Nanoparticulate Delivery Systems Research Articles

Nanoparticles for vaccine and gene therapy: Overcoming the barriers to nucleic acid delivery.

Nucleic acid therapeutics can be used to control virtually every aspect of cell behavior and therefore have significant potential to treat genetic disorders, infectious diseases, and cancer. However, while clinically approved to treat a small number of diseases, the full potential of nucleic acid therapeutics is hampered by inefficient delivery. Nucleic acids are large, highly charged biomolecules that are sensitive to degradation and so the approaches to deliver these molecules differ significantly from traditional small molecule drugs. Current studies suggest less than 1% of the injected nucleic acid dose is delivered to the target cell in an active form. This inefficient delivery increases costs and limits their use to applications where a small amount of nucleic acid is sufficient. In this review, we focus on two of the major barriers to efficient nucleic acid delivery: (1) delivery to the target cell and (2) transport to the subcellular compartment where the nucleic acids are therapeutically active. We explore how nanoparticles can be modified with targeting ligands to increase accumulation in specific cells, and how the composition of the nanoparticle can be engineered to manipulate or disrupt cellular membranes and facilitate delivery to the optimal subcellular compartments. Finally, we highlight how with intelligent material design, nanoparticle delivery systems have been developed to deliver nucleic acids that silence aberrant genes, correct genetic mutations, and act as both therapeutic and prophylactic vaccines. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

Environment friendly green synthesis method based natural bioactive functional “catechin and gingerol” loaded nanomedicine for the management of obesity

Obesity is one of the major health problems across the world and the leading cause of death. Natural bioactive functional compounds (catechin, Cat and gingerol, Gin) have been reported to control obesity. The application of a nanoparticulate (NPs) delivery system has shown greater efficacy in the treatment of different diseases. The present study was designed to prepare the Cat-Gin silver nanoparticles (AgNPs) using the microwave method. The prepared Cat-Gin-AgNPs were characterized for particle size, zeta potential, encapsulation efficiency and drug release. Further, it was evaluated for anti-obesity activity (body weight, total abdominal fat, lipid profile and liver profile) using a high-fed diet (HFD) induced obesity model. The formulated Cat-Gin-AGNPs showed nano-metric size (110 ± 4.65 nm), polydispersity index (PDI) of 0.27 ± 0.03, and surface charge (−17.6 ± 2.6 mV) with a spherical shape. It also depicted high encapsulation efficiency (<80 %) with prolonged drug release behaviour (Cat – 84.34 ± 4.12 % and Gin – 72.33 ± 3.87 %). The in vivo study parameters revealed a significant (p ≤ 0.001) reduction in body weight, food intake and total abdominal fat. The biochemical results displayed a reversal in altered biochemical parameters to the normal range (Group 4) as compared to HFD control (Group 2). It also helps restored the liver enzymes in obese rats. The results of the study highlighted the applicability of Cat-Gin-AGNPs as a novel delivery system in the treatment of obesity.

Quaternized chitosan-coated liposomes enhance immune responses by co-delivery of antigens and resveratrol

Co-localization of antigens and immunomodulators in the same antigen-presenting cells (APCs) can powerfully activate APCs and enhance immune responses. In this study, the immunomodulator resveratrol (Res) was encapsulated into quaternized chitosan (QCS) - coated liposomes for developing a new nanoparticle delivery system (QCS-Res-LP), and ovalbumin (OVA) was selected as a model antigen and adsorbed on the surface of QCS-Res-LP. The results showed that the particle size of QCS-Res-LP was 96.3 ± 3.52 nm; the PDI value was 0.280 ± 0.010; the Zeta potential was 9.59 ± 0.36 mV. QCS-Res-LP could encapsulate 76.22 ± 1.02 % resveratrol and adsorb 88.2 ± 16.3 % antigen. QCS-Res-LP effectively promoted the co-uptake of antigen and Res by dendritic cells (DCs) with 50-fold greater than resveratrol liposomes (Res-LP). QCS-Res-LP promoted expression levels of CD80, CD86, IL-2, and IL-12 in DCs. QCS-Res-LP did not cause hemolysis. The levels of ovalbumin-specific IgG antibodies and cytokines were significantly increased in mice vaccinated with ovalbumin-absorbed QCS-Res-LP, which induced a mixed Th1/Th2 immune response. In conclusion, these results demonstrated that QCS-coated liposomes enable the co-delivery of antigens and immunomodulators to induce strong and durable immune responses.

