Rational design of yolk–shell nanostructures for drug delivery

Yolk–shell nanoparticles (YSNPs) are a new class of hollow nanostructures, and their unique properties can be utilized in drug delivery systems. The recent progress in YSNPs-based carriers is highlighted in drug delivery systems. Doxorubicin hydrochloride, ceftriaxone sodium, and methotrexate are three of the most common drugs that are used in this field. According to the reported studies, the materials used most often as yolk–shells are magnetic nanoparticles and polymers. The used methods for synthesizing a diverse array of YSNPs are classified based on their core structures. Various properties of YSNPs include their high drug-loading capacity, and their ability to decrease drug toxicity and satisfactorily and efficiently release drugs.

The recent progress in yolk–shell nanoparticles (YSNPs) as a new class of hollow nanostructures applied for drug delivery.     

A permeation enhancer for increasing transport of therapeutic macromolecules across the intestine

Delivery of therapeutic macromolecules is limited by the physiological limitations of the gastrointestinal tract including poor intestinal permeability, low pH and enzymatic activity. Several permeation enhancers have been proposed to enhance intestinal permeability of macromolecules; however their utility is often hindered by toxicity and limited potency. Here, we report on a novel permeation enhancer, Dimethyl palmitoyl ammonio propanesulfonate (PPS), with excellent enhancement potential and minimal toxicity. PPS was tested for dose- and time-dependent cytotoxicity, delivery of two model fluorescent molecules, sulforhodamine-B and FITC-insulin in vitro, and absorption enhancement of salmon calcitonin (sCT) in vivo. Caco-2 studies revealed that PPS is an effective enhancer of macromolecular transport while being minimally toxic. TEER measurements in Caco-2 monolayers confirmed the reversibility of the effect of PPS. Confocal microscopy studies revealed that molecules permeate via both paracellular and transcellular pathways in the presence of PPS. In vivo studies in rats showed that PPS enhanced relative bioavailability of sCT by 45-fold after intestinal administration. Histological studies showed that PPS does not induce damage to the intestine. PPS is an excellent permeation enhancer which provides new opportunities for developing efficacious oral/intestinal delivery systems for therapeutic macromolecules.     

Liposome-based nanocapsules for the controlled release of dietary curcumin: PDDA and silica nanoparticle-coated DMPC liposomes enhance the fluorescence efficiency and anticancer activity of curcumin

Nanosystems with various compositions and biological properties are being extensively investigated for drug and gene delivery applications. Many nanotechnology methods use novel nanocarriers, such as liposomes, in therapeutically targeted drug delivery systems. However, liposome matrices suffer from several limitations, including drug leakage and instability. Therefore, the surface modification of liposomes by coating them or adding polymers has advanced their application in drug delivery. Hence, the prevention of drug release from the liposome bilayers was the main focus of this work. For this purpose, liposomes were synthesized according to a thin film hydration method by applying various surface modifications. Three different nanocapsules, N1, N2, and N3, were prepared using 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), poly(diallyldimethylammonium)chloride (PDAA) polymer, and silica nanoparticles. PDDA and silica nanoparticles were coated on the surface of liposomes using a layer-by-layer assembly method, completely encapsulating curcumin into the core of the liposome. Fluorescence spectroscopy, TGA, DLS, XRD, SEM, and zeta potential methods were used to characterize the prepared nanocapsules. Interestingly, the fluorescence of curcumin showed a blue shift and the fluorescence efficiency was extraordinarily enhanced ∼25-, ∼54-, and ∼62-fold in the N1, N2, and N3 nanocapsules, respectively. Similarly, encapsulation efficiency, drug loading, and the anticancer activity of dietary curcumin were investigated for the different types of DMPC nanocapsules. The drug efficiencies of the liposomes were established according to the release of curcumin from the liposomes. The results showed that the release of curcumin from the nanocapsules decreased as the number of layers at the surface of the liposomes increased. The release of curcumin follows the Higuchi model; thus, a slow rate of diffusion is observed when a number of layers is added. The better encapsulation and higher anti-cancer activity of curcumin were also observed when more layers were added, which is due to electrostatic interactions inhibiting curcumin from being released.

