Nanomedicine: Nanotechnology, Biology and Medicine

HPV infections: Can they be eradicated using nanotechnology?

Marianna Foldvari — 2011-11-18

Abstract: Human papillomavirus (HPV) infections are considered the most common sexually transmitted diseases, with more than 450 million people worldwide infected. HPVs can cause anogenital warts and neoplasias. One prevalent cancer type caused by HPV (mostly type 16 and 18) is cervical intraepithelial neoplasia (CIN). Nanotechnology tools employed in the development of vaccines and a noninvasive treatment may provide a significant advancement in the global combat against this disease.

Gadolinium metallofullerenol nanoparticles inhibit cancer metastasis through matrix metalloproteinase inhibition: imprisoning instead of poisoning cancer cells

2011-09-19

Abstract: The purpose of this work is to study the antimetastasis activity of gadolinium metallofullerenol nanoparticles (f-NPs) in malignant and invasive human breast cancer models. We demonstrated that f-NPs inhibited the production of matrix metalloproteinase (MMP) enzymes and further interfered with the invasiveness of cancer cells in tissue culture condition. In the tissue invasion animal model, the invasive primary tumor treated with f-NPs showed significantly less metastasis to the ectopic site along with the decreased MMP expression. In the same animal model, we observed the formation of a fibrous cage that may serve as a physical barrier capable of cancer tissue encapsulation that cuts the communication between cancer- and tumor-associated macrophages, which produce MMP enzymes. In another animal model, the blood transfer model, f-NPs potently suppressed the establishment of tumor foci in lung. Based on these data, we conclude that f-NPs have antimetastasis effects and speculate that utilization of f-NPs may provide a new strategy for the treatment of tumor metastasis.From the Clinical Editor: In this study utilizing metallofullerenol nanoparticles, the authors demonstrate antimetastasis effects and speculate that utilization of these nanoparticles may provide a new strategy in metastatic tumor therapy.Graphical Abstract: Gadolinium metallofullerenol nanoparticles inhibit cancer metastasis through matrix metalloproteinase inhibition: imprisoning instead of poisoning cancer cells.

Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging

Suphiya Parveen, Ranjita Misra, Sanjeeb K. Sahoo — 2011-06-09

Abstract: Drug delivery is an interdisciplinary and independent field of research and is gaining the attention of pharmaceutical researchers, medical doctors and industry. A safe and targeted drug delivery could improve the performance of some classic medicines already on the market, and moreover, will have implications for the development and success of new therapeutic strategies such as anticancer drug delivery, peptide and protein delivery and gene therapy. In the last decade, several drug-delivery technologies have emerged and a fascinating part of this field is the development of nanoscale drug delivery devices. Nanoparticles (NPs) have been developed as an important strategy to deliver conventional drugs, recombinant proteins, vaccines and more recently, nucleotides. NPs and other colloidal drug-delivery systems modify the kinetics, body distribution and drug release of an associated drug. This review article focuses on the potential of nanotechnology in medicine and discusses different nanoparticulate drug-delivery systems including polymeric NPs, ceramic NPs, magnetic NPs, polymeric micelles and dendrimers as well as their applications in therapeutics, diagnostics and imaging.From the Clinical Editor: This comprehensive review focuses on different nanoparticulate drug-delivery systems including polymeric NPs, ceramic NPs, magnetic NPs, polymeric micelles and dendrimers as well as their applications in therapeutics, diagnostics and imaging.Graphical Abstract: Multifunctional NPs for therapeutics, diagnostics and imaging

Linear PEI nanoparticles: efficient pDNA/siRNA carriers in vitro and in vivo

2011-06-16

Abstract: Linear polyethylenimine (lPEI, 25 kDa) nanoparticles' (LPN) series was synthesized by varying percentage of cross-linking with 1,4-butanediol diglycidyl ether (BDE) and their size, surface charge, morphology, pDNA protection/release, cytotoxicity and transfection efficiency were evaluated. Synthesized nanoparticles (NPs) were spherical in shape (size: ∼109 – 235 nm; zeta potential: +38 to +16 mV). These NPs showed increased buffering capacity with increasing percent cross-linking and also exhibited excellent transfection efficiency (i.e., ∼1.3 – 14.7 folds in case of LPN-5) in comparison with lPEI and the commercial transfection agents used in this study. LPN-5 based GFP-specific siRNA delivery resulted in ∼86% suppression of targeted gene expression. These particles were relatively nontoxic in vitro (in cell lines) and in vivo (in Drosophila). In vivo gene expression studies using LPN-5 in Balb/c mice through intravenous injection showed maximum expression of the reporter gene in the spleen. These results together demonstrate the potential of these particles as efficient transfection reagents.From the Clinical Editor: The authors demonstrate a novel method of synthesizing linear PEI nanoparticles to utilize these as transfection agents.Graphical Abstract: A series of lPEI nanoparticles (LPNs) has been synthesized keeping intact the overall amines and cell viability characteristics of lPEI using BDE as a crosslinker. These LPNs exhibited significantly improved transfection efficiency with relatively negligible cytotoxicity compared to bPEI, lPEI and other commercially available transfection reagents both in vitro and in vivo.

