Dextran Nanoparticles Research Articles

Injectable Nano-Network for Glucose-Mediated Insulin Delivery

Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial “closed-loop” system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered w...

Development of dextran nanoparticles for stabilizing delicate proteins

One of the most challenging problems in the development of protein pharmaceuticals is to deal with stabilities of proteins due to its complicated structures. This study aims to develop a novel approach to stabilize and encapsulate proteins into dextran nanoparticles without contacting the interface between the aqueous phase and the organic phase. The bovine serum albumin, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), β-galactosidase, and myoglobin were selected as model proteins. The proteins were added into an aqueous solution containing the dextran and polyethylene glycol, and then encapsulated into dextran nanoparticles by aqueous-aqueous freezing-induced phase separation. The encapsulation efficiency and recovery of dextran nanoparticles were determined. The dextran nanoparticles loaded with proteins were characterized by scanning electron microscopy and particle size analysis. The protein aggregation was determined by size-exclusion chromatography-high-performance chromatography, and the bioactivity of proteins recovered during formulation steps was determined. The bioactivity of GM-CSF, G-CSF, and β-galactosidase were examined by the proliferation of TF-1 cell, NSF-60 cell, and ortho-nitrophenyl-β-galactoside assay, respectively. The results of bioactivity recovered show that this novel dextran nanoparticle can preserve the protein's bioactivity during the preparation process. LysoSensor™ Yellow/Blue dextran, a pH-sensitive indicator with fluorescence excited at two channels, was encapsulated into dextran nanoparticles to investigate the ability of dextran nanoparticles to resist the acidic microenvironment (pH < 2.5). The result shows that the dextran nanoparticles attenuate the acidic microenvironment in the poly (lactic-co-glycolic acid) microsphere by means of the dilution effect. These novel dextran nanoparticles provided an appealing approach to stabilize the delicate proteins for administration.

Studies on the structure of coumarin-modified dextran nanoparticles by fluorescence spectroscopy

The photophysical and photochemical characteristics of nano-scaled particles obtained via solvent displacement from coumarin-modified dextrans were studied by means of absorption- and fluorescence-spectroscopy. The environment-dependent fluorescence emission of the pendant 4-methyl-7-alkoxy coumarin groups was exploited as a probe to gain information about the inner structure of the polysaccharide based nanoparticles. Time-resolved fluorescence measurements showed that the particles had two domains of different polarity and it could be confirmed that the core of the nano-assemblies contained water. Moreover, preliminary experiments were carried out demonstrating the possibility to control the morphology of the nanoparticles by the light induced 2π+2π cycloaddition of the coumarin substituents.