Nanosystems with various compositions and biological properties are being extensively investigated for drug and gene delivery applications.     

Enhanced intestinal absorption of salmon calcitonin (sCT) from proliposomes containing bile salts.

PURPOSE: The feasibility of using proliposomes containing salmon calcitonin (sCT) and absorption enhancing agents, as an oral delivery system, to improve the intestinal absorption of sCT was explored using rats and Caco-2 cell systems. METHODS: Seventeen surfactants were examined for their effects with reference to accelerating the permeability of sCT (300 microg/ml) across Caco-2 cell monolayers, and damage to the intestinal epithelial cells, as measured by the change in transepithelial electrical resistance (TEER) across the cell monolayer. Proliposomes containing sCT (0.75%, w/w) and sodium taurodeoxycholate (NaTDC, 2.5%, w/w) (TDC proliposomes) were prepared according to the standard method using sorbitol and phosphatidylcholine as core and wall-forming materials, respectively, administered intra-duodenally to rats, and plasma concentrations of sCT were subsequently determined by LC-MS. RESULTS: Among the surfactants examined, some bile salts including NaTDC appeared to be the most advantageous when estimated based on the balance between the permeation enhancement (e.g., a 10.8-fold increase in the permeability of sCT for 0.1% NaTDC) and damage to the cells (e.g., a 3.55-fold decrease in the TEER value for 0.1% NaTDC). The administration of TDC proliposomes resulted in a 7.1-fold increase in the bioavailability (i.e., 0.49%) of sCT, when administered duodenally to rats. The size of the reconstituted liposomes in water was significantly smaller (e.g., 23.2 nm, number weighted diameter), and the entrapment efficiency (EE) of sCT in the reconstituted liposomes was 2.8-fold larger (54.9%), for TDC proliposomes, compared to proliposomes prepared without NaTDC (sCT proliposomes). CONCLUSION: A 7.1-fold increase in the bioavailability of sCT could be achieved from the TDC proliposomes. In addition to the intrinsic activity of the bile salt to fluidize the membrane, the simultaneous delivery of sCT and NaTDC to the site of absorption in the intestine via proliposomes and the subsequent formation of lipophilic ion-pair complexes between sCT and NaTDC at the site might have been contributing factors in this outstanding absorption enhancement.     

Liposome-entrapped ampicillin in the treatment of experimental murine listeriosis and salmonellosis.

The tissue distribution of ampicillin entrapped in liposomes was studied in normal noninfected mice and showed that ampicillin concentrated mostly in the liver and spleen. Liposomate ampicillin was significantly more effective than free ampicillin in reducing splenic and hepatic bacterial counts in C57BL/Ka nude mice chronically infected with Listeria monocytogenes EGD. It was also significantly more effective than free ampicillin in reducing mortality in C57BL/6 mice acutely infected with Salmonella typhimurium C5. Comparison of the results with those previously obtained in the same experimental models with the same amounts of ampicillin bound to polyisohexylcyanoacrylate nanoparticles showed that liposomes were more effective than nanoparticles (M. Youssef, E. Fattal, M. J. Alonso, L. Roblot-Treupel, J. Sauzières, C. Tancrède, A. Omnès, P. Couvreur, and A. Andremont, Antimicrob. Agents Chemother. 32:1204-1207, 1988) in targeting ampicillin to the spleen but were less effective than nanoparticles in targeting ampicillin to the liver and reducing mortality in acute salmonellosis.     

The effect of electroporation on iontophoretic transdermal delivery of calcium regulating hormones.

