Multiple Emulsion Solvent Evaporation Method Research Articles

Auranofin-loaded PLGA nanoparticles alleviate cognitive deficit induced by streptozotocin in rats model: modulation of oxidative stress, neuroinflammatory markers, and neurotransmitters.

Alzheimer's disease remains an unsolved neurological puzzle with no cure. Current therapies offer only symptomatic relief, hindered by limited uptake through the blood-brain barrier. Auranofin, an FDA-approved compound, exhibits potent antioxidative and anti-inflammatory properties targeting brain disorders. Yet, its oral bioavailability challenge prompts the exploration of nanoformulation-based solutions enhancing blood-brain barrier penetrability. The study aimed to investigate the neuroprotective potential of auranofin nanoparticles in streptozotocin-induced AD rats. Auranofin-containing polylactic-co-glycolic acid nanoparticles were formulated by the multiple emulsion solvent evaporation method. Characterization was done by determining entrapment efficiency, particle size distribution, surface charge, and morphology. An in vivo study was performed by administering streptozotocin (3mg/kg/i.c.v., days 1 and 3), auranofin (5 and 10mg/kg), auranofin nanoparticles (2.5 and 5mg/kg), and donepezil (2mg/kg) for 14days orally. Behavioral deficits were evaluated using the open field test, Morris water maze, objective recognition test, change in oxidative stress levels, and AD markers in the brain. Following the decapitation of the rats, the brains were excised to isolate the hippocampus. Subsequent analyses included the quantification of biochemical and neuroinflammatory markers, as well as the assessment of neurotransmitter levels. The characterization of auranofin nanoparticles showed an entrapment efficiency of 98%, an average particle size of 101.5 ± 10.3nm, a surface charge of 27.5 ± 5.10mV, and a polydispersity index of 0.438 ± 0.12. In vivo, administration of auranofin and auranofin nanoparticles significantly reversed streptozotocin-induced cognitive deficits, biochemical alteration, neuroinflammatory markers, and neurotransmitter levels. The present finding suggests that auranofin nanoparticles have more significant neuroprotective potential than auranofin alone. The therapeutic efficacy may be attributed to its antioxidant and anti-inflammatory properties, as well as its positive neuromodulatory effects. Therefore, our findings suggest that it could be a promising candidate for Alzheimer's disease therapy.

PH-responsive Astragalus polysaccharide-loaded PLGA nanoparticles as an adjuvant system to improve immune responses

Modern medical science believes that astragalus polysaccharides (APS) have the efficacy of strengthening immune system, while their peculiarities greatly reduced clinical applications. Poly(lactic-co-glycolic acid) (PLGA) is a synthetic carrier material with outstanding biochemical properties. In this study, PLGA materials were used to prepare the novel pH-responsive targeting drug delivery carriers which were encapsulated APS inside. The OVA-loaded pH-responsive APS-encapsulated PLGA Nanoparticles (OVA-loaded pH-responsive APSPs) and the OVA-loaded APSPs were constructed by multiple emulsion solvent evaporation method. Characterization and immunoenhancing activities of PLGA nanoparticles (NPs) were evaluated in vitro and in vivo. The size of NPs ranged from 142.6 to 194.6 nm, and all NPs were negatively charged. Additionally, pH-responsive APSPs shown violent release behaviors in an acidic environment. pH-responsive APSPs had low cytotoxicity, and significantly enhanced expression of MHC-II, CD80, CD86, and phagocytosis ability of macrophages. Both OVA-loaded NPs could stimulate greater Th1-biased immune responses compared with APS alone, and they could significantly promote proliferation, differentiation, and maturity of splenic lymphocytes and dendritic cells in mice respectively. NPs induced significantly greater antigen-specific IgG antibody responses and expression of IL-4, IL-6, IFN-γ, and TNF-α. Moreover, OVA-loaded pH-responsive APSPs had an aptitude for both cellular and humoral immunity reinforcement during early immunization, while OVA-loaded APSPs had advantages on later stages of immune responses.

