Trinitroglycerin-loaded chitosan nanogels accelerate angiogenesis in wound healing process.

Trinitroglycerin (TNG) with remarkable angiogenic, antibacterial, and antioxidative activity is a promising candidate to govern wound healing capacity. However, its clinical administration is limited due to associated complications and NO short half-life. In the current study, TNG-loaded chitosan nanogels (TNG-Ngs) were examined in-vitro and in-vivo to gain insight into their clinical application. We prepared TNG-Ngs and characterized their physiochemical properties. The potential of TNG-Ngs was assessed using biocompatibility, scratch assay, and a full-thickness skin wounds model, followed by histopathological and immunohistochemistry examinations. TNG-Ngs particle size 96 ± 18 and definite size distribution histogram. The loading capacity (LC) and encapsulation efficiency (EE) of prepared TNG-Ngs were 70.2 % and 2.1 %, respectively. The TNG-Ngs samples showed enhanced migration of HUVECs with no apparent cytotoxicity. The topical use of TNG-Ngs200 on the wounds revealed a complete wound closure ratio, skin component formation, less scar width, remarkable granulation tissue, promoted collagen deposition, and enhanced the relative mean density of α-SMA and CD31. TNG-Ngs accelerated wound healing by promoting collagen deposition and angiogenic activity, as well as reducing inflammation. The findings indicated that TNG-Ngs is expected to be well vascularized in the wound area and to be more effective in topical therapy.

Trinitroglycerin-loaded chitosan nanogels: Shedding light on cytotoxicity, antioxidativity, and antibacterial activities.

AIM AND BACKGROUND: Trinitroglycerin (TNG) is a remarkable NO-releasing agent. Here, we synthesized TNG based on chitosan Nanogels (Ngs) for ameliorating complications associated with high-dose TNG administration. METHOD: TNG-Ngs fabricated through ionic-gelation technique. Fourier-transformed infrared (FT-IR), zeta-potential, dynamic light scattering (DLS), and electron microscopy techniques evaluated the physicochemical properties of TNG-Ngs. MTT was used to assess the biocompatibility of TNG-Ngs, as the antioxidative properties were determined via lactate dehydrogenase (LDH), reactive oxygen species (ROS), and lipid peroxide (LPO) assays. The antibacterial activity was evaluated against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE). RESULTS: Physicochemical characterization reveals that TNG-Ngs with size diameter (96.2 ± 29 nm), polydispersity index (PDI, 0.732), and negative zeta potential (-1.1 mv) were fabricated. The encapsulation efficacy (EE) and loading capacity (LC) were obtained at 71.1 % and 2.3 %, respectively, with no considerable effect on particle size and morphology. The cytotoxicity assay demonstrated that HepG2 cells exposed to TNG-Ngs showed relative cell viability (RCV) of >80 % for 70 µg/ml compared to the TNG-free drug at the same concentration (P < 0.05). TNG-Ngs showed significant differences with the TNG-free drug for LDH, LPO, and ROS formation at the same concentration (P < 0.001). The antibacterial activity of the TNG-Ngs against S. aureus, E. coli, VRE, and MRSA was higher than the TNG-free drug and Ngs (P < 0.05). CONCLUSION: TNG-Ngs with enhanced antibacterial and antioxidative activity and no obvious cytotoxicity might be afforded as novel nanoformulation for promoting NO-dependent diseases.

Valine conjugated polymeric nanocarriers for targeted co-delivery of rivastigmine and quercetin in rat model of Alzheimer disease.