Electrically-assisted delivery by iontophoresis and/or electroporation was used in vitro to deliver the calcium regulating hormones, salmon calcitonin (sCT) and parathyroid hormone (1-34) (PTH) through human epidermis. Such delivery could be useful for chronic treatment of post-menopausal osteoporosis and other clinical indications as a superior alternative to parenteral delivery. sCT (50 microg/ml) or PTH (1-34) (100 microg/ml) formulation was prepared in citrate buffer (pH 4.0 or 5.0, respectively). Epidermis separated from human cadaver skin was used. Iontophoresis was applied using a constant current power source and electroporation with an exponential pulse generator. Silver/silver chloride electrodes were used. A combination of electroporation and iontophoresis resulted in higher transdermal permeation than either one technique alone. Electroporation also shortened the lag time of iontophoretic transdermal delivery of salmon calcitonin. Pulsing at lower voltages followed by iontophoresis did not result in increased transport (over iontophoresis alone), perhaps because the transdermal voltage was very low. The transdermal transport of salmon calcitonin by pulsing with 15 pulses (1 ppm) of 500 V (200 ms) followed by iontophoresis led to a quick input and high flux. The average transdermal voltage was only about 50 V for a 500 V study.     

A brief review on solid lipid nanoparticles: part and parcel of contemporary drug delivery systems

Drug delivery technology has a wide spectrum, which is continuously being upgraded at a stupendous speed. Different fabricated nanoparticles and drugs possessing low solubility and poor pharmacokinetic profiles are the two major substances extensively delivered to target sites. Among the colloidal carriers, nanolipid dispersions (liposomes, deformable liposomes, virosomes, ethosomes, and solid lipid nanoparticles) are ideal delivery systems with the advantages of biodegradation and nontoxicity. Among them, nano-structured lipid carriers and solid lipid nanoparticles (SLNs) are dominant, which can be modified to exhibit various advantages, compared to liposomes and polymeric nanoparticles. Nano-structured lipid carriers and SLNs are non-biotoxic since they are biodegradable. Besides, they are highly stable. Their (nano-structured lipid carriers and SLNs) morphology, structural characteristics, ingredients used for preparation, techniques for their production, and characterization using various methods are discussed in this review. Also, although nano-structured lipid carriers and SLNs are based on lipids and surfactants, the effect of these two matrixes to build excipients is also discussed together with their pharmacological significance with novel theranostic approaches, stability and storage.

Drug delivery technology has a wide spectrum, which is continuously being upgraded at a stupendous speed.     

Mucoadhesive intestinal devices for oral delivery of salmon calcitonin

One of the major challenges faced by therapeutic polypeptides remains their invasive route of delivery. Oral administration offers a potential alternative to injections; however, this route cannot be currently used for peptides due to their limited stability in the stomach and poor permeation across the intestine. Here, we report mucoadhesive devices for oral delivery that are inspired by the design of transdermal patches and demonstrate their capabilities in vivo for salmon calcitonin (sCT). The mucoadhesive devices were prepared by compressing a polymeric matrix containing carbopol, pectin and sodium carboxymethylcellulose (1:1:2), and were coated on all sides but one with an impermeable and flexible ethyl cellulose (EC) backing layer. Devices were tested for in vitro dissolution, mucoadhesion to intestinal mucosa, enhancement of drug absorption in vitro (Caco-2 monolayer transport) and in vivo in rats. Devices showed steady drug release with ≈ 75% cumulative drug released in 5 h. Devices also demonstrated strong mucoadhesion to porcine small intestine to withstand forces up to 100 times their own weight. sCT-loaded mucoadhesive devices exhibited delivery of sCT across Caco-2 monolayers and across the intestinal epithelium in vivo in rats. A ≈ 52-fold (pharmacokinetic) and ≈ 44-fold (pharmacological) enhancement of oral bioavailability was observed with mucoadhesive devices when compared to direct intestinal injections. Oral delivery of devices in enteric coated capsules resulted in significant bioavailability enhancement.     

Systemic peptide delivery via the stomach: in vivo evaluation of an oral dosage form for salmon calcitonin.