Construction of magnetic drug delivery system and its potential application in tumor theranostics

Magnetic nanoparticles(NPs) are characterized by a rich variety of properties. Because of their excellent physical and chemical properties, they have come to the fore in biomedicine and other fields. The magnetic NPs were extensively studied in magnetic separation of cells, targeted drug delivery, tumor hyperthermia, chemo-photothermal therapy, magnetic resonance imaging (MRI) and other biomedical fields. Magnetic NPs are increasingly used in magnetic resonance imaging (MRI) based on their inherent magnetic targeting, superparamagnetic enzyme-like catalytic properties and nanoscale size. Poly(lactic-co-glycolic acid) (PLGA) is a promising biodegradable material approved by FDA and EU for drug delivery. Currently, PLGA-based magnetic nano-drug delivery systems have attracted the attention of researchers. Herein, we achieved the effective encapsulation of sized-controlled polyethylene glycol-3,4-dihydroxy benzyl-amine-coated superparamagnetic iron oxide nanoparticles (SPIO NPs) and euphorbiasteroid into PLGA nanospheres via a modified multiple emulsion solvent evaporation method (W1/O2/W2). NPs with narrow size distribution and acceptable magnetic properties were developed that are very useful for applications involving cancer therapy and MRI. Furthermore, SPIO-PLGA NPs enhanced the MRI T2 relaxation properties of tumor sites.The prepared SPIO NPs and magnetic PLGA nanospheres can be promising magnetic drug delivery systems for tumor theranostics. This study has successfully constructed a tumor-targeting and magnetic-targeting smart nanocarrier with enhanced permeability and retention, multimodal anti-cancer therapeutics and biodegradability, which could be a hopeful candidate for anti-tumor therapy in the future.

PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities.

Antimicrobial drugs face numerous challenges, including drug resistance, systemic toxic effects, and poor bioavailability. To date, treatment choices are limited, which warrants the search for novel potent antivirals, including those extracted from natural products. The seeds of Peganum harmala L. (Zygophyllaceae family) have been reported to have antimicrobial, antifungal, and anticancer activities. In the present study, a 2-hydroxy propyl-β-cyclodextrin (HPβCD)/harmala alkaloid-rich fraction (HARF) host–guest complex was prepared using a thin-film hydration method to improve the water solubility and bioavailability of HARF. The designed complex was then co-encapsulated with ascorbic acid into PLGA nanoparticles coated with polyethylene glycol (HARF–HPßCD/AA@PLGA-PEG NPs) using the W/O/W multiple emulsion-solvent evaporation method. The average particle size, PDI, and zeta potential were 207.90 ± 2.60 nm, 0.17 ± 0.01, and 31.6 ± 0.20 mV, respectively. The entrapment efficiency for HARF was 81.60 ± 1.20% and for ascorbic acid was 88 ± 2.20%. HARF–HPßCD/AA@PLGA-PEG NPs had the highest antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.025 mg/mL). They also exhibited high selective antiviral activity against the H1N1 influenza virus (IC50 2.7 μg/mL) without affecting the host (MDCK cells). In conclusion, the co-encapsulation of HPCD–HARF complex and ascorbic acid into PLGA-PEG nanoparticles significantly increased the selective H1N1 killing activity with minimum host toxic effects.

Dual targeting smart drug delivery system for multimodal synergistic combination cancer therapy with reduced cardiotoxicity