Chitosan based micro and nano-particulate delivery systems for bacterial prodigiosin: Optimization and toxicity in animal model system

Prodigiosin, a red bacterial pigment is a compound with promising therapeutic properties. Major hindrance in applying prodigiosin in pharmaceutics is the insolubility in water and lack of bioavailability. This study aims to optimize two different types of chitosan based delivery systems, microspheres and nanoparticles for prodigiosin derived from Serratia marcescens NITDPER1 through Taguchi method and determine toxicity perspectives. The results revealed 0.5 % chitosan, 1 % sodium-alginate and 5 % CaCl2 optimum for microsphere and 0.1 % chitosan, 1.5 % TPP and 1.5 % acetic acid for nanoparticle with the entrapment efficiency and maximum release of 89.27 ± 1.2 % and 87.42 ± 1.9 % for microspheres and 96.36 ± 1.7 % and 91.58 ± 2.1 % for nanoparticles. Particle size was 93.03 ± 0.3 μm and 75.1 ± 1.4 nm for micro and nanoformulations. Kinetic parameters of release fitted best with Korsmeyer-Peppas model. Swelling index of microsphere and nanoparticles in pH 6.8 was 799 ± 7.1 % and 35.3 ± 2.1 % respectively. FESEM, FT-IR and XRD revealed spherical morphology, preservation of prodigiosin functional groups and amorphous nature of the formulations. Anticancer IC50 values were (μg mL−1) 11.7 ± 1.2, 10.8 ± 1.4 and 9.4 ± 0.8 for free prodigiosin, microsphere and nanoparticles respectively. Toxicity studies on HEK-293 cell line, Daphnia magna and zebrafish model determined non-toxic nature of the bacterial prodigiosin and its formulations revealing suitability of animal system application.

Lipid-polymer nanocarrier platform enables X-ray induced photodynamic therapy against human colorectal cancer cells

In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU) and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells’ growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

An Overview of Herbal-Based Antidiabetic Drug Delivery Systems: Focus on Lipid- and Inorganic-Based Nanoformulations.

Diabetes is a metabolic pathology with chronic high blood glucose levels that occurs when the pancreas does not produce enough insulin or the body does not properly use the insulin it produces. Diabetes management is a puzzle and focuses on a healthy lifestyle, physical exercise, and medication. Thus far, the condition remains incurable; management just helps to control it. Its medical treatment is expensive and is to be followed for the long term, which is why people, especially from low-income countries, resort to herbal medicines. However, many active compounds isolated from plants (phytocompounds) are poorly bioavailable due to their low solubility, low permeability, or rapid elimination. To overcome these impediments and to alleviate the cost burden on disadvantaged populations, plant nanomedicines are being studied. Nanoparticulate formulations containing antidiabetic plant extracts or phytocompounds have shown promising results. We herein aimed to provide an overview of the use of lipid- and inorganic-based nanoparticulate delivery systems with plant extracts or phytocompounds for the treatment of diabetes while highlighting their advantages and limitations for clinical application. The findings from the reviewed works showed that these nanoparticulate formulations resulted in high antidiabetic activity at low doses compared to the corresponding plant extracts or phytocompounds alone. Moreover, it was shown that nanoparticulate systems address the poor bioavailability of herbal medicines, but the lack of enough preclinical and clinical pharmacokinetic and/or pharmacodynamic trials still delays their use in diabetic patients.