It was the aim of this study to investigate the potential of stomach targeted delivery systems for systemic peptide administration using salmon calcitonin as a model drug. Chitosan was modified by the immobilization of thiol groups utilizing 2-iminothiolane in order to obtain a chitosan-4-thiobutylamidine conjugate (chitosan-TBA). Furthermore, a chitosan-pepstatin A conjugate was synthesized by a carbodiimide mediated linkage of the pepsin inhibitor to the polymer. The protective effect of this novel conjugate for calcitonin towards pepsin was evaluated in vitro. Minitablets (5 mg) were generated by direct compression of calcitonin, chitosan, chitosan-TBA, chitosan-pepstatin A conjugate and glutathione (GSH), respectively (A, 1:0:69:20:10; B, 1:79:0:20:0; C, 1:99:0:0:0). The drug release was investigated in an artificial gastric fluid. Biofeedback studies were performed in rats by determining the decrease in plasma calcium level after oral administration. The novel chitosan-pepstatin A conjugate displayed 291+/-58 nmol inhibitor per gram polymer (mean+/-S.D., n = 5). The chitosan-inhibitor conjugate showed a very strong protective effect for salmon calcitonin towards pepsinic degradation. A controlled drug release was provided by all tested dosage forms-A, B and C. Dosage form B led only to a slight reduction of the plasma calcium level, displaying a pharmacological efficacy versus i.v. injection of 0.41%, while dosage form C did not lead to any significant effect. In contrast, dosage form A led to a decrease in the plasma calcium level of 10% for at least 12 h. The pharmacological efficacy of this formulation was determined to be 1.35%. The study suggests that stomach targeted oral delivery might be a promising novel approach for noninvasive systemic peptide administration.     

Preparation and characterization of emamectin benzoate nanoformulations based on colloidal delivery systems and use in controlling Plutella xylostella (L.) (Lepidoptera: Plutellidae)

Colloidal delivery systems have been widely used as carriers for controlled delivery of pesticides to improve the efficacy and photostability of natural and semi-synthetic pesticides. In this study, we have synthesized emamectin benzoate nanoformulations (EB + NFs) depending on polymeric nanocapsules (PNC) and two types of the nanosilica, mesoporous nanosilica (MCM-48) and silicon dioxide nanoparticles (SNPs) as carriers for the emamectin benzoate (EB). The fabricated nanoformulations were characterized by using X-ray diffraction analysis, Fourier transform infrared spectroscopy, particle size, zeta potential, morphology, absolute recovery (AR), entrapment efficiency (EE), UV stability and release kinetics. The obtained results showed that the carriers had a remarkable loading ability for EB and improved the EB photostability. The EE% of nanoformulations were 92.84%, 87.45% and 71.19% for emamectin benzoate polymeric nanocapsules (EB + PNC), emamectin benzoate SNPs (EB + SNPs) and emamectin benzoate MCM-48 (EB + MCM-48) respectively. The insecticidal activity of EB + NFs against Plutella xylostella showed that the EB + SNPs was more effective than other EB + NFs and EB alone. The LC₅₀ values were 0.18, 4.03, 8.49 and 11.06 mg L⁻¹ for EB + SNPs, EB + MCM-48, EB + PNC and EB respectively. The obtained results suggest the colloidal delivery systems that used in this study could improve the efficacy and photostability for EB, and they are able to overcome the disadvantage of the natural and semi-synthetic pesticides such as environmental sensitivity and to increase the efficacy of pesticides, which eventually leads to reduce the dosage of pesticides needed, reducing the number of applications required in comparison to conventional formulations.

Colloidal delivery systems have been widely used as carriers for controlled delivery of pesticides to improve the efficacy and photostability of natural and semi-synthetic pesticides.     

Design of biodegradable particles for protein delivery.

Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate protein carriers in order to overcome mucosal barriers. We have attempted to combine both issues through the conception of new biodegradable polymer nanoparticles: (i) poly(ethylene glycol) (PEG)-coated poly(lactic acid) (PLA) nanoparticles, chitosan (CS)-coated poly(lactic acid-glycolic acid (PLGA) nanoparticles and chitosan (CS) nanoparticles. These nanoparticles have been tested for their ability to load proteins, to deliver them in an active form, and to transport them across the nasal and intestinal mucosae. Additionally, the stability of some of these nanoparticles in simulated physiological fluids has been studied. Results showed that the PEG coating improves the stability of PLA nanoparticles in the gastrointestinal fluids and helps the transport of the encapsulated protein, tetanus toxoid, across the intestinal and nasal mucosae. Furthermore, intranasal administration of these nanoparticles provided high and long-lasting immune responses. On the other hand, the coating of PLGA nanoparticles with the mucoadhesive polymer CS improved the stability of the particles in the presence of lysozyme and enhanced the nasal transport of the encapsulated tetanus toxoid. Finally, nanoparticles made solely of CS were also stable upon incubation with lysozyme. Moreover, these particles were very efficient in improving the nasal absorption of insulin as well as the local and systemic immune responses to tetanus toxoid, following intranasal administration. In summary, these results show that a rational modification in the composition and structure of the nanoparticles, using safe materials, increases the prospects of their usefulness for mucosal protein delivery and transport.     

PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination

To improve the efficiency of orally delivered vaccines, PEGylated PLGA-based nanoparticles displaying RGD molecules at their surface were designed to target human M cells. RGD grafting was performed by an original method called “photografting” which covalently linked RGD peptides mainly on the PEG moiety of the PCL–PEG, included in the formulation. First, three non-targeted formulations with size and zeta potential adapted to M cell uptake and stable in gastro-intestinal fluids, were developed. Their transport by an in vitro model of the human Follicle associated epithelium (co-cultures) was largely increased as compared to mono-cultures (Caco-2 cells). RGD-labelling of nanoparticles significantly increased their transport by co-cultures, due to interactions between the RGD ligand and the β₁ intregrins detected at the apical surface of co-cultures. In vivo studies demonstrated that RGD-labelled nanoparticles particularly concentrated in M cells. Finally, ovalbumin-loaded nanoparticles were orally administrated to mice and induced an IgG response, attesting antigen ability to elicit an immune response after oral delivery.     

Calcium carbonate nanowires: greener biosynthesis and their leishmanicidal activity

The synthesis of inorganic rod shape nanostructures is important in chromatography, dentistry, and medical applications such as bone implants, and drug and gene delivery systems. Herein, calcium carbonate (CaCO₃) nanowires were synthesized using a plant extract and the ensuing nanoparticles were characterized by XRD, FESEM, and HR-TEM. Then, the leishmanicidal effects of biogenic calcium carbonate nanowires were investigated against Leishmania major including the toxicity of varying concentrations of nanoparticles, and the percentage of viable and apoptotic cells based on flow cytometry analysis. Based on the results, the IC₅₀ of these polymorphs were calculated to be 800 μg mL⁻¹. An ecofriendly, inexpensive, and novel biogenic method for the production of a new advanced inorganic nanostructure, CaCO₃ nanowires, is described without using hazardous chemicals; calcium carbonate nanowires maybe used as a smart drug carrier.

The synthesis of inorganic rod shape nanostructures is important in chromatography, dentistry, and medical applications such as bone implants, and drug and gene delivery systems.     