In This Issue

HomeCirculation ResearchVol. 112, No. 5In This Issue Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBIn This Issue Originally published1 Mar 2013https://doi.org/10.1161/RES.0b013e31828c5b1dCirculation Research. 2013;112:743Macrophage Targeted PET/MRI (p 755)Download figureDownload PowerPointMajmudar et al devise a macrophage imaging technique that could help identify unstable atherosclerotic plaques.Macrophage abundance in atherosclerotic plaques is strongly associated with the risk of plaque rupture, which can cause thrombus formation and even myocardial infarction or stroke. Therefore, it is important to image and quantify macrophages in human plaques to identify high-risk patients and to inform therapeutic interventions. However, existing imaging techniques lack sufficient sensitivity. Therefore, Majmudar and colleagues set out to develop a viable alternative. They generated radioactive dextran nanoparticles that could be efficiently taken up by macrophages. They injected these nanoparticles into the tail veins of mice and, after allowing time for phagocytosis, they tracked their vascular distribution using a combination of positron emission tomography (PET)—to detect the radioactive signal—and MRI—to determine anatomical location. They found that compared with wild-type mice, mice that were prone to atherosclerosis exhibited considerably higher nanoparticle PET signals from their aortas. The team also found that preventing the recruitment of macrophages to inflammation sites lowered these aortic PET signals. Because nanoparticles used in the study were biodegradable, this technique could perhaps be used to monitor atherosclerotic plaques in humans, say the authors.Cathelicidins and Monocyte Adhesion (p 792)Download figureDownload PowerPointWantha et al show how neutrophils recruit monocytes to sites of inflammation.It is currently believed that during early stages of acute inflammation, soluble granule proteins released from neutrophils are required for subsequent recruitment of monocytes to the inflammation site. However, the underlying mechanisms remain unclear. Wantha and colleagues investigated the monocyte-attracting ability of cathelicidin and cathepsin - two neutrophil granule proteins conserved between mice and humans. They found that deletion of cathelicidin in mice reduced the recruitment of classical monocytes to inflammation sites. Mice lacking cathepsin, on the other hand, showed no such defect. In vitro experiments using cathelicidin treated human vascular endothelial cells confirmed that the protein is indeed able to recruit classical monocytes. By blocking different receptor proteins on the surface of monocytes, the team discovered that one specific receptor was responsible for mediating cathelicidin-dependent recruitment. Interaction between cathelicidin and this receptor, FRP2, induced the activation of integrins that enable monocytes to adhere to sites of inflammation. This interaction could thus be targeted to treat for a variety of inflammatory disorders, say the authors.SDF-1 in Heart Failure (p 816)Download figureDownload PowerPointPenn et al report the outcome of a Phase I gene therapy trial for the treatment of ischemic heart failure.The tissue damage that occurs after a myocardial infarction can lead to progressive heart failure and, if left untreated, to death. Mending damaged cardiac tissue with the help of stem cells is the goal of several current therapeutic investigations. One such approach, adopted by Penn and colleagues, is to recruit the body’s own stem cells to the heart. Stromal cell-derived factor 1 (SDF-1) is a naturally occurring cytokine that attracts stem cells and is upregulated in injured tissues. In the infarcted heart tissue, however, SDF-1 action lasts less than a week, after which stem cell recruitment diminishes. Artificially maintaining SDF-1 expression in damaged myocardium has been shown to improve cardiac function in a number of pre-clinical studies. Penn et al now provide preliminary evidence that the same approach works in patients too. They injected a non-viral DNA vector encoding the SDF-1 gene into the peri-infarcted myocardia of 17 heart failure patients. Four months later, these patients exhibited improvements in quality of life, 6 minute walking distance, and in the overall clinical classification of their condition. And 12 months later, these improvements persisted. Although this was a relatively small Phase I trial, the results indicate that a larger, randomized trial is warranted. Previous Back to top Next FiguresReferencesRelatedDetails March 1, 2013Vol 112, Issue 5 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/RES.0b013e31828c5b1d Originally publishedMarch 1, 2013 PDF download Advertisement

The activity against Ehrlich's ascites tumors of doxorubicin contained in self assembled, cell receptor targeted nanoparticle with simultaneous oral delivery of the green tea polyphenol epigallocatechin-3-gallate

Doxorubicin (DOX) is a well-known anticancer drug used for the treatment of a wide variety of cancers. However, undesired toxicity of DOX limits its uses. To address the issue of minimizing toxicity of DOX by making it targeted towards cancer cells, DOX was entrapped in self-assembled 6-O-(3-hexadecyloxy-2-hydroxypropyl)-hyaluronic acid (HDHA) nanoparticles. We hypothesized that by encapsulating the drug in biodegradable nanoparticles, its therapeutic efficacy would improve, if targeted against cancer cells. We synthesized cell receptor targeted, DOX loaded HDHA nanoparticles (NPs) and non-targeted DOX loaded O-hexadecylated dextran (HDD) nanoparticles (NPs) and characterized them for their entrapment efficiency, percent yield, drug load, surface morphology, particle size and in vitro drug release. The anticancer efficacy of DOX loaded HDHA-NPs was evaluated by measuring the changes in tumor volumes, tumor weights, and mean survival rate of Swiss albino mice grafted with Ehrlich's ascites carcinoma (EAC) cells. For this, the animals were given HDHA-DOX-NPs (1.5 mg/kg b.wt.) intravenously and a green tea polyphenol, Epigallocatechin-3-gallate (EGCG) (20 mg/kg b.wt.), orally through gavage. The targeted NP dose with EGCG significantly increased mean survival time of the animals and enhanced the therapeutic efficacy of the drug compared to the non-targeted NPs and free DOX. Further, we showed that these NPs (HDD and HDHA) were more active in the presence of EGCG than DOX alone in inducing apoptosis in EAC cells as evident by an increase in sub-G1 cells (percent), Annexin V positive cells and chromatin condensation along with the reduction in mitochondrial membrane potential (MMP). The study demonstrates that DOX loaded HDHA-NPs along with EGCG significantly inhibit the growth of EAC cells with ∼38-fold dose advantage compared to DOX alone and thus opens a new dimension in cancer chemotherapy.

Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques

Myeloid cell content in atherosclerotic plaques associates with rupture and thrombosis. Thus, imaging of lesional monocytes and macrophages could serve as a biomarker of disease progression and therapeutic intervention. To noninvasively assess plaque inflammation with dextran nanoparticle (DNP)-facilitated hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Using clinically approved building blocks, we systematically developed 13-nm polymeric nanoparticles consisting of cross-linked short chain dextrans, which were modified with desferoxamine for zirconium-89 radiolabeling ((89)Zr-DNP) and a near-infrared fluorochrome (VT680) for microscopic and cellular validation. Flow cytometry of cells isolated from excised aortas showed DNP uptake predominantly in monocytes and macrophages (76.7%) and lower signal originating from other leukocytes, such as neutrophils and lymphocytes (11.8% and 0.7%, P<0.05 versus monocytes and macrophages). DNP colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET/MRI revealed high uptake of (89)Zr-DNP in the aortic root of apolipoprotein E knock out (ApoE(-/-)) mice (standard uptake value, ApoE(-/-) mice versus wild-type controls, 1.9±0.28 versus 1.3±0.03; P<0.05), corroborated by ex vivo scintillation counting and autoradiography. Therapeutic silencing of the monocyte-recruiting receptor C-C chemokine receptor type 2 with short-interfering RNA decreased (89)Zr-DNP plaque signal (P<0.05) and inflammatory gene expression (P<0.05). Hybrid PET/MRI with a 13-nm DNP enables noninvasive assessment of inflammation in experimental atherosclerotic plaques and reports on therapeutic efficacy of anti-inflammatory therapy.

Effect of Coating Materials on Lymph Nodes Detection Using Magnetite Nanoparticles

Magnetite nanoparticles-based contrast agents used in magnetic resonance imaging has offered new promise for early detection of lymph nodes and their metastases. Beside the value of Magnetite core of superparamagnetic nanoparticles as an efficient contrast agent, the type of coating material is important for their biodistribution properties. In this study, various coating materials were synthesized and their detection sensitivities were evaluated in axillary lymph nodes. These nanoparticles were prepared in an aqueous-phase under ultrasonic irradiation. Four different types of coatings including polyethylene glycol, Dextran, Carboxymethyl Dextran, and double layer of PEG-Dextran were used as the capping agents. The crystal structure, morphology, hydrodynamic size and magnetic properties of the nanoparticles were characterized. In-vitro relaxivity measurements along with post contrast in-vivo studies on rat demonstrated that the synthesized nanoparticles are applicable as magnetic resonance imaging contrast agents for imaging of the lymph nodes. In-vitro magnetic resonance imaging showed the optimum r2/r1 for Dextran nanoparticles. The best contrast to noise ratio (CNR) for in-vivo studies was obtained by the Dextran-coated nanoparticles.

Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes.

Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH(2)Cl(2) (organic):PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery.