This study first reports the development of a smart drug delivery system (DDS) for multimodal synergistic cancer therapy combining chemo-photothermal-starvation approaches. A magnetic photothermal agent was synthesized by preparing iron oxide (IO) nanoparticles (NPs) with covalently attached indocyanine green (ICG) and glucose oxidase (GOx) (ICGOx@IO). Synthesized ICGOx@IO NPs were co-encapsulated with doxorubicin (Dox) and EGCG ((-)-epigallocatechin-3-gallate) inside PLGA (poly(lactic-co-glycolic acid)) NPs using multiple emulsion solvent evaporation method. Such formulation gave the advantage of triggered drug release by near-infrared (NIR) laser irradiation (808 nm at 1 W/cm2). RGD peptide was attached to the surface of PLGA NPs and the final hydrodynamic size was around 210 nm. Dual targeting by peptide and 240 mT external magnet significantly improved cellular uptake. Cellular uptake was observed using FACS, electron and optical microscopy. Dual targeting along with laser irradiation could reduce in vitro cell viability by 90 ± 2% (Dox-equivalent dose: 10 µg/ml) and complete tumor ablation was achieved in vivo due to synergetic therapeutic effect. Another attractive feature of the DDS was the significant reduction of cardiotoxicity of doxorubicin by EGCG. This new platform is thus expected to hold strong promise for future multimodal combination therapy of cancers. Statement of significanceDoxorubicin is one of the most studied and effective chemotherapeutic agents whose application is hindered due to its cardiotoxicity. In this study, we used (-)-Epigallocatechin-3-gallate (EGCG) to overcome that limitation. However, drug delivery to tumor sites with no/minimum accumulation in healthy organs is always challenging. Although peptide-based targeting is very popular, the effectiveness of receptor/ligand binding active targeting is sometimes questioned which motivated us to apply dual targeting approach. Multimodal therapies can exhibit synergistic effects and subsequently reduce the required dose of drug over monotherapy. We aimed to achieve chemo-photothermal-starvation combination therapy in this study and such achievement is yet to be reported. Our developed system also has the advantage of triggered drug release by near-infrared (NIR) laser irradiation.

Characterization and anticancer efficacy of tamoxifen citrate nanosuspension against MCF-7 breast cancer cells

Nanotechnology is one of the important fields that developed strategies to solve the issue of Tamoxifen (TAM) toxicity, owing to the capacity of nano-enabled-formulations to deliver smaller concentrations of TAM to cancer cells, over a longer period of time. Many different TAM-containing-nano systems have been successfully fabricated to selectively deliver TAM to particular molecular targets on tumour membranes, decreasing unwanted toxic effects. The present study was carried out to synthesis the tamoxifen citrate nanosuspension and also to find its effectiveness against breast cancer cells. Nanoparticles were made using multiple emulsion solvent evaporation method and its characterizations were studied. The structure and morphological examination of tamoxifen citrate Liquid self-nanoemulsifying drug delivery systems were observed with transmission electron microscopy. The cytotoxic effect of tamoxifen citrate L-SNEDDS against breast cancer MCF-7 cells was measured by cell viability assay. The cytotoxic effect of tamoxifen citrate L-SNEDDS enhanced significantly as the concentration of drug enhanced from 25 μM to 250 μM. The toxic action of tamoxifen citrate L-SNEDDS on cancer cells remarkably reduced cell viability from 100% to 20.3%, while nanosuspension devoid of the drug presented cell viability of 99.5%. A significant decrease in cell viability was found in tamoxifen citrate free drug from 100% to 30.9%. In conclusion, tamoxifen citrate Liquid self-nanoemulsifying drug delivery systems showed cytotoxic activity on MCF-7 breast cancer cell lines.

Preparation of PLGA microspheres loaded with 10-hydroxycamptothecin and arsenic trioxide and their treatment for rabbit hepatocellular carcinoma.

This study aims to study the preparation method of arsenic trioxide (As2O3) polylactic-co-glyconlic acid (PLGA) microspheres and 10-hydroxycamptothecin (HCPT) PLGA microspheres and explore their therapeutic effects as embolic agents for VX2 hepatocellular carcinoma in rabbits. As2O3 and HCPT PLGA microspheres were prepared by multiple emulsion solvent evaporation method. Scanning electron microscopy (SEM) and particle size distribution were used to analyze the morphology, the drug sustained release ability was observed by the release of microspheres in vitro. The rabbit model of VX2 hepatocellular carcinoma was established and the hepatocellular carcinoma was treated with combined microspheres. The therapeutic effects were detected by qPCR, western blotting, HE staining and immunohistochemical methods. The PLGA microspheres loaded with As2O3 and HCPT were successfully prepared by optimizing the ratio. The particle size was between 30 and 50 μm. In vitro release results showed that PLGA microspheres loaded with As2O3 released completely in 10 days and PLGA microspheres loaded with HCPT released completely in 12 days. Western blotting and qPCR results showed that the expression of ALDH1A1 and Nanog decreased significantly in treatment group. HE staining and immunohistochemical analysis showed that the expression of CD31, HIF and VEGF decreased significantly and the apoptosis of tissues was obvious. The combination of As2O3 and HCPT PLGA microspheres as embolization for VX2 hepatocellular carcinoma in rabbits has significant therapeutic effect.