Aptamer-functionalized chitosan-coated gold nanoparticle complex as a suitable targeted drug carrier for improved breast cancer treatment

AbstractIn the following research, we specifically assessed the feasibility of a novel AS-1411-chitosan (CS)-gold nanoparticle (AuNPs) delivery system to carry methotrexate (MTX) into the cancer cells. The designed system had a spherical shape with average size of 62 ± 2.4 nm, the zeta potential of −32.1 ± 1.4 mV, and released MTX in a controlled pH- and time-dependent manner. CS-AuNPs could successfully penetrate the breast cancer cells and release the therapeutic drug, and ultimately, be accumulated by the nucleolin-AS1411 targeting mechanism within thein vivoenvironment. The anticancer activity of MTX was attributed to the induction of mitochondria membrane potential loss and nuclear fragmentation, which leads to apoptotic death. Moreover, the cellular internalization confirmed the high potential in the elimination of cancer cells without notable cytotoxicity on non-target cells. Therefore, it was concluded that the AS1411-CS-AuNPs with considerablein vitroandin vivoresults could be utilized as a favorable system for breast cancer treatment.

Cytotoxicity and antiproliferative activity of ethanol and ethyl acetate fractions from polymeric nanoparticles of green tea leaves (Camellia sinensis) in breast cancer cell line MDA-MB-132.

Green tea (Camellia sinensis) has benefits. Its main potential content is epigallocatechin gallate, which has many bioactivity and pharmacological properties. However, herbal medicines have limitations on low solubility and stability. A nanoparticle delivery system is a perfect form of active ingredient development, because it can mediate the increase in solubility, dissolution rate, and strength of a targeted delivery system. This study aimed to make and test the formulation of the ethanol and ethyl acetate fraction from green tea leaves in the form of a nanoparticle delivery system using chitosan biopolymer as the primary carrier polymer combined with sodium tripolyphosphate as a crosslinker and then carried out the tests on the MDA-MB-231 breast cancer cell line. The results showed that the particle size value was 199.7 nm, the zeta potential was-56.7 mV, and the polydispersity index was 0.337. X-ray diffraction and differential scanning calorimetry test results showed that the C. sinensis fraction was perfectly dispersed molecularly in the nanoparticle system. The results of the cytotoxic test on the MDA-MB-231 breast cancer cell line obtained IC50 values for both fractions, namely 10.70 μg/mL (nano ethanol fraction) and 12.72 μg/mL (nano ethyl acetate fraction). This result showed a significant increase in anticancer activity in both fractions compared to those not formulated (P < 0.05). These results also show that the C. sinensis tea fraction formulated in a nanoparticle delivery system has a great potential as a new therapeutic agent for breast cancer.

Cefazolin/BMP-2-Loaded Mesoporous Silica Nanoparticles for the Repair of Open Fractures with Bone Defects.

The study aimed to explore the feasibility of a nanodrug delivery system to treat open fractures with bone defects. We developed a cefazolin (Cef)/bone morphogenetic protein 2 (BMP-2)@mesoporous silica nanoparticle (MSN) delivery system; meanwhile, Cef/MBP-2@ poly(lactic-co-glycolic acid) (PLGA) was also developed as control. For the purpose of determining the osteogenic and anti-inflammatory actions of the nanodelivery system, we cultured bone marrow mesenchymal stem cells (BMSCs) and constructed a bone defect mouse model to evaluate its clinical efficacy. After physicochemical property testing, we determined that MSN had good stability and did not easily accumulate or precipitate and it could effectively prolong the Cef's half-life by nearly eight times. In BMSCs, we found that compared with the PLGA delivery system, MSNs better penetrated into the bone tissue, thus effectively increasing BMSCs' proliferation and migration ability to facilitate bone defect repair. Furthermore, the MSN delivery system could improve BMSCs' mineralization indexes (alkaline phosphatase [ALP], osteocalcin [OCN], and collagen I [Col I]) to effectively improve its osteogenic ability. Moreover, the MSN delivery system could inhibit inflammation in bone defect mice, which was mainly reflected in its ability to reduce the release of IL-1β and IL-4 and increase IL-10 levels; it could also effectively reduce apoptosis of CD4+ and CD8+ T cells, thus improving their immune function. Furthermore, the percentage of new bones, bone mineral density, trabecular volume, and trabecular numbers in the fracture region were improved in mice treated with MSN, which allowed better repair of bone defects. Hence, Cef/BMP-2@MSN may be feasible for open fractures with bone defects.

