamily, and those that are independent of such drug efflux pumps. In recent years, multiple nanoparticle (NP)-based therapeutic systems have been developed that were rationally designed to overcome drug resistance by neutralizing, evading or exploiting various drug efflux pumps and other resistance mechanisms. NPs are being exploited for selective drug delivery to tumor cells, to cancer stem/tumor initiating cells and/or to the supportive cancer cell microenvironment, i.e. stroma or tumor vasculature. Some of these NPs are currently undergoing preclinical in vivo studies as well as advanced stages of clinical evaluation with promising results. Nanovehicles harboring a payload of therapeutic drug combinations for the selective targeting and elimination of tumor cells as well as the simultaneous overcoming of mechanisms of drug resistance are a subject of intense research efforts, some of which are expected to enter clinical trials in the near future. In the present review we highlight novel approaches to selectively target cancer cells and overcome drug resistance phenomena, through the use of various nanometric drug delivery systems. In the near future, it is anticipated that innovative theragnostic nanovehicles will be developed which will harbor four major components: (1) a selective targeting moiety, (2) a diagnostic imaging aid for the localization of the malignant tumor and its micro- or macrometastases, (3) a cytotoxic, small molecule drug(s) or novel therapeutic biological(s), and (4) a chemosensitizing agent aimed at neutralizing a resistance mechanism, or exploiting a molecular "Achilles hill" of drug resistant cells. We propose to name these envisioned four element-containing nanovehicle platform, "quadrugnostic" nanomedicine. This targeted strategy holds promise in paving the way for the introduction of highly effective nanoscopic vehicles for cancer therapeutics while overcoming drug resistance.

Atomic force microscopy and photon correlation spectroscopy: Two techniques for rapid characterization of liposomes

The direct evaluation of the heterogeneity of the particle population of nanometric drug delivery systems as liposomes is difficult to achieve owing to the dimension and the carrier characteristics. The influence of the lipidic ratio and composition on the physical stability of liposomes during their storage was investigated using atomic force microscopy (AFM) and photon correlation spectroscopy (PCS). Liposomes were made by a mixture of different lipids and obtained using distinct methods of preparation. AFM images, acquired immediately after the deposition of the sample on mica surface, clearly showed the spherical shape of the lipidic vesicles. In all the 7 months of the experiment, the average sizes of the different liposomes evaluated using the two techniques were comparable. According to PCS analysis, AFM images confirmed that almost all the diversified vesicular systems tended to form aggregates during their storage; this loss of stability was strengthened by the increase of polydispersity index value. The different behaviours observed were to ascribe to the lipidic composition more than the methods of liposome preparation. In conclusion, AFM technique owing to the relative simplicity cold be useful for the technological control of size distribution profile according to the preparative factors and moreover to the batch-to-batch reproducibility.