Controlled Release and Photothermal Behavior of Multipurpose Nanocomposite Particles Containing Encapsulated Gold-Decorated Magnetite and 5-FU in Poly(lactide-co-glycolide).

Nowadays, many research studies have been conducted to prepare multidisciplinary probes in drug delivery systems and cancer therapy with high performance and minimum side effects. Here, poly(lactide-co-glycolide) (PLGA) nanocomposite particles containing 5-fluorouracil (5-FU) and gold-decorated magnetite nanoparticles with a raspberry-like morphology were designed and prepared as a novel and anticancer probe. For this reason, Fe3O4 nanoparticles were synthesized by a coprecipitation method and modified with (3-mercaptopropyl) trimethoxysilane for the deposition of gold nanoparticles. Then, they were embedded in the PLGA matrix alone and accompanied by 5-FU with 92 and 88% loading efficiencies, respectively, through a multiple emulsion solvent evaporation method. Chemical structure and composition of the prepared samples in each step were completely characterized by several techniques. The morphology of the nanocomposite particles was assessed by field emission scanning electron microscopy, high-resolution transmission electron microscopy, and selected area electron diffraction patterns, and their particle size and colloidal stability after 1 week were evaluated by dynamic light scattering. Because of the coexistence of gold and Fe3O4 nanoparticles, the final probe provided enhanced dual magneto and photothermal responses by increasing the temperature up to 42.7 °C under 5 min external alternating magnetic field and to 42.1 °C within just 1 min near-infrared irradiation at 808 nm. Trypan blue dye exclusion assays showed that they are biocompatible with reasonable toxicity (IC50 of 0.62 mg/mL) with respect to DU145 prostate cancer cells. Drug release profile of the 5-FU-loaded nanocomposite particles demonstrated their controlled release at 37 °C in phosphate-buffered saline solution. These indicate multidisciplinary characteristics of such particles in cancer therapy by photothermal, magnetic hyperthermia, and chemotherapy according to the presence of various active components.

Recent Advance in Polymer Based Microspheric Systems for Controlled Protein and Peptide Delivery.

Sustained-release systems made by biodegradable polymers for protein and peptide drug delivery have received considerable attention by academic researchers and major pharmaceutical companies around the world. Various types of biodegradable materials, including natural and synthetic polymers, have been applied to form protein and peptide drug carriers. Among these material candidates, poly lactic acid (PLA) and poly lactic-co-glycolic acid (PLGA) are the most commonly used biodegradable materials in the development of protein and peptide microspheres. In addition, many microsphere preparation technologies, including spray drying, coacervation, multiple emulsion solvent evaporation method and microporous membrane emulsification have been developed for microspheres preparation. In this review, we particularly summarize and briefly introduce the materials and methods that are used to fabricate microspheres as protein delivery systems. The existing opportunities and challenges for successful protein delivery are also discussed.