Functionalizing Biodegradable Dextran Scaffolds Using Living Radical Polymerization: New Versatile Nanoparticles for the Delivery of Therapeutic Molecules

Conferring biodegradability to nanoparticles is vitally important when nanomedicine applications are being targeted, as this prevents potential problems with bioaccumulation of byproducts after delivery. In this work, dextran has been modified (and rendered hydrophobic) by partial acetalation. A solid state NMR method was first developed to fully characterize the acetalated polymers. In a subsequent synthetic step, RAFT functionality was attached via residual unmodified hydroxyl groups. The RAFT groups were then used in a living free radical polymerization reaction to control the growth of hydrophilic PEG-methacrylate chains, thereby generating amphiphilic comblike polymers. The amphiphilic polymers were then self-assembled in water to form various morphologies, including small vesicles, wormlike rods, and micellar structures, with PEG at the periphery acting as a nonfouling biocompatible polymer layer. The acetalated dextran nanoparticles were designed for potential doxorubicin (DOX) delivery application based on the premise that in the cell compartments (endosome, lysozome) the acetalated dextran would hydrolyze, destroying the nanoparticle structure, releasing the encapsulated DOX. In-vitro studies confirmed minimal cytotoxicity of the (unloaded) nanoparticles, even after 3 days, proving that the hydrolysis products from the acetal groups (methanol and acetone) had no observable cytotoxic effect. An intriguing initial result is reported that in vitro studies of DOX-loaded dextran-nanoparticles (compared to free DOX) revealed an increased differential toxicity toward a cancer cell line when compared to a normal cell line. Efficient accumulation of DOX in a human neuroblastoma cell line (SY-5Y) was confirmed by both confocal microscopy and flow cytometry measurements. Furthermore, the time dependent release of DOX was monitored using fluorescence lifetime imaging microscopy (FLIM) in SY-5Y live cells. FLIM revealed bimodal lifetime distributions, showing the accumulation of both DOX-loaded dextran-nanoparticles and subsequent release of DOX in the living cells. From FLIM data analysis, the amount of DOX released in SY-5Y cells was found to increase from 35% to 55% when the incubation time increased from 3 h to 24 h.

Characterization of Chitosan-Carboxymethyl Dextran Nanoparticles as a Drug Carrier and as a Stimulator of Mouse Splenocytes

The in vitro drug-release behavior of chitosan-carboxymethyl dextran nanoparticles (CDNP) containing cefmetazole, 5-fluorouracil (5-FU) or indocyanine green (ICG), and the in vitro effect of CDNP on mouse B16 melanoma cell proliferation and in vivo modulation effect of CDNP on serum cytokines and spleen lymphocytes in mice were evaluated in this study. Drug-loaded CDNP were prepared by embedding (for cefmetazole or 5-FU) and absorption (for ICG), and the particle size was increased with increased drug association efficiency (AE) and decreased surface amino group content. Prolonged release of cefmetazole (540 min) or 5-FU (360 min) from CDNP was observed when compared to that of nanoparticle-free cefmetazole (210 min) or 5-FU (50 min), and the release of cefmetazole or 5-FU from CDNP98 (CDNP made with 98% degree of deacetylation (DD) chitosan) was slower than from CDNP78 (CDNP made with 78% DD chitosan). High AE (72.0-98.6%), undetectable surface amino group content and dramatically increased particle size (1076.9-1506.0 nm) of ICG-loaded CDNP with undetectable release of ICG within 48 h revealed the good affinity between ICG and CDNP. Twenty-five to 100 μg/ml of CDNP elicited dose-dependent inhibitory effects on B16 tumor cell proliferation, and CDNP98 was more effective than CDNP78. CDNP78 regulated serum IL-17 level in up-regulating IL-4, IL-6, IL-10, IL-23 and TGF-β within 3 h; on the other hand, CDNP98 significantly down-regulated TGF-β and had no induction effect on IL-23 within 24 h. In addition, reduced IL-17 was observed in CDNP at 24 h. CDNP98 was more effective than CDNP78 in stimulating mouse splenic T CD4+, TCD8+ and NK cell proliferation within 24 h, while CDNP78 was superior to CDNP98 in stimulating B CD19+ cells. The ability of CDNP to be the drug carrier and to enhance both humoral and cell-mediated immune response in this study demonstrated its promising potential to be applied as biomedical material.