Liposome-induced complement activation and related cardiopulmonary distress in pigs: factors promoting reactogenicity of Doxil and AmBisome

2011-06-27

Abstract: Hypersensitivity reactions to liposomal drugs, often observed with Doxil and AmBisome, can arise from activation of the complement (C) system by phospholipid bilayers. To understand the mechanism of this adverse immune reaction called C activation-related pseudoallergy (CARPA), we analyzed the relationship among liposome features, C activation in human serum in vitro, and liposome-induced cardiovascular distress in pigs, a model for human CARPA. Among the structural variables (surface charge, presence of saturated, unsaturated, and PEGylated phospholipids, and cisplatin vs. doxorubicin inside liposomes), high negative surface charge and the presence of doxorubicin were significant contributors to reactogenicity both in vitro and in vivo. Morphological analysis suggested that the effect of doxorubicin might be indirect, via distorting the sphericity of liposomes and, if leaked, causing aggregation. The parallelism among C activation, cardiopulmonary reactions in pigs, and high rate of hypersensitivity reactions to Doxil and AmBisome in humans strengthens the utility of the applied tests in predicting the risk of CARPA.From the Clinical Editor: The authors studied complement activation-related pseudoallergy (CARPA) in a porcine model and demonstrate that high negative surface charge and drug effects leading to distortion of liposome sphericity might be the most critical factors leading to CARPA. The applied tests might be used to predict CARPA in humans.Graphical Abstract: Blood pressure changes in pigs following bolus administration of AmBisome.

Novel nanostructured lipid-dextran sulfate hybrid carriers overcome tumor multidrug resistance of mitoxantrone hydrochloride

2011-06-27

Abstract: Novel nanostructured lipid-dextran sulfate hybrid carriers (NLDCs) were successfully developed for sustained delivery of water-soluble cationic mitoxantrone hydrochloride (MTO) and overcoming multidrug resistance. The introduction of negative polymer of dextran sulfate sodium significantly improved the encapsulation efficiency (97.4%) and sustained the release of MTO (86.9% at 72 hours). In vivo pharmacokinetics in rats after intravenous administration demonstrated that MTO-loaded NLDCs (MTO-NLDCs) had higher area under the curve and longer half-life than MTO solution (MTO-Sol). In the biodistribution study, NLDCs significantly improved the MTO levels in plasma, spleen, and brain, and decreased the distribution of MTO in heart and kidney. In comparison with MTO-Sol, MTO-NLDCs efficiently enhanced cytotoxicity through the higher accumulation of MTO in breast cancer resistance protein (BCRP)-overexpressing MCF-7/MX cells. MTO-NLDCs entered into the resistant cancer cells by the clathrin-mediated endocytosis pathway, which escaped the efflux induced by BCRP transporter and thereby overcame the multidrug resistance of MCF-7/MX cells.From the Clinical Editor: In this study, novel nanostructured lipid-dextran sulfate hybrid carriers were synthesized and utilized for sustained delivery of mitoxantrone hydrochloride. The utilized methods successfully addressed multidrug resistance to this chemotherapy agent.Graphical Abstract: Novel nanostructured lipid‑dextran sulfate hybrid carriers (NLDCs) were successfully developed with improved encapsulation efficiency, sustained-release characteristics, desired pharmacokinetics and biodistribution, enhanced cellular uptake and cytotoxicity, and reversing effect on multidrug resistance for water-soluble cationic mitoxantrone hydrochloride.