Lipid-based nanoparticles for psoriasis treatment: a review on conventional treatments,recent works,and future prospects

Psoriasis is a lingering inflammatory skin disease that attacks the immune system. The abnormal interactions between T cells, immune cells, and inflammatory cytokines causing the epidermal thickening. International guidelines have recommended topical treatments for mild to moderate psoriasis whilst systemic and phototherapy treatments for moderate to severe psoriasis. However, current therapeutic approaches have a wider extent to treat moderate to severe type of psoriasis especially since the emergence of diverse biologic agents. In the meantime, topical delivery of conventional treatments has prompted many unsatisfactory effects to penetrate through the skin (stratum corneum). By understanding the physiology of stratum corneum barrier functions, scientists have developed different types of lipid-based nanoparticles like solid lipid nanoparticles, nanostructured lipid carriers, nanovesicles, and nanoemulsions. These novel drug delivery systems help the poorly solubilised active pharmaceutical ingredient reaches the targeted site seamlessly because of the bioavailability feature of the nanosized molecules. Lipid-based nanoparticles for psoriasis treatments create a paradigm for topical drug delivery due to their lipids'' amphiphilic feature to efficiently encapsulate both lipophilic and hydrophilic drugs. This review highlights different types of lipid-based nanoparticles and their recent works of nano formulated psoriasis treatments. The encapsulation of psoriasis drugs through lipid nanocarriers unfold numerous research opportunities in pharmaceutical applications but also draw challenges for the future development of nano drugs.

Lipid-based nanoparticles are lipidic nanocarriers that can encapsulate different antipsoriatic agents for topical uses, which enhance the alleviation process compared to conventional topical agents (without nanocarriers).     

Bacterial ghosts as novel advanced drug delivery systems: antiproliferative activity of loaded doxorubicin in human Caco-2 cells.

Systemic application of anticancer drugs often causes severe toxic side effects. To reduce the undesired effects, advanced drug delivery systems are needed which are based on specific cell targeting vehicles. In this study, bacterial ghosts from Mannheimia haemolytica were used for site-specific delivery of doxorubicin (DOX) to human colorectal adenocarcinoma cells (Caco-2). Bacterial ghosts are non-denatured envelopes of Gram-negative bacteria with fully intact surface structures for specific attachment to mammalian cells. The in vitro release profile of DOX-ghosts demonstrated that the loaded drug was non-covalently associated with the bacterial ghosts and that the drug delivery vehicles themselves represent a slow release system. Adherence studies showed that the M. haemolytica ghosts more efficiently than E. coli ghosts targeted the Caco-2 cells and released the loaded DOX within the cells. Cytotoxicity assays revealed that the DOX-ghosts exhibited potent antiproliferative activities on Caco-2 cells as the DOX associated with ghosts was two magnitude of orders more cytotoxic than free DOX provided in the medium at the same concentrations. Notably, a significant reduction in the cell viability was measured with DOX-ghosts at low DOX concentrations, which had no inhibitory effect when applied as free DOX after incubation for 16 h or when applied at higher concentrations for only 10 min to the cells. As the higher antiproliferative effects of DOX on Caco-2 cells were mediated by the specific drug targeting properties of the bacterial ghosts, the bacterial ghost system represents a novel platform for advanced drug delivery.     

Chitosan magnetic nanoparticles for pH responsive Bortezomib release in cancer therapy

The use of nanotechnology in cancer treatment offers exciting opportunities, including the possibility of destroying tumors with minimal damage to healthy tissue by novel targeted drug delivery systems. pH differences between healthy and tumor microenvironment provide pH responsive release of drugs at tumor site via smart nanoparticles. In this study, chitosan coated superparamagnetic iron oxide nanoparticles (CS MNPs) were in situ synthesized by ionic crosslinking method as nanocarrier systems and loaded with the drug Bortezomib (Velcade^®). The drug loading capacity, drug release and stability of CS MNPs were analyzed. CS MNPs were visualized inside the cells by fluorescence microscopy. The cytotoxicity of Bortezomib, CS MNPs and Bortezomib loaded CS MNPs were tested by XTT analyses in vitro. Gene expression analyses revealed that pro-apoptotic PUMA and NOXA genes were upregulated while anti-apoptotic BCL-2, SURVIVIN and cIAP-2 genes were downregulated at Bortezomib loaded CS MNP treated cells. Immunocytochemical analyses demonstrated an increase in p53 tumor suppressor protein levels at treated cells, which supports the upregulation of PUMA and NOXA genes, while Survivin protein level did not significantly change. This study points out that the pH responsive magnetic targeting of Bortezomib is more efficacious than free drug treatment. Moreover, targeted delivery of Bortezomib would reduce the frequency of drug administration by lowering the required amount of drug dose.     