Multifunctional nanocarriers are increasingly promising for disease treatment aimed at finding effective therapy and overcoming barriers in drug delivery. Herein, valine conjugated chitosan (VLCS) was used for surface modification of nanocarriers (NCs) based on Poly (ε-caprolactone)-Poly (ethylene glycol)-Poly (ε-caprolactone) (PCL-PEG-PCL) triblock copolymers (NCs@VLCS). The nanocarriers were co-loaded with rivastigmine (RV) and quercetin (QT) to yield the final RV/QT-NCs@VLCS as a multifunctional nanocarrier for Alzheimer's disease (AD) treatment. The large amino acid transporter 1 (LAT-1) was selected for the direction of the NCs to the brain. The biocompatibility of the nanocarrier was studied in HEK-293 and SH-SY5Y cells and rats. The Morris water maze test demonstrated a faster regain of memory loss with RV/QT-NCs@VLCS compared to the other groups. Furthermore, RV/QT-NCs@VLCS and RV/QT-NCs improved GSH depletion induced by scopolamine (SCO), with RV/QT-NCs@VLCS having a superior effect. The real-time PCR analysis revealed that co-delivery of RV and QT by NCs@VLCS showed significantly higher efficacy than sole delivery of RV. RV/QT-NCs@VLCS treatment also modulated the expression of BDNF, ACHE, and TNF-α. The findings revealed that NCs@VLCS co-loaded with RV and QT, significantly increased efficacy relative to the single use of RV and could be considered a potent multifunctional drug delivery system for Alzheimer's treatment.

Pharmacokinetics and repeated dose 28-day oral toxicity studies of acetaminophen nanosuspension.

Wide availability and easy accessibility of acetaminophen oral dosage forms increase the risk of intentional poisoning or unintentional organ toxicity, leading to a wide range of liver failure, nephrotoxicity, and neurotoxicity. In this study, an attempt was made to improve oral bioavailability and reduce the toxicity of acetaminophen using nanosuspension technology. The acetaminophen nanosuspensions (APAP-NSs) were prepared by a nano-precipitation method using polyvinyl alcohol and hydroxypropylmethylcellulose as stabilizers. The mean diameter of APAP-NSs was 124 ± 3.8 nm. The dissolution profile of APAP-NSs was significantly point-to-point higher than the coarse drug in simulated gastrointestinal fluids. The in vivo study revealed 1.6- and 2.8-fold increases in the AUC0-inf and Cmax of the drug, respectively, in APAP-NSs-receiving animals compared to the control group. Moreover, no deaths and no abnormalities in clinical signs, body weights, and necropsy findings were detected in the dose groups up to 100 mg/kg of the 28-day repeated oral dose toxicity study in mice.

Enhancing Methotrexate Delivery in the Brain by Mesoporous Silica Nanoparticles Functionalized with Cell-Penetrating Peptide using in Vivo and ex Vivo Monitoring.

The blood-brain barrier (BBB) acts as a physical/biochemical barrier that protects brain parenchyma from potential hazards exerted by different xenobiotics found in the systemic circulation. This barrier is created by "a lipophilic gate" as well as a series of highly organized influx/efflux mechanisms. The BBB bottleneck adversely affects the efficacy of chemotherapeutic agents in treating different CNS malignancies such as glioblastoma, an aggressive type of cancer affecting the brain. In the present study, mesoporous silica nanoparticles (MSNs) were conjugated with the transactivator of transcription (TAT) peptide, a cell-penetrating peptide, to produce MSN-NH-TAT with the aim of improving methotrexate (MTX) penetration into the brain. The TAT-modified nanosystem was characterized by Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and N2 adsorption-desorption analysis. In vitro hemolysis and cell viability studies confirmed the biocompatibility of the MSN-based nanocarriers. In addition, in vivo studies showed that the MTX-loaded MSN-NH-TAT improved brain-to-plasma concentration ratio, brain uptake clearance, and the drug's blood terminal half-life, compared with the use of free MTX. Taken together, the results of the present study indicate that MSN functionalization with TAT is crucial for delivery of MTX into the brain. The present nanosystem represents a promising alternative drug carrier to deliver MTX into the brain via overcoming the BBB.

Titanium-Based Nanoarchitectures for Sonodynamic Therapy-Involved Multimodal Treatments.