Developing the solid lipid nanoparticles of Losartan using the stearic acid and glyceryl monostearate as the carrier matrices

This research work deals with the design and development of the solid lipid nanoparticles of Losartan to improve solubility of poorly soluble drug. Losartan solid lipid nanoparticles are formed using hot homogenization technique followed by ultrasonication technique. Experiment trend is predicted using the standard calibration curve. The parameters studied are the percent drug release, entrapment efficiency, particle size of SLN and the in-vitro drug release of prepared SLN. The results obtained in this research work clearly indicated that the developed solid lipid nanoparticle delivery system for the highly lipophilic drug, Losartan using stearic acid, glyceryl monostearate as carrier matrices can be used effectively for hypertension.

A new core-shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma.

Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for anti-HCC drugs with better targeting ability are needed. Here, we created paclitaxel (PTX)/norcantharidin (NCTD)-loaded core–shell lipid nanoparticles modified with a tumor neovasculature-targeted peptide (Ala-Pro-Arg-Pro-Gly, APRPG) and investigated their anti-tumor effects in HCC. Core–shell-type lipid nanoparticles (PTX/NCTD-APRPG-NPs) were established by combining poly(lactic-co-glycolic acid) (PLGA)-wrapped PTX with phospholipid-wrapped NCTD, followed by modification with APRPG. For comparison, PTX-loaded PLGA nanoparticles (PTX-NPs) and PTX/NCTD-loaded core–shell-type nanoparticles without APRPG (PTX/NCTD-NPs) were prepared. The in vitro and in vivo anti-tumor effects were examined in HepG2 cells and tumor-bearing mice, respectively. Morphological and release characterization showed that PTX/NCTD-APRPG-NPs were prepared successfully and achieved up to 90% release of PTX in a sustained manner. Compared with PTX/NCTD-NPs, PTX/NCTD-APRPG-NPs significantly enhanced the uptake of PTX. Notably, the inhibition of proliferation and migration of hepatoma cells was significantly higher in the PTX/NCTD-APRPG-NP group than those in the PTX-NP and PTX/NCTD-NP groups, which reflected significantly greater anti-tumor properties as well. Furthermore, key molecules in cell proliferation and apoptosis signaling pathways were altered most in the PTX/NCTD-APRPG-NP group, compared with the PTX-NP and PTX/NCTD-NP groups. Collectively, PTX/NCTD-loaded core–shell lipid nanoparticles modified with APRPG enhance the effectiveness of anti-HCC drugs and may be an effective system for the delivery of anti-HCC drugs.

Propitious maneuvering for delivery of the phytopharmaceutical “apocynin” to induced fulminant hepatitis in BALB/c mice: In vitro and in vivo assessments

Apocynin (APO), a specific nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase, NOX) inhibitor, has recently emerged as a bioactive phytochemical with eminent anti-inflammatory and anti-oxidant activities. To our knowledge, no research has been conducted to fabricate a mucoadhesive nanostructured delivery system of APO that targets the liver. Accordingly, chitosan (CS) surface decorated polymeric nanoparticulate delivery system (PNDS) was victoriously fabricated by double emulsion-solvent evaporation method. Herein, a randomized full 33 factorial design was employed to assess the impact of the independently processing parameters (IPPs) namely; (poly(d,l-lactide-co-glycolide) (PLGA) amount (A)), (polyvinyl alcohol (PVA) concentration (B)), and (CS concentration (C)), on different dependently measured attributes (DMAs). The optimal APO-loaded chitosan-coated poly(d,l-lactide-co-glycolide) nanoparticles (APO-loaded CS-coated PLGA NPs) formula (F19) would be extensively appraised through meticulous in vitro-in vivo studies. Crucially, the results revealed that oral pre-treatment with the optimal formula evoked a prodigious in vivo hepatoprotective efficacy against lipopolysaccharide (LPS)/D-(+)-galactosamine (D-GalN) induced fulminant hepatitis (FH) in BALB/c mice when compared with pure APO, uncoated F19, and plain NPs (P NPs) pretreated groups. In conclusion, APO-loaded CS-coated PLGA NPs could be considered as a promising oral mucoadhesive phytopharmaceutical PNDS to open new prospects for therapeutic intervention in inflammatory based liver diseases.