Ketoprofen and MicroRNA-124 Co-loaded poly (lactic-co-glycolic acid) microspheres inhibit progression of Adjuvant-induced arthritis in rats

Ketoprofen, a non-steroid anti-inflammatory drug, is widely used for relieving the pain and swelling caused by rheumatoid arthritis. However, ketoprofen can’t suppress disease progression effectively. In this study, in an effort to improve the therapeutic effect for rheumatoid arthritis (RA), microRNA-124 (miR-124), a promising new therapeutic agent for RA, was co-loaded with ketoprofen into poly (lactic-co-glycolic acid) (PLGA) microspheres and administrated to adjuvant-induced arthritis rats. PLGA microspheres loaded with ketoprofen and miR-124 were prepared by a modified multiple emulsion–solvent evaporation method. In vivo pharmacodynamics experimental results indicated ketoprofen in co-loaded microspheres could significantly reduce inflammation of the joints and miR-124 in the microspheres could reduce bone damage. In addition, ketoprofen and miR-124 co-loaded PLGA microspheres had a remarkable advanced activity over delivery of either miR-124 or ketoprofen in suppressing adjuvant-induced arthritis (AA) in rats. Results of western blot and immunohistochemistry revealed that miR-124 could reduce the level of receptor activator of nuclear factor kappa-B ligand (RANKL). These results suggested co-delivery of ketoprofen and miR-124 could achieve synergistic effects on preventing inflammation and bone damage caused by AA. Ketoprofen and miR-124 co-loaded PLGA microspheres could be a promising combined therapeutic strategy against RA.

In vivo evaluation of the combination effect of near-infrared laser and 5-fluorouracil-loaded PLGA-coated magnetite nanographene oxide

Magnetite nanographene oxide has exhibited great potential in drug delivery and photothermal therapy (PTT) for cancer treatment. Here we developed 5-fluorouracil-loaded poly (lactic-co-glycolic acid)-coated magnetite nanographene oxide (NGO-SPION-PLGA-5-Fu) to simplify combined PTT and chemotherapy in one complex. The nanocarrier was synthesized using a modified O1/W1/O2/W2 multiple emulsion solvent evaporation method and was characterized for size, zeta potential, drug loading, in vitro and in vivo release. In this paper, in vivo suppression effect of PTT and chemotherapy using this synthesized magnetite nanographene oxide was studied. The in vitro release of 5-Fu from nanoparticles showed that 41.36% of the drug was released within 24 h. In vivo release showed that 5-Fu has a sustained release profile and prolonged lifetime in the rabbit plasma. Remarkably, a single injection of NGO-SPION-PLGA-5-Fu and 808 nm near-infrared laser (NIR) irradiation for 3 min effectively suppressed the growth of tumours compared with 5-Fu alone (p < .01). Magnetic resonance imaging (MRI) confirmed that the magnetic nanographene oxide was effectively targeted to the tumour site. Therefore, NGO-SPION-PLGA-5-Fu showed excellent PTT efficacy, magnetic targeting property, and MRI ability, indicating that there is a great potential of NGO-SPION-PLGA-5-Fu for cancer theranostic applications.

Preparation of Porous Polylactide Microspheres and Their Application in Tissue Engineering

In this study, porous polylactide (PLA) microspheres with different structures were prepared through the multiple emulsion solvent evaporation method. By changing organic solvents (ethyl acetate and chloroform) and adding effervescent salt NH4HCO3 in the inner water phase, microspheres with porous capsular, matrix, microcapsular and multivesicular structures were prepared. The protein encapsulation and release, and the cell growth behavior of porous microspheres were further explored. Under the same inner water phase, microspheres prepared with chloroform had higher protein encapsulation efficiency and less protein release rate as compared with those prepared with ethyl acetate. Cell experiments showed that the relatively rough surface of microspheres prepared with chloroform was more favorable for the cell growth in comparison with the smooth surface of microspheres prepared with ethyl acetate. This study shows a simple and effective method to control the protein release and cell growth behaviors of polymer microspheres by tuning their porous structure.