A novel dextran-oleate-cRGDfK conjugate for self-assembly of nanodrug

Zhe Wang, Ting Yee Lee, Paul C. Ho — 2011-06-27

Abstract: We report a novel synthetic biocompatible material: a conjugate with a fatty acid-substituted dextran decorated with cRGDfK peptide, which was used as a stable coating material instead of the conventional poly(ethylene glycol) for nanodrug preparation. This novel dextran-oleate-cRGDfK conjugate (DO-cRGDfk) could self-assemble into a micellar structure in aqueous solution, and was used as a surfactant to formulate nanodrug with poly(d,l-lactic-co-glycolic) acid as matrix to encapsulate paclitaxel with high drug-loading efficiency. The conjugate allowed the fabrication of nanodrug with a targeting moiety on its surface in a simple and robust step. The resultant nanoparticles could induce cellular apoptosis more effectively than that of the commercial paclitaxel formulation, Taxol. Thus, DO-cRGDfk could be used as an alternative to poly(ethylene glycol) as a biocompatible surface coating polymeric material for nanoparticle preparation.From the Clinical Editor: The authors describe a novel synthetic biocompatible conjugate, which consists of a fatty acid-substituted dextran decorated with cRGDfK peptide. This conjugate was used as a stable coating material for nanodrug preparation, and can be used in place of conventional PEG.Graphical Abstract: A novel biocompatible and biodegradable material - a conjugate with a fatty acid substituted dextran decorated with cRGDfK peptide which can be used as a surfactant to prepare integrin targeting nanodrug in a single step with PLGA as the matrix and without the need for further particle surface modification for targeting. This new conjugate could be regarded as an alternative to PEG as a surface coating material for the preparation of nanoparticle.

Gold-doxorubicin nanoconjugates for overcoming multidrug resistance

Yan-Juan Gu, Jinping Cheng, Cornelia Wing-Yin Man, Wing-Tak Wong, Shuk Han Cheng — 2011-06-27

Abstract: Multidrug resistance (MDR) is a major clinical obstacle to the success of cancer chemotherapy. Here we developed a gold-doxorubicin (DOX) nanoconjugates system to overcome MDR. Gold nanoparticles (AuNPs) were first PEGylated as Au-PEG-NH2, and DOX was then grafted onto AuNPs via a cleavable disulfide linkage (Au-PEG-SS-DOX). Confocal images revealed that the extent of intracellular uptake of Au-PEG-SS-DOX was greater than that of free DOX in the MDR cells, and inductively coupled plasma mass spectroscopy analysis further confirmed that AuNPs significantly increased the level of drug accumulation in MDR cells at a nanoparticles dose greater than 15 μM. The cytotoxicity study demonstrated that the Au-PEG-SS-DOX nanoconjugates system efficiently released the anticancer drug DOX and enhanced its cytotoxicity against MDR cancer cells. This study highlights the potential of using AuNPs for overcoming of MDR in cancer chemotherapy.From the Clinical Editor: This study demonstrates that gold nanoparticles can be successfully applied to overcome MDR in cancer chemotherapy.Graphical Abstract: Gold-doxorubicin nanoconjugates were developed by grafting doxorubicin (DOX) onto polyethylene glycol (PEG)-modified gold (Au) nanoparticles (Au-NPs) via cleavable disulfide (SS) linkage. The Au-PEG-SS-DOX nanoconjugates exhibited higher intracellular uptake and greatly enhanced cytotoxicity for multidrug-resistant cells HepG2-R compared to free DOX. This study highlights the potential of using Au-NPs for overcoming multidrug resistance in cancer chemotherapy.

In vivo tumor suppression efficacy of mesoporous silica nanoparticles-based drug-delivery system: enhanced efficacy by folate modification

Jie Lu, Zongxi Li, Jeffrey I. Zink, Fuyuhiko Tamanoi — 2011-06-16

Abstract: Mesoporous silica nanoparticles (MSNs) have proven to be promising vehicles for drug delivery. However, despite the potential, few studies have extended the success of in vitro studies to animal settings. In this article, we report the efficacy of MSNs using two different human pancreatic cancer xenografts on different mouse species. Significant tumor-suppression effects were achieved with camptothecin-loaded MSNs. Dramatic improvement of the potency of tumor suppression was obtained by surface modifying MSNs with folic acid. Dose-dependent tumor suppression was observed, establishing 0.5 mg of CPT-loaded MSNs per mouse as a minimum dose sufficient for achieving complete tumor growth inhibition. Renal excretion of MSNs was also confirmed with transmission electron microscopy (TEM) imaging. These findings highlight attractive features (biocompatibility, renal clearance and high efficacy for delivering anticancer drugs) of MSNs as a drug-delivery system.From the Clinical Editor: In this study, mesoporous silica nanoparticles are used as chemotherapy delivering agents in two different human pancreatic cancer xenografts and different mouse species. Significant tumor-suppression effects, biocompatibility and efficient renal clearance are demonstrated.Graphical Abstract: Significant tumor-suppression effects were achieved with camptothecin-loaded mesoporous silica nanoparticles (MSNs). Dramatic improvement of the potency of tumor suppression was obtained by surface modifying MSNs with folic acid. These findings highlight attractive features (biocompatibility, renal clearance and tumor-suppressing ability) of MSNs as a drug-delivery system.