The Potential Of Antisense Oligonucleotides (ASO) Through Inhalation Based On Gold Nanoparticle (AuNP) Delivery System In Inhibiting SARS-CoV-2 Replication And Transcription

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This virus infects the respiratory, digestive, and nervous systems with a rapid transmission and a fairly high mortality rate. However, there has been no specific therapy to treat COVID-19. Previous studies have shown that antisense oligonucleotide (ASO) has good efficacy in DNA and RNA viral infections. This literature review aims to investigate the potential of inhaled ASO based on gold nanoparticles (AuNp) delivery system in inhibiting the replication and transcription of SARS-CoV-2. Literature searching using several databases, such as Google Scholar, Science Direct, ResearchGate, and NCBI. Inclusion and exclusion criteria are used to eliminate the journals that does not match the criteria, thus 28 journals are obtained. The results show that ASO has the potential to inhibit the replication and transcription of the SARS-CoV-2 virus through different mechanisms by binding to the target RNA and modulating the viral protein synthesis. One form of ASO modification that is often used is LNA GapmeR. LNA GapmeR stimulates viral RNA cleavage and can be administered by inhalation with nebulized ASO solution. AuNP as an ASO delivery system through inhalation can reduce toxicity and increase ASO concentrations in reaching target cells. Therefore, ASO therapy with AuNP through inhalation needs to be considered for COVID-19 treatment. Further clinical study about the ideal delivery system and optimal dosage of ASO based AuNP via inhalation for COVID-19 are needed to investigate soon.

Orally Administered Amphotericin B Nanoformulations: Physical Properties of Nanoparticle Carriers on Bioavailability and Clinical Relevance.

Amphotericin B is an effective polyene antifungal considered as a “gold standard” in the management of fungal infections. Currently, it is administered mainly by IV due to poor aqueous solubility, which precludes its delivery orally. Paradoxically, IV administration is akin to side effects that have not been fully eliminated even with more recent IV formulations. Thus, the need for alternative formulations/route of administration for amphotericin B remains crucial. The oral route offers the possibility of delivering amphotericin B systemically and with diminished side effects; however, enterocyte permeation remains a constraint. Cellular phagocytosis of submicron particles can be used to courier encapsulated drugs. In this regard, nanoparticulate delivery systems have received much attention in the past decade. This review examines the trajectory of orally delivered amphotericin B and discusses key physical factors of nanoformulations that impact bioavailability. The review also explores obstacles that remain and gives a window into the possibility of realizing an oral nanoformulation of amphotericin B in the near future.

A model system for antiviral siRNA therapeutics using exosome-based delivery

Emerging viral diseases, such as Ebola, SARS, MERS, and the pathogen causing COVID-19, SARS-CoV-2, present a challenge for the development of therapeutics because of strict biosafety handling procedures and rapid mutation of their genomes. To facilitate the development of an adaptable and testable therapeutic model system, a colostrum exosome-based nanoparticle delivery system, EPM (exosome-PEI matrix), that overcomes stringent biosafety containment, was used to mimic the expression of viral proteins. This system would greatly expand the number of laboratories actively participating in the screening of potential therapeutics. EPM technology can deliver both plasmid DNA and siRNA to both simulate viral gene expression and screen potential antiviral siRNA therapeutics. Using this nanoplatform, three key SARS-CoV-2 proteins (the spike glycoprotein, nucleocapsid, and replicase) were expressed in vitro and in vivo. In vitro, several viral gene-targeting siRNAs were screened to determine knockdown efficiency, with some siRNA duplexes resulting in 80%–95% knockdown of corresponding protein expression. Moreover, in vivo experiments introducing the spike protein and nucleocapsid by EPM resulted in the production of antibodies against the viral antigen, measured up to 45 d after target delivery. Together, these findings support the efficacy of the EPM delivery system to establish a model for screening antiviral therapeutics-reduced biosafety level.