Sonodynamic therapy (SDT) has considerably revolutionized the healthcare sector as a viable noninvasive therapeutic procedure. It employs a combination of low-intensity ultrasound and chemical entities, known as a sonosensitizer, to produce cytotoxic reactive oxygen species (ROS) for cancer and antimicrobial therapies. With nanotechnology, several unique nanoplatforms are introduced as a sonosensitizers, including, titanium-based nanomaterials, thanks to their high biocompatibility, catalytic efficiency, and customizable physicochemical features. Additionally, developing titanium-based sonosensitizers facilitates the integration of SDT with other treatment modalities (for example, chemotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy, and immunotherapy), hence increasing overall therapeutic results. This review summarizes the most recent developments in cancer therapy and tissue engineering using titanium nanoplatforms mediated SDT. The synthesis strategies and biosafety aspects of Titanium-based nanoplatforms for SDT are also discussed. Finally, various challenges and prospects for its further development and potential clinical translation are highlighted.

Polysorbate-coated mesoporous silica nanoparticles as an efficient carrier for improved rivastigmine brain delivery.

Targeted delivery of neurological therapeutic to the brain has been attracting more and more attention to the treatment of central nervous system (CNS) diseases. Nonetheless, the main obstacle in this road map is the existence of a blood-brain barrier (BBB) which limits the penetration efficiency of most CNS drugs into the brain parenchyma. This present investigation describes a facile synthetic strategy to prepare a highly biocompatible calcium-doped mesoporous silica nanoparticles (MSNs) functionalized by polysorbate-80 (PS) as targeting ligand to deliver rivastigmine (RV) into the brain via crossing the BBB. The developed nanosystem was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), Zeta potential, and N2-adsorption-desorption analysis. In vitro hemolysis studies were carried out to confirm the biocompatibility of the nanocarriers. Our in vivo studies in an animal model of rats showed that the RV-loaded nanosystem was able to enhance the brain-to-plasma concentration ratio, brain uptake clearance, and plasma elimination half-life of the drug compared to the free one drug following intravenous (IV) administration. The results revealed that functionalization of MSNs by PS is crucial to deliver RV into the brain, suggesting PS-functionalized MSNs could be an effective carrier to deliver RV to the brain while overcoming BBB.

Surface modification of neurotrophin-3 loaded PCL/chitosan nanofiber/net by alginate hydrogel microlayer for enhanced biocompatibility in neural tissue engineering.

This study prepared a novel three-dimensional nanocomposite scaffold by the surface modification of PCL/chitosan nanofiber/net with alginate hydrogel microlayer, hoping to have the privilege of both nanofibers and hydrogels simultaneously. Bead free randomly oriented nanofiber/net (NFN) structure composed of chitosan and polycaprolactone (PCL) was fabricated by electrospinning method. The low surface roughness, good hydrophilicity, and high porosity were obtained from the NFN structure. Then, the PCL/chitosan nanofiber/net was coated with a microlayer of alginate containing neurotrophin-3 (NT-3) and conjunctiva mesenchymal stem cells (CJMSCs) as a new stem cell source. According to the cross-sectional FESEM, the scaffold shows a two-layer structure with interconnected pores in the range of 20 µm diameter. The finding revealed that the surface modification of nanofiber/net by alginate hydrogel microlayer caused lower inflammatory response and higher proliferation of CJMSCs than the unmodified scaffold. The initial burst release of NT-3 was 69% in 3 days which followed by a sustained release up to 21 days. The RT-PCR analysis showed that the expression of Nestin, MAP-2, and ß-tubulin III genes were increased 6, 5.4, and 8.8-fold, respectively. The results revealed that the surface-modified biomimetic scaffold possesses enhanced biocompatibility and could successfully differentiate CJMSCs to the neuron-like cells.

Enhancement of the brain delivery of methotrexate with administration of mid-chain ester prodrugs: In vitro and in vivo studies.

