Chitosan-coated Poly Research Articles

Mannose-Functionalized Chitosan-Coated PLGA Nanoparticles for Brain-Targeted Codelivery of CBD and BDNF for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative disease causing cognitive and memory decline. AD is characterized by the deposition of amyloid-β and hypophosphorylated forms of tau protein. AD brains are found to be associated with neurodegeneration, oxidative stress, and inflammation. Cannabidiol (CBD) shows neuroprotective, antioxidant, and anti-inflammatory properties and simultaneously reduces amyloid-β production and tau hyperphosphorylation. The brain-derived neurotrophic factor (BDNF) plays a vital role in the development and maintenance of the plasticity of the central nervous system. A decline of BDNF levels in AD patients results in reduced plasticity and neuronal cell death. Current therapeutics against AD are limited to only symptomatic relief, necessitating a therapeutic strategy that reverses cognitive decline. In this scenario, combination therapy of CBD and BDNF could be a fruitful strategy for the treatment of AD. We designed mannose-conjugated chitosan-coated poly(d,l-lactide-co-glycolide (PLGA) (CHTMAN-PLGA) nanoparticles for the codelivery of CBD and BDNF to the brain. Chitosan is modified with mannose to specifically target the glucose transporter-1 (GLUT-1) receptor abundantly present in the blood-brain barrier for selectively delivering therapeutics to the brain. The CBD-encapsulated nanoparticles showed an average hydrodynamic diameter of 306 ± 8.12 nm and a zeta potential of 31.7 ± 1.53 mV. The coated nanoparticles prolonged encapsulated CBD release from the PLGA matrix. The coated nanoparticles exhibited sustained release of CBD for up to 22 days with 91.68 ± 2.91% release of the encapsulated drug. The coated nanoparticles, which had a high positive zeta potential (31.7 ± 1.53 mV), encapsulated the plasmid DNA. The qualitative transfection efficiency was investigated using CHTMAN-PLGA-CBD/pGFP in bEND.3, primary astrocytes, and primary neurons, while the quantitative transfection efficiency of the delivery system was determined using CHTMAN-PLGA-CBD/pBDNF. In vitro, the pBDNF transfection study revealed that the BDNF expression was 4-fold higher for CHTMAN-PLGA-CBD/pBDNF than for naked pBDNF in all of the cell lines. The cytotoxicity and hemocompatibility of the designed nanoparticles were tested in bEND.3 cells and red blood cells, respectively, and the nanoparticles were found to be nontoxic and hemocompatible. Hence, mannose-conjugated chitosan-coated PLGA nanoparticles could be useful as brain-targeting delivery vehicles for the codelivery of CBD and BDNF for possible AD treatment.

Optimization and evaluation of a chitosan-coated PLGA nanocarrier for mucosal delivery of Porphyromonas gingivalis antigens

Recent advances in understanding Alzheimer's disease (AD) suggest the possibility of an infectious etiology, with Porphyromonas gingivalis emerging as a prime suspect in contributing to AD. P. gingivalis may invade systemic circulation via weakened oral/intestinal barriers and then cross the blood-brain barrier (BBB), reaching the brain and precipitating AD pathology. Based on the proposed links between P. gingivalis and AD, a prospective approach is the development of an oral nanovaccine containing P. gingivalis antigens for mucosal delivery. Targeting the gut-associated lymphoid tissue (GALT), the nanovaccine may elicit both mucosal and systemic immunity, thereby hampering P. gingivalis ability to breach the oral/intestinal barriers and the BBB, respectively.The present study describes the optimization, characterization, and in vitro evaluation of a candidate chitosan-coated poly(lactic-co-glycolic acid) (PLGA-CS) nanovaccine containing a P. gingivalis antigen extract. The nanocarrier was prepared using the double emulsion solvent evaporation method and optimized for selected experimental factors, e.g. PLGA amount, surfactant concentration, w1/o phase ratio, applying a d-optimal statistical design to target the desired physicochemical criteria for its intended application. After nanocarrier optimization, the nanovaccine was characterized in terms of particle size, polydispersity index (PdI), ζ-potential, encapsulation efficiency (EE), drug loading (DL), morphology, and in vitro release profile, as well as for mucoadhesivity, stability under simulated gastrointestinal conditions, antigen integrity, in vitro cytotoxicity and uptake using THP-1 macrophages.The candidate PLGA-CS nanovaccine demonstrated appropriate physicochemical, mucoadhesive, and antigen release properties for oral delivery, along with acceptable levels of EE (55.3 ± 3.5 %) and DL (1.84 ± 0.12 %). The integrity of the encapsulated antigens remained uncompromised throughout NPs production and simulated gastrointestinal exposure, as confirmed by SDS-PAGE and Western blotting analyses. Furthermore, the nanovaccine showed effective in vitro uptake, while exhibiting low cytotoxicity. Taken together, these findings underscore the potential of PLGA-CS NPs as carriers for adequate antigen mucosal delivery, paving the way for further investigations into their applicability as vaccine candidates against P. gingivalis.