A Hoechst Reporter Enables Visualization of Drug Engagement In Vitro and In Vivo: Toward Safe and Effective Nanodrug Delivery.

Assessment of drug activation and subsequent interaction with targets in living tissues could guide nanomedicine design, but technologies enabling insight into how a drug reaches and binds its target are limited. We show that a Hoechst-based reporter system can monitor drug release and engagement from a nanoparticle delivery system in vitro and in vivo, elucidating differences in target-bound drug distribution related to drug-linker and nanoparticle properties. Drug engagement is defined as chemical detachment of drug or reporter from a nanoparticle and subsequent binding to a subcellular target, which in the case of Hoechst results in a fluorescence signal. Hoechst-based nanoreporters for drug activation contain prodrug elements such as dipeptide linkers, conjugation handles, and nanoparticle modifications such as targeting ligands to determine how nanomedicine design affects distribution of drug engaged with a subcellular target, which is tracked via cellular nuclear fluorescence in situ. Furthermore, the nanoplatform is amenable toward common maleimide-based linkers found in many prodrug-based delivery systems including polymer-, peptide-, and antibody-drug conjugates. Findings from the Hoechst reporter system were applied to develop highly potent, targeted, anticancer micelle nanoparticles delivering a monomethyl auristatin E (MMAE) prodrug comprising the same linkers employed in Hoechst studies. MMAE nanomedicine with the optimal drug-linker resulted in effective tumor growth inhibition in mice without associated acute toxicity, whereas the nonoptimal linker that showed broader drug activation in Hoechst reporter studies resulted in severe toxicity. Our results demonstrate the potential to synergize direct visualization of drug engagement with nanomedicine drug-linker design to optimize safety and efficacy.

Lactobacillus cell envelope-coated nanoparticles for antibiotic delivery against cariogenic biofilm and dental caries

BackgroundDue to their prevalence, dental caries ranks first among all diseases endangering human health. Therefore, the prevention of caries is of great significance, as caries have become a serious public health problem worldwide. Currently, using nanoscale drug delivery systems to prevent caries has received increased attention. However, the preventive efficacy of these systems is substantially limited due to the unique physiological structure of cariogenic biofilms. Thus, novel strategies aimed at combating cariogenic biofilms to improve preventive efficiency against caries are meaningful and very necessary. Herein, inspired by cell membrane coating technology and Lactobacillus strains, we coated triclosan (TCS)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TCS@PLGA-NPs) with an envelope of Lactobacillus (LA/TCS@PLGA-NPs) and investigated their potential as a nanoparticle delivery system against cariogenic biofilms and dental caries.ResultsLA/TCS@PLGA-NPs were successfully prepared with favorable properties, including a coated envelope, controllable size, negative charge, sustained drug-release kinetics and so on. The LA/TCS@PLGA-NPs inherited native properties from the source cell surface, thus the LA/TCS@PLGA-NPs adhered to S. mutans, integrated into the S. mutans biofilm, and interfered with the biofilm formation of S. mutans. The nanoparticles significantly inhibited the activity, biomass and virulence gene expression of S. mutans biofilms in vitro. Additionally, LA/TCS@PLGA-NPs exhibited a long-lasting inhibitory effect on the progression of caries in vivo. The safety performance of the nanoparticles is also favorable.ConclusionsOur findings reveal that the antibiofilm effect of LA/TCS@PLGA-NPs relies not only on the inheritance of native properties from the Lactobacillus cell surface but also on the inhibitory effect on the activity, biomass and virulence of S. mutans biofilms. Thus, these nanoparticles could be considered feasible candidates for a new class of effective drug delivery systems for the prevention of caries. Furthermore, this work provides new insights into cell membrane coating technology and presents a novel strategy to combat bacterial biofilms and associated infections.Graphical

Erythrocyte Membrane-Enveloped Salvianolic Acid B Nanoparticles Attenuate Cerebral Ischemia-Reperfusion Injury.