In the present study, with the aim of improving the permeability of methotrexate (MTX) to the brain, the lipophilic MTX prodrugs containing the ester functional moiety were synthesized. The chemical structure of synthesized prodrugs was characterized and confirmed by FT-IR, NMR and mass spectral studies. Based on the results of in vitro cytotoxic studies, all of the synthesized prodrugs led to decrease in the IC50 in 72 h on U87 cancer cell line and the best result was observed for dihexyl methotrexate (MTX-DH) in comparison with free MTX, which led to decrease the IC50 amount up to 6 folds. In addition, in vivo toxicity on Artemia salina (A. salina) showed that the lipophilic MTX prodrugs have been able to partially mask the toxic profile of free MTX, at the same concentrations. These findings were also in compliance with hemolysis assay results, which confirm that the conjugates has not made the drug more toxic. Furthermore, in vivo study in rat model, was employed to determine the simultaneous drug concentration in brain and plasma. According to the obtained results, the brain-to-plasma concentration ratios (Kp values) of MTX-DH and dioctyl methotrexate (MTX-DO) groups were significantly higher compared with free MTX. Moreover, the uptake clearance of MTX by brain parenchyma increased significantly (3.85 and 9.08-time increased for MTX-DH and MTX-DO prodrugs, respectively). These findings indicate that the synthesized lipophilic MTX prodrugs are non-toxic and able to enhance brain penetration of MTX.

Fabrication of ciprofloxacin-loaded chitosan/polyethylene oxide/silica nanofibers for wound dressing application: In vitro and in vivo evaluations.

Silica plays an effective role in collagen creation; hence, the degradation products of silica-based materials accelerate wound healing. In this regard, chitosan/polyethylene oxide/silica hybrid nanofibers were prepared by the combining the sol-gel method with electrospinning technique to accelerate the wound healing process. Ciprofloxacin, as an antibacterial drug, was then added to the electrospinning mixture. The nanofibers were characterized by SEM, EDX, X-ray mapping, TEM, TGA, FTIR, and XRD analysis. The degradation, swelling ratio, and release of ciprofloxacin were investigated in PBS. The prepared nanofiber could absorb water, maintain its morphological integrity during the degradation process, and gradually release ciprofloxacin. The nanofibers revealed an efficient antibacterial activity against Escherichia coli and Staphylococcus aureus. Cell viability assays showed that the nanofibers had no cytotoxicity against L929 mouse fibroblast and HFFF2 human foreskin fibroblast cell lines. The potential of the chitosan/polyethylene oxide/silica/ciprofloxacin nanofiber for healing full-thickness wound was assessed by applying the scaffold in the dorsal cutaneous wounds of the Balb/C mice. The white blood cell counts of the animals indicated the nanofiber-treated mice compared with the untreated ones had less infection and inflammation. According to the histopathologic data, the prepared nanofiber accelerated and enhanced tissue regeneration by increasing fibroblast cells and angiogenesis as well as decreasing the inflammation phase. The findings suggest that the prepared antibacterial scaffold with drug delivery properties could be an appropriate candidate for many medical and hygienic applications, especially as a bio-compatible and bio-degradable wound dressing.

Emerging insights on drug delivery by fatty acid mediated synthesis of lipophilic prodrugs as novel nanomedicines.

Many drug molecules that are currently in the market suffer from short half-life, poor absorption, low specificity, rapid degradation, and resistance development. The design and development of lipophilic prodrugs can provide numerous benefits to overcome these challenges. Fatty acids (FAs), which are lipophilic biomolecules constituted of essential components of the living cells, carry out many necessary functions required for the development of efficient prodrugs. Chemical conjugation of FAs to drug molecules may change their pharmacodynamics/pharmacokinetics in vivo and even their toxicity profile. Well-designed FA-based prodrugs can also present other benefits, such as improved oral bioavailability, promoted tumor targeting efficiency, controlled drug release, and enhanced cellular penetration, leading to improved therapeutic efficacy. In this review, we discuss diverse drug molecules conjugated to various unsaturated FAs. Furthermore, various drug-FA conjugates loaded into various nanostructure delivery systems, including liposomes, solid lipid nanoparticles, emulsions, nano-assemblies, micelles, and polymeric nanoparticles, are reviewed. The present review aims to inspire readers to explore new avenues in prodrug design based on the various FAs with or without nanostructured delivery systems.