Fabrication and characterization of a new MRI contrast agent based on a magnetic dextran–spermine nanoparticle system

This study aims to fabricate and formulate a new magnetic resonance imaging (MRI) contrast agent based on a dextran–spermine nanoparticulate system loaded with super paramagnetic iron oxide nanoparticles (SPION). SPION-loaded spermine–dextran nanoparticles were prepared according to a procedure based on the ionic gelation of dextran–spermine with sodium tripolyphosphate (TPP) anions. The effects of process parameters such as pH, concentration of spermine dextran, TPP to dextran–spermine and SPION to dextran–spermine weight ratios, and TPP addition rate were fully investigated to find the optimized formulation through the response surface methodology. At the optimum condition, 75% of the magnetic iron oxide nanoparticles added to the polymeric solution were entrapped in dextran–spermine nanoparticles. Samples were investigated by transmission electron microscopy. The mean particle size of the nanoparticles determined by particle size analyzer was found to be 65 nm at the optimum condition with zeta potential of +90 mV. The SPION-loaded dextran–spermine nanoparticle formulation has the same superparamagnetic properties as SPIONs and at same iron concentration the saturation magnetization (Ms) of the SPION-loaded dextran–spermine nanoparticles was larger than SPIONs. In vitro MRI was performed with gradient echo and spin-echo sequences at 1.5 T. By increasing of iron concentration, the T 2 relaxation times were reduced. Thus, indicating that the saturation magnetization and r 2 and $$ r_{2}^{*} $$ relaxivities were enhanced, and the contrast effects were improved in comparison to commercial SPIONs.

Preparation and characterization of recombinant human growth hormone–Zn2+-dextran nanoparticles using aqueous phase–aqueous phase emulsion

An effective and simple method was developed to prepare spherical and uniform-sized recombinant human growth hormone (rhGH)–Zn2+-dextran nanoparticles (NPs) for a variety of delivery applications of the delicate protein. The results showed that the prepared rhGH-Zn2+-dextran particles were spherical, glassy, and uniform in size. rhGH recovered from the NPs maintained its structural integrity and its bioactivity well, as suggested by the Nb2-11 cell proliferation assay. Using polyethylene glycol and polysaccharide to mediate Zn2+-induced precipitation has proved to be a promising method to prepare spherical protein-loaded NPs with desired sizes and preserved protein stability. From the Clinical EditorThis basic science paper discusses a simple yet effective method to prepare spherical and uniform-sized recombinant human growth hormone (rhGH)-Zn2+-dextran nanoparticles for a variety of delivery applications.

Controlled-release and preserved bioactivity of proteins from (self-assembled) core-shell double-walled microspheres

In order to address preserved protein bioactivities and protein sustained-release problems, a method for preparing double-walled microspheres with a core (protein-loaded nanoparticles with a polymer-suspended granule system-formed core) and a second shell (a polymer-formed shell) for controlled drug release and preserved protein bioactivities has been developed using (solid-in-oil phase-in-hydrophilic oil-in-water (S/O/Oh/W)) phases. The method, based on our previous microsphere preparation method (solid-in-oil phase-in-hydrophilic oil-in-water (S/O/Oh/W), employs different concentric poly(D,L-lactide-co-glycolide), poly(D,L-lactide), and protein-loaded nanoparticles to produce a suspended liquid which then self-assembles to form shell-core microspheres in the hydrophilic oil phase, which are then solidified in the water phase. Variations in the preparation parameters allowed complete encapsulation by the shell phase, including the efficient formation of a poly(D,L-lactide) shell encapsulating a protein-loaded nanoparticle-based poly(D,L-lactide-co-glycolide) core. This method produces core-shell double-walled microspheres that show controlled protein release and preserved protein bioactivities for 60 days. Based upon these results, we concluded that the core-shell double-walled microspheres might be applied for tissue engineering and therapy for chronic diseases, etc.