Simultaneous basal-bolus delivery of fast-acting insulin and its significance in diabetes management

Guangjiong Qin, Yunhua Gao, Yan Wu, Suohui Zhang, Yuqin Qiu, Fang Li, Bai Xu — 2011-06-16

Abstract: Insulin delivery relies on subcutaneous or intravascular injection, leading to reduced patient compliance. Transdermal delivery of insulin has been successfully demonstrated but dose accuracy and skin irritation are problematic in addition to the complex basal-bolus delivery profile required by insulin therapy. Here we present a novel intraepidermal delivery technology (delivered site at epidermis layer, <150 μm) by combining skin pretreatment with short microneedles (<150 μm in length) and iontophoresis transdermal patch (enhanced transport via electrical field) that can provide a continuous basal dose and on-demand bolus dosing for mealtime insulin needs. To our knowledge, this is the first demonstration of therapeutic equivalence between fast-acting human regular insulin and long-acting insulin with possibilities for on-demand dose adjustment. This new intraepidermal delivery technology is likely to change the therapy regimen of patients suffering from insulin-dependent diabetes mellitus and provide a way to lower cost in comparison with insulin pumps and improve patient compliance.From the Clinical Editor: The authors present a novel intraepidermal insulin delivery technology by combining skin pretreatment with short microneedles and iontophoresis transdermal patch to provide a continuous basal dose and on-demand bolus dosing. This new method is has the potentials to replace insulin pumps by offering a cost effective alternative with less inconvenience and improved compliance.Graphical Abstract: The technology of combining microneedle intraepidermal delivery (IED) and iontophoresis (IP) can provide a continuous basal dose and on-demand bolus dose for meal time coverage using rapid-acting regular human insulin.

In vivo cancer imaging by poly(ethylene glycol)-b-poly(ɛ-caprolactone) micelles containing a near-infrared probe

Hyunah Cho, Guilherme L. Indig, Jamey Weichert, Ho-Chul Shin, Glen S. Kwon — 2011-06-27

Abstract: Noninvasive near-infrared (NIR) fluorescence imaging is a promising technique for the intraoperative assessment of solid tumor removal. We incorporated a lipophilic NIR probe, 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide (DiR), in poly(ethylene glycol)-b-poly(ɛ-caprolactone) (PEG-b-PCL) micelles, resulting in DiR solubilization in water, occupying nanoscopic PEG-b-PCL micelles. DiR in a self-quenched or nonquenched state showed different kinetics of release from PEG-b-PCL micelles in vitro; however, both obtained high tumor delineation (tumor-to-muscle ratio of 30–43 from collected organs). These results suggest that PEG-b-PCL micelles with DiR are a promising nanosized imaging agent that will provide a basis for enhanced surgical guidance via NIR visualization of tumors.From the Clinical Editor: In this paper, noninvasive near-infrared fluorescence imaging coupled with specific lipophilic probes is discussed as a promising technique for intraoperative assessment of solid tumor removal, leading to optimized outcomes for in toto removal of tumors.Graphical Abstract: PEG-b-PCL micelles migrated into solid tumors with incorporated DiR in either a non-quenched state (left) or a self-quenched state (right) by the EPR effect, delineating solid tumors. Non-quenched DiR displayed a rapid onset of strong fluorescence intensity at solid tumors. On the other hand, self-quenched DiR displayed relatively lower fluorescence intensity, but a gradual increase over time at solid tumors.

Formulation and optimization of nanotransfersomes using experimental design technique for accentuated transdermal delivery of valsartan