Effect of Colloidal Aqueous Solution of Fullerene (C60) in the Presence of a P-Glycoprotein Inhibitor (Verapamil) on Spatial Memory and Hippocampal Expression of Sirtuin6, SELADIN1, and AQP1 Genes in a Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common types of neurodegenerative diseases which is accompanied by irreversible neuronal damage, learning difficulties, memory impairments, and cognitive disorders. The cholinergic system is destroyed during AD pathogenesis, leading to the major symptoms of the disease. Although in severe stages AD is life threatening, to date no absolute treatment has been found for this illness and some palliative options are available. The aim of this study was to investigate the effect of fullerene (C60) aqueous suspension (FAS) on improving spatial memory in amnesic male Wistar rats (weighing 200 ± 20 g) and to further compare the results with that of donepezil (DNPZL) as a standard drug. FAS was prepared via a solvent exchange method. The particle size was in the 119.14 ± 3.38 nm range with polydispersity index of 0.15 ± 0.02 and zeta potential of -12.22 ± 5.98 mV. A simple and high sensitive reversed phase high performance liquid chromatography (HPLC) method was developed to identify the C60 concentration in FAS (21 µg/mL). Efficiencies of drugs were examined in both pretreatment and post-treatment groups of animals to better understand how they participate in affecting AD symptoms. Seeing that previous studies have presented antithetical declarations about whether C60 is a P-glycoprotein (P-gp) substrate, we studied FAS effects in both conditions of the presence and absence of a P-gp inhibitor (verapamil HCl, 25 mg/kg). In order to clarify the molecular mechanisms of action of two drugs, their effects on the expression of three principal genes involved in AD, including Sirtuin6, SELADIN1, and AQP1, and as well as their total antioxidant capacities (TACs) were studied. In order to induce memory impairment, scopolamine HBr (SCOP) was administered for 10 days (2 mg/kg/i.p.). FAS and DNPZL administration regimens were 21 µg/mL, BID (i.p.) and 10 mg/kg (p.o.) for 10 days, respectively. Our results introduce FAS as a promising nanoformulation for improving AD symptoms, especially memory impairment, and further assert that more studies are needed to elucidate C60 and P-gp interaction type.

Preparation, Optimization, and Evaluation of Methoxy Poly(ethylene glycol)-co-Poly(ε-caprolactone) Nanoparticles Loaded by Rivastigmine for Brain Delivery.

The objective of this study was to formulate and investigate the neuropharmacokinetics and pharmacodynamics of rivastigmine (Riv) loaded methoxy poly(ethylene glycol)-co-poly(ε-caprolactone) (MPEG-PCL) nanoparticles (Riv-NPs) in rats after IV administration. The MPEG-PCL was synthesized via ring-opening polymerization of ε-caprolactone by MPEG and used to prepare Riv-NPs by the nanoprecipitation method. Response surface D-optimal design was applied to optimize Riv-NPs drug delivery system. The optimized formulation showed a particle size (PS) of 98.5 ± 2.1 nm, drug loading (DL) of 19.2 ± 1.1%, and sustained release behavior of the drug. Moreover, the optimized Riv-NPs were characterized by AFM and DSC analyses. A simple and sensitive HPLC-DAD method for bioanalysis was developed and successfully applied to the pharmacokinetic study. The neuropharmacokinetic study in rats indicated that the integration plot was linear, and the brain uptake clearance of the drug-loaded in MPEG-PCL NPs was significantly higher than the free drug. Furthermore, results of pharmacodynamic studies using the Morris water maze test demonstrated faster regain of memory loss with Riv-NPs when compared to the free drug solution. The results revealed that the mentioned biodegradable nanoparticle holds promise as a suitable drug carrier for brain drug delivery.

Preparation, optimization, and in-vitro characterization of α-tocopherol-loaded solid lipid nanoparticles (SLNs).