Nasally delivered chitosan-coated poly(lactide-co-glycolide) encapsulating honeybee venom enhances T helper 1-related immunity against Salmonella Typhimurium infection in pigs.

Salmonella Typhimurium is a significant zoonotic concern for human food poisoning and a substantial economic burden in the swine industry. We previously reported that nasally delivered chitosan-coated poly(lactide-co-glycolide) (PLGA) encapsulating honeybee venom (CP-HBV) could enhance CD4+ T helper 1 (Th1)-related immune responses in healthy pigs. Building upon these findings, the current study aimed to investigate the protective immune enhancement by nasally delivered CP-HBV in pigs challenged with S Typhimurium. 36 healthy, 4-week-old, female, Landrace X Yorkshire X Duroc pigs. 36 pigs were allocated into 3 groups: CP-HBV (n = 16), control (n = 16), and healthy baseline control (n = 4). CP-HBV and control groups were challenged with S Typhimurium 7 days post-treatment. Pigs from the healthy control group were sacrificed at 0 days postinfection (DPI), and 4 pigs from each of the control and CP-HBV groups were sacrificed at 1, 2, 4, and 7 DPI. Salmonella shedding, immune cell frequencies, cytokines, and transcriptional factor expression levels were measured. The CP-HBV group exhibited lower bacterial shedding and an enhanced Th1-related immune response characterized by an upregulation of CD4+ T cells and CD4+ Interferon-γ+ T cells, accompanied by increased expression of Th1-related cytokines and reduced expression of regulatory T cells and immunosuppressive cytokines compared to the control group. CP-HBV is a promising strategy for controlling Salmonella infections in pigs and improving public health.

Controlled release of Amoxicillin from chitosan-coated poly(lactic-co-glycolic acid) nanoparticles

Controlled release of Amoxicillin from chitosan-coated poly(lactic-co-glycolic acid) nanoparticles

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus

The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.

Chitosan-Coated Poly(lactic-co-glycolic acid) Nanoparticles Loaded with Ursolic Acid for Breast Cancer Therapy

Chitosan-Coated Poly(lactic-<i>co</i>-glycolic acid) Nanoparticles Loaded with Ursolic Acid for Breast Cancer Therapy

Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity.

Recent studies suggest that the association of antigens in microparticles increases the anti-Leishmania vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly(D,L-lactic) acid submicrometric particles (SMP) and analyze the inflammatory profile and toxicity. Two formulations were selected, SMP1, containing poly(D,L-lactide) (PLA) 1% wt/v and chitosan 1% wt/v; and SMP2, containing PLA 5% wt/v and chitosan 5% wt/v. After a single dose of the unloaded SMP1 or SMP2 in mice, the SMPs promoted cell recruitment without tissue damage. In addition, besides the myeloperoxidase (MPO) activity having demonstrated similar results among the analyzed groups, a progressive reduction in the levels of N-acetyl-β-D-glucosaminidase (NAG) until 72 h was observed for SMPs. While IL-6 levels were similar among all the analyzed groups along the kinetics, only the SMPs groups had detectable levels of TNF-α. Additionally, the Leishmania braziliensis antigen was encapsulated in SMPs (SMP1Ag and SMP2Ag), and mice were vaccinated with three doses. The immunogenicity analysis by flow cytometry demonstrated a reduction in NK (CD3-CD49+) cells in all the SMPs groups, in addition to impairment in the T cells subsets (CD3+CD4+) and CD3+CD8+) and B cells (CD19+) of the SMP2 group. The resulting data demonstrate that the chitosan-coated SMP formulations stimulate the early events of an innate immune response, suggesting their ability to increase the immunogenicity of co-administered Leishmania antigens.

PH-dependent, extended release and enhanced in vitro efficiency against colon cancer of Tegafur formulated using chitosan-coated poly(ε-caprolactone) nanoparticles