&amp;nbsp;Sustained-release G-CSF microspheres using a novel solid-in-oil-in-oil-in-water emulsion method

BackgroundThe main treatments for cancers are still chemotherapy and radiotherapy for intermediate-stage cancer and terminal cancer. However, the therapeutic methods often result in a decreased neutrophilic granulocyte count and other side effects. In this study, in order to improve the neutrophilic granulocyte levels in the blood after radiotherapy and chemotherapy, we developed a sustained-release granulocyte colony–stimulating factor (G-CSF) microsphere formulation using a novel solid-in-oil-in-oil-in-water (S/O/O/W) emulsification method.MethodsG-CSF was loaded into dextran nanoparticles by freezing-induced phase separation, and then the G-CSF–loaded nanoparticles were encapsulated into sustained-release poly(lactic-co- glycolic acid) microspheres using S/O/O/W emulsification. The control microspheres were also prepared through W/O/W emulsification. The performance of the two microsphere formulations was investigated both in vitro and in vivo.ResultsThe microspheres for the controlled release of G-CSF in a zero-order or near-zero-order pattern were provided for 2 weeks. The in vitro cumulative G-CSF release kept over 90% of its bioactivity, which was proved by a NFS-60 cell line growth assay. The microspheres of the control group fabricated by W/O/W emulsification maintained less then half of its bioactivity. The in vivo efficacy of microspheres made using the S/O/O/W method was higher than those using the W/O/W method.ConclusionThese results suggested that the microspheres prepared by the S/O/O/W method had increased neutrophil activity compared to those prepared by W/O/W.

89Zr-Labeled Dextran Nanoparticles Allow in Vivo Macrophage Imaging

Tissue macrophages play a critical role both in normal physiology and in disease states. However, because of a lack of specific imaging agents, we continue to have a poor understanding of their absolute numbers, flux rates, and functional states in different tissues. Here, we describe a new macrophage specific positron emission tomography imaging agent, labeled with zirconium-89 ((89)Zr), that was based on a cross-linked, short chain dextran nanoparticle (13 nm). Following systemic administration, the particle demonstrated a vascular half-life of 3.9 h and was found to be located primarily in tissue resident macrophages rather than other white blood cells. Subsequent imaging of the probe using a xenograft mouse model of cancer allowed for quantitation of tumor-associated macrophage numbers, which are of major interest in emerging molecular targeting strategies. It is likely that the material described, which allows the visualization of macrophage biology in vivo, will likewise be useful for a multitude of human applications.

Preparation and characterization of camptothecin (CPT)-loaded folate-conjugated dextran nanoparticles for tumor-targeted drug delivery using supercritical antisolvent method

Preparation and characterization of camptothecin (CPT)-loaded folate-conjugated dextran nanoparticles for tumor-targeted drug delivery using supercritical antisolvent method

Mannosylated Dextran Nanoparticles: A pH-Sensitive System Engineered for Immunomodulation through Mannose Targeting

Biotherapeutic delivery is a rapidly growing field in need of new materials that are easy to modify, are biocompatible, and provide for triggered release of their encapsulated cargo. Herein, we report on a particulate system made of a polysaccharide-based pH-sensitive material that can be efficiently modified to display mannose-based ligands of cell-surface receptors. These ligands are beneficial for antigen delivery, as they enhance internalization and activation of APCs, and are thus capable of modulating immune responses. When compared to unmodified particles or particles modified with a nonspecific sugar residue used in the delivery of antigens to dendritic cells (DCs), the mannosylated particles exhibited enhanced antigen presentation in the context of major histocompatibility complex (MHC) class I molecules. This represents the first demonstration of a mannosylated particulate system that enables enhanced MHC I antigen presentation by DCs in vitro. Our readily functionalized pH-sensitive material may also open new avenues in the development of optimally modulated vaccine delivery systems.