In vitro and in vivo evaluation of anti-nucleolin-targeted magnetic PLGA nanoparticles loaded with doxorubicin as a theranostic agent for enhanced targeted cancer imaging and therapy

A superparamagnetic iron oxide nanoparticles (SPIONs)/doxorubicin (Dox) co-loaded poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeted with AS1411 aptamer (Apt) against murine C26 colon carcinoma cells is successfully developed via a modified multiple emulsion solvent evaporation method for theranostic purposes. The mean size of SPIO/Dox-NPs (NPs) was 130nm with a narrow particle size distribution and Dox loading of 3.0%. The SPIO loading of 16.0% and acceptable magnetic properties are obtained and analyzed using thermogravimetric and vibration simple magnetometer analysis, respectively. The best release profile from NPs was observed in PBS at pH 7.4, in which very low burst release was observed. Nucleolin is a targeting ligand to facilitate anti-tumor delivery of AS1411-targeted NPs. The Apt conjugation to NPs (Apt-NPs) enhanced cellular uptake of Dox in C26 cancer cells. Apt-NPs enhance the cytotoxicity effect of Dox followed by a significantly higher tumor inhibition and prolonged animal survival in mice bearing C26 colon carcinoma xenografts. Furthermore, Apt-NPs enhance the contrast of magnetic resonance images in tumor site. Altogether, these Apt-NPs could be considered as a powerful tumor-targeted delivery system for their potential as dual therapeutic and diagnostic applications in cancers.

Preparation and characterization of uniform-sized PLGA nanospheres encapsulated with oleic acid-coated magnetic-Fe3O4 nanoparticles for simultaneous diagnostic and therapeutic applications

In recent years, magnetic nanoparticles are increasingly studied and exploited for their potential applications as magnetic resonance imaging (MRI11Magnetic resonance imaging) contrast agents, cancer treatment, targeted therapy, delivery vectors and hyperthermia. Todays, magnetic systems based on polymeric materials such as poly(lactic-co-glycolic acid) (PLGA22Poly(lactic-co-glycolic acid)) have been of special interest for their biomedical applications. In this study, we achieved an effective method for encapsulation of sized-controlled oleic acid-coated superparamagnetic iron oxide (SPIO33Superparamagnetic iron oxide NPs44Nanoparticles) into the PLGA nanospheres via a modified multiple emulsion solvent evaporation method (O1/W1/O2/W255Oil-in-water-in- oil-in-water) resulted in development of the NPs with narrow size distribution and acceptable magnetic properties that are very vital and curtail at targeting and magnetic properties of NPs for both anti-cancer therapy and magnetic resonance imaging studies. The SPIO NPs and SPIO-PLGA nanospheres showed spherical morphology with narrow size distribution of 10nm and 130nm, respectively. SPIO-PLGA nanospheres with high SPIO loading of 18.0% and magnetic properties of 5.9 emu/g were obtained. Furthermore, SPIO-PLGA NPs enhance the contrast of relaxation time (T166Relaxation time)-weighted imaging in tumor site. The prepared SPIO NPs and magnetic PLGA nanosphere could be promising superparamagnetic nanoparticles for simultaneous diagnostic and therapeutic applications.

Study and evaluation of nucleolin-targeted delivery of magnetic PLGA-PEG nanospheres loaded with doxorubicin to C6 glioma cells compared with low nucleolin-expressing L929 cells

Magnetic nanoparticulate systems based on polymeric materials such as poly (lactic-co-glycolic acid) (PLGA11Poly (lactic-co-glycolic acid).) are being studied for their potential applications in targeted therapy and imaging of malignant tumors. In the current study, superparamagnetic iron oxide nanocrystals (SPIONs22Superparamagnetic iron oxide nanocrystals.) and doxorubicin (Dox33Doxorubicin.) were entrapped in the PLGA-based nanoparticles via a modified multiple emulsion solvent evaporation method. Furthermore, SPIO/Dox-NPs44Nanoparticles. were conjugated to anti-nucleolin AS1411 aptamer (Apt55Aptamer.) and their targeting ability was investigated in high nucleolin-expressing C6 glioma cells compared to low nucleolin-expressing L929 cells. The NPs exhibited a narrow size distribution with mean diameter of ~170nm and an appropriate SPION content (~18% of total polymer weight) with a sufficient saturation magnetization value of 5.9emu/g which is suitable for imaging objectives. They manifested an increased Dox release at pH5.5 compared to pH7.4, with initial burst release (within 24h) followed by sustained release of Dox for 36days. The Apt conjugation to NPs enhanced cellular uptake of Dox in C6 glioma cells compared to L929 cells. Similarly, the Apt-NPs increased the cytotoxicity effect of Dox compared with NPs and Dox solution (f-Dox) alone. In conclusion, the Apt-NPs were found to be a promising delivery system for therapeutic and diagnostic purposes.