The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy.

The efficacy of intranasal salmon calcitonin was examined in a double-blind randomized study in reflex sympathetic dystrophy. Sixty-six patients were randomly divided in two groups receiving physiotherapy. In addition group I also received 3 x 100 U/day of salmon calcitonin by intranasal spray whereas group II received 3 sprays of placebo. The pain and the range of motion were improved by calcitonin administration. Similarly the patients' ability to work was also improved. The results confirmed that salmon calcitonin has an effect but that this effect was not equally observed on all parameters analyzed. It was most marked on pain (at rest and on movement) and on the ability to work.     

Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer cells through contact-mediated mechanisms: implications for enhanced local drug delivery

Liquid perfluorocarbon nanoparticles serve as sensitive and specific targeted contrast and drug delivery vehicles by binding to specific cell surface markers. We hypothesized that application of acoustic energy at diagnostic power levels could promote nanoparticle-associated drug delivery by stimulating increased interaction between the nanoparticle's lipid layer and the targeted cell's plasma membrane. Ultrasound (mechanical index = 1.9) applied with a conventional ultrasound imaging system to nanoparticles targeted to alpha(v)beta3-integrins on C32 melanoma cancer cells in vitro produced no untoward effects. Within 5 min, lipid delivery from nanoparticles into cell cytoplasm was dramatically augmented. We also demonstrate the operation of a potential physical mechanism for this effect, the acoustic radiation force on the nanoparticles, which may contribute to the enhanced lipid delivery. Accordingly, we propose that local delivery of lipophilic substances (e.g., drugs) from targeted nanoparticles directly into cell cytoplasm can be augmented rapidly and safely with conventional ultrasound imaging devices through nondestructive mechanisms.     

Regulation of microglia polarization via mannose receptor-mediated delivery of siRNA by ligand-functionalized DoGo LNP

The pro-inflammatory polarization of microglia after stroke is one of the major causes of secondary brain injury. Downregulation of the gene involved in canonical inflammatory pathways in glial cells can exert neuroprotective effects via inhibiting the release of pro-inflammatory factors. In this study, we functionalized DoGo lipids with mannose, the ligand of the mannose receptor (MR) that is expressed in microglia, and evaluated the MR-mediated cellular internalization of DoGo lipid nanoparticles (denote M3) carrying siRNA against TLR4 in BV2 cells in vitro. We confirmed that siTLR4/M3 complexes were specifically internalized by BV2 cells in a MR-dependent manner, and the treatment of oxygen glucose deprivation (OGD)-treated BV2 cells with siTLR4/M3 complexes resulted in remarkable silencing of TLR4, and induced downregulated M1 polarization and upregulated M2 polarization markers. Collectively, our data suggest that the M3 lipoplex is a promising microglia-targeting siRNA delivery agent.

Mannose functionalized DoGo lipid nanoparticles (denote M3) can effectively deliver siRNA to microglia via receptor-mediated internalization, knockdown target gene and induce neuroprotective M2 polarization.     

Treatment of migraine with salmon calcitonin: effects on plasma beta-endorphin, ACTH and cortisol levels

In this study we have examined the results of salmon calcitonin treatment on migraine pain. The mechanism by which calcitonin induces analgesia is still not understood. We observed the effect of a 5-day treatment with salmon calcitonin (IM 100 IU/day) on circulating levels of beta-endorphin, ACTH, and cortisol in 20 patients with migraine during the headache-free period. All 3 hormones were increased after the calcitonin administration and the maximum increase was obtained in beta-endorphin levels. There were significant statistical correlations between beta-endorphin, ACTH, and cortisol levels determined before and after calcitonin treatment.