Objective: The main scope of present investigation was preparation and physicochemical characterization of solid lipid nanoparticles (SLNs) loaded by α-tocopherol acetate (ATA).Methods: ATA-loaded nanoparticles were prepared by solvent injection-homogenization technique using stearic acid as the solid lipid, phosphatidylcholine as the stabilizer and finally coated by chitosan with the aim of increasing z-potential and also having a more stable nano-formulation. Then, characterization of SLNs has been conducted using dynamic light scattering (DLS), zeta potential measurement, Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC).Results: Nanoparticles with average sizes of 175 ± 15 nm and zeta potential of +35 ± 2.5 mV were obtained. An excellent drug entrapment efficiency of 90.58 ± 1.38% was obtained with a no-burst slow release up to about 10 days tested. The final plateau of release of ATA from nanoparticulate system within 216 h was 61.13 ± 0.13% which was approached in about 150 h. Physical stability studies showed that the ATA nano-formulation remained stable with slight increase in mean particle size and polydispersity index over a 3-month period in refrigerated temperature. Considering both FTIR and DSC analysis, it can be concluded that there is no new band formation between materials and ATA in our nano-formulation. Particle sizes obtained using AFM images are in a good agreement to those established from the DLS analysis.Conclusion: These data showed a promising delivery system for vitamin E based on SLN platform.

Improved oral bioavailability of repaglinide, a typical BCS Class II drug, with a chitosan-coated nanoemulsion.

The aim of the present study was to develop modified nanoemulsions to improve the oral bioavailability and pharmacokinetics of a poor water-soluble drug, repaglinide (RPG). The repaglinide-loaded nanoemulsions (RPG-NEs) were prepared from olive oil as internal phase, span 80, tween 80, and poloxamer 188 as emulsifiers, using homogenization technique. The mean droplet size, zeta potential, and entrapment efficiency of RPG-NEs were 86.5 ± 3.4 nm, -33.8 ± 2.1 mV, and 96.3 ± 2.3%, respectively. The chitosan-coated RPG-NEs (Cs-RPG-NEs) showed an average droplet size of 149.3 ± 3.9 nm and a positive zeta-potential of +31.5 ± 2.8 mV. Drug release profile of RPG-NEs was significantly higher than free drug in the simulated gastrointestinal fluids (p < .005). The in vivo study revealed 3.51- and 1.78-fold increase in the AUC0-12h and Cmax of the drug, respectively, in RPG-NEs-receiving animals in comparison to the free drug. The pharmacokinetic analysis confirmed that Cs-RPG-NEs were more efficient than uncoated ones for the oral delivery of RPG. Cs-RPG-NEs showed a longer t1/2 and higher AUC0-∞ compared to control group. The relative bioavailability of Cs-RPG-NEs was higher than that of uncoated RPG-NEs and free drug. Collectively, these findings suggest that chitosan-coated nanoemulsions are promising carrier for improving the oral bioavailability of RPG.

Neuroprotective Potential of Curcumin-Loaded Nanostructured Lipid Carrier in an Animal Model of Alzheimer's Disease: Behavioral and Biochemical Evidence.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and is caused by accumulation of amyloid-ß (Aß) peptide and is associated with neurological abnormalities in learning and memory. The protective role of curcumin on nerve cells, along with a potent antioxidant and free radical scavenging activity, has been widely studied. However, its low bioavailability and limited transport ability across the blood-brain barrier are two major drawbacks of its application in the treatment of different neurodegenerative diseases. The present study was designed to improve the effectiveness of curcumin in the treatment of Aß-induced cognitive deficiencies in a rat model of AD by loading it into nanostructured lipid carriers (NLCs). The accumulation rate of curcumin (505.76±38.4 ng/g-1 h) in rat brain, as well as its serum levels, were significantly increased by using curcumin-loaded NLCs. The effective role of NLCs for brain delivery of curcumin was confirmed by reduced oxidative stress parameters (ROS formation, lipid peroxidation, and ADP/ATP ratio) in the hippocampal tissue and improvement of spatial memory. Also, histopathological studies revealed the potential of Cur-NLCs in decreasing the hallmarks of Aß in AD in the animal model. The result of studying the neuroprotective potential of Cur-NLC in both pre-treatment and treatment modes showed that loading curcumin in NLCs is an effective strategy for increasing curcumin delivery to the brain and reducing Aß-induced neurological abnormalities and memory defects and that it can be the basis for further studies in the area of AD prevention and treatment.

Oral delivery of indinavir using mPEG-PCL nanoparticles: preparation, optimization, cellular uptake, transport and pharmacokinetic evaluation.