A new method of wound treatment: targeted therapy of skin wounds with reactive oxygen species-responsive nanoparticles containing SDF-1α.

ObjectiveTo accelerate wound healing through promoting vascularization by using reactive oxygen species (ROS)-responsive nanoparticles loaded with stromal cell-derived factor-1α(SDF-1α).MethodsThe ROS-reactive nanomaterial poly-(1,4-phenyleneacetone dimethylene thioketal) was synthesized, and its physical and chemical properties were characterized. ROS-responsive nanoparticles containing SDF-1α were prepared through a multiple emulsion solvent evaporation method. The loading capacity, stability, activity of the encapsulated protein, toxicity, and in vivo distribution of these nanoparticles were determined. These nanoparticles were administered by intravenous infusion to mice with full-thickness skin defects to study their effects on the directed chemotaxis of bone marrow mesenchymal stem cells, wound vascularization, and wound healing.ResultsThe synthesized ROS-reactive organic polymer poly-(1,4-phenyleneacetone dimethylene thioketal) possessed a molecular weight of approximately 11.5 kDa with a dispersity of 1.97. ROS-responsive nanoparticles containing SDF-1α were prepared with an average diameter of 110 nm and a drug loading capacity of 1.8%. The encapsulation process showed minimal effects on the activity of SDF-1α, and it could be effectively released from the nanoparticles in the presence of ROS. Encapsulated SDF-1α could exist for a long time in blood. In mice with full-thickness skin defects, SDF-1α was effectively released and targeted to the wounds, thus promoting the chemotaxis of bone marrow mesenchymal stem cells toward the wound and its periphery, inducing wound vascularization, and accelerating wound healing.

Preparation and characterization of Tamoxifen citrate loaded nanoparticles for breast cancer therapy.

BackgroundFour formulations of Tamoxifen citrate loaded polylactide-co-glycolide (PLGA) based nanoparticles (TNPs) were developed and characterized. Their internalization by Michigan Cancer Foundation-7 (MCF-7) breast cancer cells was also investigated.MethodsNanoparticles were prepared by a multiple emulsion solvent evaporation method. Then the following studies were carried out: drug-excipients interaction using Fourier transform infrared spectroscopy (FTIR), surface morphology by field emission scanning electron microscopy (FESEM), zeta potential and size distribution using a Zetasizer Nano ZS90 and particle size analyzer, and in vitro drug release. In vitro cellular uptake of nanoparticles was assessed by confocal microscopy and their cell viability (%) was studied.ResultsNo chemical interaction was observed between the drug and the selected excipients. TNPs had a smooth surface, and a nanosize range (250–380 nm) with a negative surface charge. Drug loadings of the prepared particles were 1.5%±0.02% weight/weight (w/w), 2.68%±0.5% w/w, 4.09%±0.2% w/w, 27.16%±2.08% w/w for NP1–NP4, respectively. A sustained drug release pattern from the nanoparticles was observed for the entire period of study, ie, up to 60 days. Further, nanoparticles were internalized well by the MCF-7 breast cancer cells on a concentration dependent manner and were present in the cytoplasm. The nucleus was free from nanoparticle entry. Drug loaded nanoparticles were found to be more cytotoxic than the free drug.ConclusionTNPs (NP4) showed the highest drug loading, released the drug in a sustained manner for a prolonged period of time and were taken up well by the MCF-7 breast cancer cell line in vitro. Thus the formulation may be suitable for breast cancer treatment due to the good permeation of the formulation into the breast cancer cells.