PurposeIschemic stroke is the second leading cause of death and the third leading cause of disability worldwide. Salvianolic acid B (SAB), a water-soluble phenolic acid derived from the traditional Chinese medicine Salvia miltiorrhiza, exerted protective effects on cerebral ischemia-reperfusion injury. However, the efficacy of SAB is seriously hindered by poor blood brain barrier (BBB) permeability and short biological half-life in plasma. Brain targeted biomimetic nanoparticle delivery systems offer much promise in overcoming these limitations.MethodsA brain targeted biomimetic nanomedicine (RR@SABNPs) was developed, which comprised of SAB loaded bovine serum albumin nanoparticles and functionalized red blood cell membrane (RBCM) with Arg-Gly-Asp (RGD). The characterization parameters, including particle size, zeta potential, morphology, Encapsulation Efficiency (EE), Drug Loading (DL), release behavior, stability, and biocompatibility, were investigated. Moreover, the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was used to assess the therapeutic efficacy of RR@SABNPs on ischemic stroke. Finally, the reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were detected by DHE and JC‑1 staining in oxygen-glucose deprivation/reperfusion (OGD/R) and H2O2 injured PC12 cells.ResultsRR@SABNPs exhibited spheric morphology with core-shell structures and good stability and biocompatibility. Meanwhile, RR@SABNPs can significantly prolong SAB circulation time by overcoming the reticuloendothelial system (RES) and actively targeting ischemic BBB. Moreover, RR@SABNPs had comprehensive protective effects on MCAO/R model mice, manifested as a reduced infarct volume and improved neurological and sensorimotor functions, and significantly scavenged excess ROS and maintained MMP.ConclusionThe designed brain targeted biomimetic nanomedicine RR@SABNPs can significantly prolong the half-time of SAB, deliver SAB into the ischemic brain and exhibit good therapeutic effects on MCAO/R model mice.

A simple but efficient tumor-targeted nanoparticle delivery system constructed by oleic acid

Oleic acid (OA) is a kind of monounsaturated omega-3 fatty acid that abounds in plants and animals which can induce apoptosis and has broad-spectrum inhibitory activity against a variety of tumor cell lines. However, OA is quite insoluble and thus inconvenient to be efficiently delivered in vivo. In this work, OA was fabricated into nanoparticles to generate OA elastic nanoparticles (OA-ENPs) with a particle size of 185.6 nm and good stability in various physiological media. OA-ENPs alone achieved a high tumor inhibition rate of 60.3% without significant side effect. More surprisingly, the resultant OA-ENPs displayed dose-dependent tumor targetability. Low dose of OA-ENPs (10 mg/kg) mainly distributed in the liver after intravenous injection, while high dose of OA-ENPs mainly distributed in tumor. At the high dose of 90 mg/kg, OA-ENPs accumulation in tumor reached nearly twice as that in the liver. Here we provide a simple but effective way to achieve excellent tumor targetability without the need of any surface modification of nanoparticles.

Starch-based NP act as antigen delivery systems without immunomodulating effect.

The nasal route of immunization has become a real alternative to injections. It is indeed described as more efficient at inducing immune protection, since it initiates both mucosal and systemic immunity, thus protecting against both the infection itself and the transmission of pathogens by the host. However, the use of immunomodulators should be limited since they induce inflammation. Here we investigated in vitro the mechanisms underlying the enhancement of antigen immunogenicity by starch nanoparticles (NPL) delivery systems in H292 epithelial cells, as well as the NPL’s immunomodulatory effect. We observed that NPL had no intrinsic immunomodulatory effect but enhanced the immunogenicity of an E. coli lysate (Ag) merely by increasing its intracellular delivery. Moreover, we demonstrated the importance of the NPL density on their efficiency by comparing reticulated (NPL) and non-reticulated particles (NPL·NR). These results show that an efficient delivery system is sufficient to induce a mucosal immune response without the use of immunomodulators.