2011-06-27

Abstract: The purpose of this work was to develop and statistically optimize nanotransfersomes for enhanced transdermal of valsartan vis-à-vis traditional liposomes. Nanotransfersomes bearing valsartan were prepared by conventional rotary evaporation method and characterized for various parameters including entrapment efficiency, vesicles shape, size, size distribution, and skin permeation. In vivo antihypertensive activity conducted on Wistar rats was also taken as a measure of performance of nanotransfersomes and liposomes. Nanotransfersomes proved significantly superior in terms of amount of drug permeated in the skin, with an enhancement ratio of 33.97 ± 1.25 when compared to rigid liposomes. This was further confirmed through a confocal laser scanning microscopy study. Nanotransfersomes showed better antihypertensive activity in comparison to liposomes by virtue of better permeation through Wistar rat skin. Finally, it could be concluded that the nanotransfersomes accentuates the transdermal flux of valsartan and could be used as a carrier for effective transdermal delivery of valsartan.From the Clinical Editor: In this paper, the authors discuss the development and optimization of nanotransfersomes for enhanced transdermal of valsartan and demonstrate accentuated transdermal compared to standard preparations.Graphical Abstract: Valsartan-bearing nanotransfersomes were successfully prepared by conventional rotary evaporation sonication method. Nanotransfersomes were characterized for various parameters including entrapment efficiency, vesicles shape, size, size distribution, and skin permeation. Flexible nanotransfersomes provided better flux and higher entrapment efficiency, and proved significantly superior in terms of amount of drug permeated in the skin, when compared to rigid liposomes. Because Transfersomes are composed of surfactant and have better rheology and hydration properties, they have superior skin penetration ability over traditional liposomes, which are confined to the skin surface.

Chitosan enhances the stability and targeting of immuno-nanovehicles to cerebro-vascular deposits of Alzheimer's disease amyloid protein

2011-06-27

Abstract: Alzheimer's disease amyloid β (Aβ) proteins accumulate in the cerebral vasculature and cause cerebral amyloid angiopathy (CAA). The objective of this study was to resolve critical formulation issues in developing nanoparticles (NPs) capable of permeating the blood brain barrier (BBB) and targeting cerebrovascular Aβ proteins. To achieve this objective we designed immuno-nanovehicles, which are chitosan-coated poly lactic-co-glycolic acid (PLGA) NPs conjugated with a novel anti-Aβ antibody. Measurements made according to Derjaguin-Landau-Verwey-Overbeek (DLVO) theory indicated that the immuno-nanovehicles have a much lower propensity to aggregate than the control nanovehicles. Immuno-nanovehicles showed enhanced uptake at the BBB and better targeting of the Aβ proteins deposited in the CAA model in vitro in comparison with the control nanovehicles. In addition, chitosan enhanced aqueous dispersibility and increased the stability of immuno-nanovehicles during lyophilization, thus transforming them into ideal vehicles for delivering therapeutic and diagnostic agents to the cerebral vasculature ridden with vascular amyloid.From the Clinical Editor: In this study, the authors report the development of chitosan-coated PLGA nanoparticles conjugated with anti-amyloid antibody to be used as immuno-nanovehicles to image cerebral amyloid angiopathy deposits in vivo. This method enables delivering therapeutic and diagnostic agents to the cerebral vasculature ridden with vascular amyloid.Graphical Abstract: Alzheimer's disease amyloid proteins accumulate in the cerebral vasculature to cause cerebral amyloid angiopathy (CAA). Immuno-nanovehicle successfully targeted the cerebrovascular amyloid deposits in a cellular CAA model.

Cover

2012-02-01

About the Cover

2012-02-01

Editorial Board

2012-02-01

Nanomedicine: Nanotechnology, Biology and Medicine

HPV infections: Can they be eradicated using nanotechnology?

Gadolinium metallofullerenol nanoparticles inhibit cancer metastasis through matrix metalloproteinase inhibition: imprisoning instead of poisoning cancer cells

Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging

Linear PEI nanoparticles: efficient pDNA/siRNA carriers in vitro and in vivo

Liposome-induced complement activation and related cardiopulmonary distress in pigs: factors promoting reactogenicity of Doxil and AmBisome

Novel nanostructured lipid-dextran sulfate hybrid carriers overcome tumor multidrug resistance of mitoxantrone hydrochloride

A novel dextran-oleate-cRGDfK conjugate for self-assembly of nanodrug

Gold-doxorubicin nanoconjugates for overcoming multidrug resistance

In vivo tumor suppression efficacy of mesoporous silica nanoparticles-based drug-delivery system: enhanced efficacy by folate modification

Simultaneous basal-bolus delivery of fast-acting insulin and its significance in diabetes management

In vivo cancer imaging by poly(ethylene glycol)-b-poly(ɛ-caprolactone) micelles containing a near-infrared probe

Formulation and optimization of nanotransfersomes using experimental design technique for accentuated transdermal delivery of valsartan

Chitosan enhances the stability and targeting of immuno-nanovehicles to cerebro-vascular deposits of Alzheimer's disease amyloid protein

Cover

About the Cover

Editorial Board

Table of Contents