Sustained-release polylactide-co-glycolide microspheres loaded with pre-formulated protein polysaccharide nanoparticles

Protein-loaded dextran nanoparticles were prepared by the method of freezing-induced phase separation. The average diameter of protein-loaded dextran nanoparticles prepared using this method was between 100 and 300 nm. The protein-loaded dextran nanoparticles were then microencapsulated into polylactide-co-glycolide acid (PLGA) microspheres by the solid-in-oil-in-water (S/O/W) multiple emulsion technique. The release behaviour of the microspheres showed that the method might improve the release profile and bioactivity in vitro, and also reduce initial burst and aggregation. The method will be potentially developed to solve protein-controlled release problems.

Surface modification of crosslinked dextran nanoparticles influences transfection efficiency of dextran–polyethylenimine nanocomposites

Dextran–PEI grafted nanoparticles as transfection agents have been reported, however, with limited success due to their large size, poor buffering capacity and inadequate availability of charge for competent binding to DNA. To address these concerns, dextran was first crosslinked with 1,4-butanediol diglycidyl ether (BDE), a commercially available homobifunctional crosslinker, to form its nanoparticles (DN), which were then partially oxidized with sodium periodate to generate aldehyde functionalities on them. The resultant nanoparticles were grafted with branched polyethylenimine (bPEI, 25 kDa) to obtain a series of DN–PEI nanocomposites (DP), having comparatively smaller size, enhanced buffering capacity and competent binding ability with DNA. Subsequent to biophysical characterization, these nanocomposites were evaluated for their transfection efficiency in serum and serum-free environments and toxicity in various mammalian cell lines. A significantly (p < 0.05) improved transfection efficiency of these nanocomposites concurrent with their minimal cytotoxicity as compared to the selected commercial transfection agents and native PEI was observed. These results were further validated by intracellular trafficking, wherein DP4 (the best working system in the series) was able to carry the DNA inside the nucleus after 1 h of the addition of the complex. The in vivo gene expression profile of the DP4/DNA complex in male Balb/c mice exhibited maximum expression in their spleen tissue raising promise of using these nanocomposites as improved non-viral transfection agents.

Surgical wound healing using hemostatic gauze scaffold loaded with nanoparticles containing sustained-release granulocyte colony-stimulating factor

BackgroundThe therapeutic strategies for malignant melanoma are still cancer chemotherapy, radiotherapy, and tumor resection. However, these therapeutic strategies often lead to a reduced neutrophilic granulocyte count or loss of more blood after surgical tumor resection. In this study, we developed a formulation of hemostatic gauze impregnated with sustained-release granulocyte colony-stimulating factor (G-CSF) with increasing of the neutrophilic granulocyte count in the blood following chemotherapy and decreasing blood loss after surgical tumor resection.MethodsWe designed a formulation with both hemostatic properties and increased neutrophil content to be used in cancer chemotherapy, radiotherapy, and tumor resection, comprising a hemostatic gauze as a scaffold and (G-CSF)-loaded dextran nanoparticles coated with polylactic-co- glycolic acid (PLGA) solution fabricated by direct spray-painting onto the scaffold and then vacuum-dried at room temperature. The performance of this system was evaluated in vitro and in vivo.ResultsNearly zero-order release of G-CSF was recorded for 12–14 days, and the cumulative release of G-CSF retained over 90% of its bioactivity in a NFS-60 cell line proliferation assay when the scaffold was incubated in phosphate-buffered saline (pH 7.4) at 37°C. The in vivo hemostatic efficacy of this formulation was greater than that of native G-CSF, the scaffold directly spray-painted with G-CSF solution or PLGA organic solution as a coating, or when a blank scaffold was covered with the coating.ConclusionOur results suggest that this formulation has both hemostatic properties and increased neutrophil activity.