PLGA microspheres encapsulating siRNA anti-TNFalpha: Efficient RNAi-mediated treatment of arthritic joints

The aim of this study was to investigate potentialities of poly(dl-lactide–co-glycolide) (PLGA) microspheres for the delivery of small interfering RNAs (siRNAs) against tumor necrosis factor α (TNF-α) to achieve prolonged and efficient inhibition of TNF-α for the treatment of rheumatoid arthritis (RA). PLGA microspheres were prepared by a modified multiple emulsion–solvent evaporation method. The formulations were characterized in terms of morphology, mean diameter and siRNAs distribution, encapsulation efficiency, and in vitro release kinetics. The efficiency of this system was then evaluated both in vitro and in vivo using the murine monocytic cell line J774 and a pre-clinical model of RA, respectively. siRNA-encapsulating PLGA microspheres were characterized by a high encapsulation efficiency and a slow and prolonged anti-TNF-α siRNAs. Our results provide evidence that, upon intra-articular administration, PLGA microspheres slowly releasing siRNAs effectively inhibited the expression of TNF-α in arthritic joints. Our system might represent an alternative strategy for the design of novel anti-rheumatic therapies based on the use of RNA interference in RA.

Novel preparation of PLGA/HP55 nanoparticles for oral insulin delivery

The aim of the present study was to develop the PLGA/HP55 nanoparticles with improved hypoglycemic effect for oral insulin delivery. The insulin-loaded PLGA/HP55 nanoparticles were produced by a modified multiple emulsion solvent evaporation method. The physicochemical characteristics, in vitro release of insulin, and in vivo efficacy in diabetic rats of the nanoparticles were evaluated. The insulin encapsulation efficiency was up to 94%, and insulin was released in a pH-dependent manner under simulated gastrointestinal conditions. When administered orally (50 IU/kg) to diabetic rats, the nanoparticles can decrease rapidly the blood glucose level with a maximal effect between 1 and 8 h. The relative bioavailability compared with subcutaneous injection (5 IU/kg) in diabetic rats was 11.3% ± 1.05%. This effect may be explained by the fast release of insulin in the upper intestine, where it is better absorbed by the high gradient concentration of insulin than other regions. These results show that the PLGA/HP55 nanoparticles developed in the study might be employed as a potential method for oral insulin delivery.

A multiple emulsion method for loading 5-fluorouracil into a magnetite-loaded nanocapsule: a physicochemical investigation

The preparation of 5-fluorouracil (5-FU) loaded poly(lactic-co-glycolic acid) (PLGA) biodegradable nanocapsules containing magnetite nanoparticles was studied through the modified multiple emulsion solvent evaporation method for magnetically controlled delivery of anticancer drugs. The morphology and size distribution of the prepared magnetite/PLGA nanocapsules were investigated by transmission and scanning electron microscopy. The micrographs showed that the magnetic nanocapsules were almost spherical in shape and their mean diameter was in the nanometer range with a narrow size distribution. Fourier transform infrared and ultraviolet–visible spectroscopy confirmed incorporation of 5-FU molecules into the PLGA matrix. The magnetite content was assessed by thermogravimetric and magnetometry analysis and the results showed a magnetite content of 35 wt% with high magnetic responsivity. Magnetometry measurements showed superparamagnetic properties of the magnetic nanocapsules with a saturation magnetization of 13.7 emu g−1. Such biodegradable magnetic nanocapsules could be considered as an appropriate choice for drug targeting. Furthermore, the influence of some important processing parameters such as PLGA concentration, initial loading of 5-FU and poly(vinyl alcohol) concentration on drug content, encapsulation efficiency and in vitro drug release kinetics was investigated and optimized. The drug content and encapsulation efficiency of the magnetic nanocapsules were 4–7 wt% and 60%–80%, respectively, and the nanocapsules demonstrated controlled release of 5-FU at 37 °C in a buffer solution. All samples exhibited a burst release at the initial stage and this burst release showed its close dependence on the formulation parameters. Copyright © 2012 Society of Chemical Industry