Introduction: Indinavir (IDV) is a potent HIV protease inhibitor used in the treatment of human immunodeficiency virus (HIV). IDV is a weak base with limited aqueous solubility in its unprotonated form; therefore, solubility of IDV in the gastrointestinal tract fluids is the rate-limiting step of its absorption and onset of action. However, in many cases, drugs are not absorbed well in the gastrointestinal tract; polymer nanoparticles were recognized as an effective carrier system for drug encapsulation and are now studied as a vehicle for oral delivery of insoluble compounds. Preparation of methoxy poly (ethylene glycol)-poly (e-caprolactone) (mPEG-PCL) nanoparticles is among the strategies to overcome low bioavailability of drugs with poor aqueous solubility. Materials and method: The structure of the copolymers was characterized using 1H NMR, FTIR, DSC and GPC techniques. IDV loaded mPEG- PCL nanoparticles prepared by emulsification solvent evaporation method were optimized using D-optimal experimental design and were characterized by various techniques such as DLS, DSC, XRD, AFM and SEM. Using Caco-2 cells as a cellular model, we studied the cellular uptake and transport. Results: In vivo pharmacokinetic studies were performed in rats. The plasma AUC (0-t), t1/2 and Cmax of IDV-mPEG-PCL NPs were increased by 5.30, 5.57 and 1.37 fold compared to the IDV solution, respectively. Conclusion: The results of this study are promising for the use of biodegradable polymeric nanoparticles to improve oral drug delivery.

Magnetic brain targeting of naproxen-loaded polymeric micelles: pharmacokinetics and biodistribution study.

The blood brain barrier is a major obstacle to the entry of the majority of CNS-active agents. In the present research, the potential of magnetic polymeric micelles (MPMs) for brain-targeting of naproxen was evaluated. The MPMs were made of methoxy poly(ethyleneglycol)-poly (caprolactone) copolymer and super paramagnetic iron oxide nanoparticles (SPIONs). To investigate the impact of particle size on the in vivo biofate of nanoparticles, MPMs with two different sizes were prepared. The prepared magnetic polymeric micelles had diameters of 137 ±â€¯3.5 nm (MPM137) and 242 ±â€¯6.2 nm (MPM242) and their surface charges were about -6.5 and - 4.5 mV, respectively. Pharmacokinetic and biodistribution of nanoparticles were characterized in rats using an external magnet of 0.4 Tesla field strength located on the skull of anesthetized animals. Significant differences in volumes of central as well as peripheral compartments were observed between both MPM formulations and free naproxen solution. After 8 h of administration, the brain concentration of naproxen was shown to be higher in the case of MPM137 in comparison with MPM242 and free drug. The findings revealed that the polymeric magnetic micelles with diameters smaller than 150 nm could be initially considered as a promising carrier to improve therapeutic agent accumulation in the brain for the treatment of CNS diseases.

Mesoporous Silica-Based Materials with Bactericidal Properties.

Bacterial infections are the main cause of chronic infections and even mortality. In fact, due to extensive use of antibiotics and, then, emergence of antibiotic resistance, treatment of such infections by conventional antibiotics has become a major concern worldwide. One of the promising strategies to treat infection diseases is the use of nanomaterials. Among them, mesoporous silica materials (MSMs) have attracted burgeoning attention due to high surface area, tunable pore/particle size, and easy surface functionalization. This review discusses how one can exploit capacities of MSMs to design and fabricate multifunctional/controllable drug delivery systems (DDSs) to combat bacterial infections. At first, the emergency of bacterial and biofilm resistance toward conventional antimicrobials is described and then how nanoparticles exert their toxic effects upon pathogenic cells is discussed. Next, the main aspects of MSMs (e.g., physicochemical properties, multifunctionality, and biosafety) which one should consider in the design of MSM-based DDSs against bacterial infections are introduced. Finally, a comprehensive analysis of all the papers published dealing with the use of MSMs for delivery of antibacterial chemicals (antimicrobial agents functionalized/adsorbed on mesoporous silica (MS), MS-loaded with antimicrobial agents, gated MS-loaded with antimicrobial agents, MS with metal-based nanoparticles, and MS-loaded with metal ions) is provided.