Gold-capped mesoporous silica nanoparticles as an excellent enzyme-responsive nanocarrier for controlled doxorubicin delivery

Abstract

Mesoporous silica nanoparticles (MSNs) have ideal characteristics as next generation of controlled drug delivery systems. In this study, a MSN-based nanocarrier was fabricated and gold nanoparticle (GNP)-biotin conjugates were successfully grafted onto the pore outlets of the prepared MSN. This bioconjugate served as a capping agent with a peptide-cleavable linker sensitive to matrix metalloproteinases (MMPs), which are overexpressed extracellular proteolytic enzymes in cancerous tissue. The prepared nanocarriers were fully characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infra-red spectroscopy (FTIR), dynamic light scattering (DLS) and thermo gravimetric analysis (TGA). In vitro release studies showed efficient capping of MSNs with gold gate and controlled release of Doxorubicin (DOX) in the presence of matrix metalloproteinase-2 (MMP-2) and acidic pH values. High DOX-loading capacity (21%) and encapsulation efficiency (95.5%) were achieved using fluorescence technique. DOX-loaded nanocarriers showed high cytocompatibility and could efficiently induce cell death and apoptosis in the MMP-2 overexpressed cell lines. Moreover, Haemolysis, platelet activation and inflammatory responses assessment approved excellent hemocompatibility and minimal side effects by encapsulation of DOX in MSNs carrier.     

Intranasal infusion of nanostructured lipid carriers (NLC) containing CNS acting drug and estimation in brain and blood

Abstract

The present study was aimed to evaluate the nanostrucured lipid carriers (NLC) containing duloxetine (DLX-NLC) for intranasal infusion through the nasal cavity of rat. The in vivo nasal infusion studies were performed using Wistar rats and the amount of DLX permeated and its amount in brain and blood was estimated. The effects on absorption rate and type of drug delivery systems (nanocarriers and drug solution) for nose to brain/blood permeation were assessed. DLX was found to be permeated from the nasal cavity into the body of rat and the permeated amount was found to be more in case of DLX-NLC. Approximately 2.5-times better permeation was exhibited by DLX-NLC than DLX-solution. Appreciable amount of DLX was estimated in blood and brain and the estimated amount was higher in case of DLX-NLC. Thus the administration of NLC containing DLX through intranasal route was found to be potential method for the delivery of DLX for the treatment of depression.     

Cleavable PEGylation: a strategy for overcoming the “PEG dilemma” in efficient drug delivery

To prolong the circulation time of drug, PEGylation has been widely used via the enhanced permeability and retention (EPR) effect, thereby providing new hope for better treatment. However, PEGylation also brings the "PEG dilemma", which is difficult for the cellular absorption of drugs and subsequent endosomal escape. As a result, the activity of drugs is inevitably lost after PEG modification. To achieve successful drug delivery for effective treatment, the crucial issue associated with the use of PEG-lipids, that is, “PEG dilemma” must be addressed. In this paper, we introduced the development and application of nanocarriers with cleavable PEGylation, and discussed various strategies for overcoming the PEG dilemma. Compared to the traditional ones, the vehicle systems with different environmental-sensitive PEG-lipids were discussed, which cleavage can be achieved in response to the intracellular as well as the tumor microenvironment. This smart cleavable PEGylation provides us an efficient strategy to overcome “PEG dilemma”, thereby may be a good candidate for the cancer treatment in future.     

Applications of graphene oxide in case of nanomedicines and nanocarriers for biomolecules: review study

In this Review article, recent progress in matter of graphene oxide (GO) synthesis and its functionalization via a vast range of materials, including small molecules, polymers, and biomolecules, were reported and systematically summarized in order to overcome the inherent drawbacks of GO nanocarriers and thereby make these nanocarriers suitable for delivering chemotherapeutic agents, genes, and short interfering RNAs. Briefly, this work describes current strategies for the large scale production of GO and modification of graphene-based nanocarriers surfaces through practical chemical approaches, improving their biocompatibility and declining their toxicity. It also describes the most relevant cases of study suitable to demonstrate the role of graphene and graphene derivatives (GD) as nanocarrier for anti-cancer drugs and genes (e.g. miRNAs). Moreover, the controlled release mechanisms within the cell compartments and blood pH for targeted therapeutics release in the acidic environment of tumor cells or in intracellular compartments are mentioned and explored.     

Recent trends in cancer drug resistance reversal strategies using nanoparticles

Introduction: Resistance to chemotherapy is a major obstacle in the successful amelioration of tumors in many cancer patients. Resistance is either intrinsic or acquired, involving mechanisms such as genetic aberrations, decreased influx and increased efflux of drugs. Strategies for the reversal of resistance involve the alteration of enzymes responsible for drug resistance, the modulation of proteins regulating apoptosis mechanisms and improving the uptake of drugs using nanotechnology. Novel strides in the reversal of drug resistance are emerging, involving the use of nanotechnology, targeting stem cells, etc.

Areas covered: This paper reviews the most recent cancer drug reversal strategies involving nanotechnology for targeting cancer cells and cancer stem cells (CSCs), for enhanced uptake of micro- and macromolecular inhibitors.

Expert opinion: Nanotechnology used in conjunction with existing therapies, such as gene therapy and P-glycoprotein inhibition, has been shown to improve the reversal of drug resistance; the mechanisms involved in this include specific targeting of drugs and nucleotide therapeutics, enhanced cellular uptake of drugs and improved bioavailability of drugs with poor physicochemical characteristics. Important strategies in the reversal of drug resistance include: a multifunctional nanoparticulate system housing a targeting moiety; therapeutics to kill resistant cancer cells and CSCs; cytotoxic drugs and a tumor microenvironment stimuli-responsive element, to release the encapsulated therapeutics.     

Perspectives and potential applications of nanomedicine in breast and prostate cancer

Nanomedicine is a branch of nanotechnology that includes the development of nanostructures and nanoanalytical systems for various medical applications. Among these applications, utilization of nanotechnology in oncology has captivated the attention of many research endeavors in recent years. The rapid development of nano‐oncology raises new possibilities in cancer diagnosis and treatment. It also holds great promise for realization of point‐of‐care, theranostics, and personalized medicine. In this article, we review advances in nano‐oncology, with an emphasis on breast and prostate cancer because these organs are amenable to the translation of nanomedicine from small animals to humans. As new drugs are developed, the incorporation of nanotechnology approaches into medicinal research becomes critical. Diverse aspects of nano‐oncology are discussed, including nanocarriers, targeting strategies, nanodevices, as well as nanomedical diagnostics, therapeutics, and safety. The review concludes by identifying some limitations and future perspectives of nano‐oncology in breast and prostate cancer management. © 2010 Wiley Periodicals, Inc. Med Res Rev     

Sialic acid as a potential approach for the protection and targeting of nanocarriers

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 vitro and 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 vivo and in vitro results 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.     

Biomedical aspects of targeted delivery of drugs to pulmonary endothelium

Drug targeting to selected subcellular compartments of the pulmonary endothelium may optimise treatment of many diseases. This paper describes endothelial determinants that are potentially useful for such targeting, including endothelial ectopeptidases, cell adhesion molecules and novel candidates identified by high-throughput methods, as well as the means to achieve optimal subcellular targeting of drugs in the endothelium that have been explored in cell culture and animal studies. Criteria for determining the applicability for targeting include accessibility, specificity, safety and subcellular precision. The effects of endothelial delivery of therapeutic agents, including the effects mediated by the intervention in the function of the target determinants, must be characterised in the context of given pathological conditions.