Tegafur is used to treat various malignant lesions, including advanced gastric and colorectal cancers. However, its efficacy is limited by its low oral bioavailability, short half-life and serious toxicity. To address these drawbacks, a nanoformulation of poly(ε-caprolactone) nanoparticles coated with chitosan was developed for the delivery of Tegafur. Poly(ε-caprolactone) particles were prepared by an interfacial polymer disposition method, while surface functionalization with chitosan followed a coacervation procedure. Transmission electron microscopy and elemental analyses, and electrokinetics of the particles demonstrated that such core/shell nanostructure was obtained. Compared to unmodified particles, chitosan-coated nanoparticles demonstrated a substantially increased stability at both 4 and 25 °C over 30 days. Particles showed an encapsulation efficiency of ≈64% and a pH-dependent behavior in which complete Tegafur release was extended over 168, 48 or 24 h at pH 7.4 (blood), 6.5 (extracellular microenvironment of tumors) or 5.5 (endosomes/lysosomes of tumor cells), respectively. Based on hemocompatibility and cell viability tests, chitosan-coated nanoparticles exhibited satisfactory biocompatibility and safety for drug delivery. Furthermore, Tegafur-loaded chitosan-decorated particles demonstrated enhanced anticancer efficiency, with half maximal inhibitory concentration values in HT-29 and T-84 cells of ≈ 4-fold and ≈3.5-fold less than that of the free drug and drug-loaded unmodified nanoparticles, respectively. In vivo studies are needed to fully assess their efficacy and safety.

Apocynin-loaded PLGA nanomedicine tailored with galactosylated chitosan intrigue asialoglycoprotein receptor in hepatic carcinoma: Prospective targeted therapy

Nature serves as a priceless source for phytomedicines to treat different types of cancer, including hepatocellular carcinoma (HCC). Apocynin (APO), an anti-cancer phytomedicine, is a particular nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase) inhibitor, which has recently dawned for its multilateral pharmacological activities. As far as we are aware, no investigation has been carried out yet to develop a targeted-nanostructured delivery system of APO to HCC. Consequently, chitosan derivative with galactose groups namely; galactosylated chitosan (GC), particularly recognized by the asialoglycoprotein receptor (ASGR), was synthesized and its chemical structure was thoroughly characterized by substantial techniques. Afterwards, GC-coated nanoplatform for hepatocyte attachment “APO-loaded galactosylated chitosan-coated poly(d,l-lactide-co-glycolide) nanoparticles (APO-loaded GC-coated PLGA NPs)” was developed. The prosperous APO-loaded GC-coated PLGA NPs would be comprehensively appraised through extensive investigations. Their solid state characterization using Fourier transform-infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry proved APO’s encapsulation in the polymeric matrix. Transmission electron microscopy imaging of the investigated NPs highlighted their spherical architecture with a nanosized range and a characteristic halo-like appearance traceable to the GC coating of the NPs' surface. Saliently, the results of in vitro cytotoxicity screening revealed the spectacular anti-cancer efficacy of APO-loaded GC-coated PLGA NPs formula against the HepG2 cell line. Moreover, the fluorescence microscope disclosed the distinguished cellular uptake of such formula via ASGPR mediated endocytosis. Inclusively, a multifunctional nano-phytomedicine delivery system with a promising active hepatocyte-targeting, effective uptake into HepG2 cells, and sustained drug release pattern was successfully developed.

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.

One-pot self-assembly fabrication of chitosan coated hollow sphere for pH/ glutathione dual responsive drug delivery

Chitosan-coated poly (methacrylic acid) (PMAA) hollow spheres with 64 ± 3% drug loading capacity and low drug leakage (7 ± 2%, 54 h) were prepared through a novel one-pot two-step self-assembly process. Site-specific doxorubicin (DOX) loading and chitosan coating were achieved by electrostatic interaction to fulfill efficient drug loading and well-controlled drug release behavior. In vitro drug release profile revealed the pH and glutathione (GSH) dual responsive fast triggered drug release behavior, reaching 62 ± 3% during the first 10 h. And completely drug release could be achieved in 54 h. The high drug content and sensitive tumor microenvironment responsibility lead to similar anti-cancer efficiency with free doxorubicin in in vitro MTT assay. This self-assembly guided one-pot two-step fabrication process was proved to be an effective and convenient way to prepare the well-defined multi-layer structure and might be further employed in fabricating high-performance drug delivery systems.

In vivo and in vitro per se effect evaluation of Polycaprolactone and Eudragit® RS100-based nanoparticles

Biodegradable polymeric nanocapsules (NC) present incredible characteristics as drug nanocarriers that optimize drug targeting. However, However, a more detailed isolated effect of polymer-based nanoparticles as drug carriers is required. This work aimed to evaluate the per se effect of blank-NC (NC-B) with different surface characteristics both in vitro and in vivo toxicity. NC1-B (Polysorbate 80 coated poly(ɛ-caprolactone) NC), NC2-B (polyethylene glycol 6000 coated poly(ɛ-caprolactone) NC), NC3-B (chitosan-coated poly(ɛ-caprolactone) NC) and NC4-B (Eudragit® RS100 NC) were prepared by nanoprecipitation method. Formulations were characterized by particle size, zeta potential, and pH. The in vitro cytotoxicity tests against tumor cell lines were performed (HepG2 and MCF-7). Antiviral activity was evaluated by MTT in Vero cells infected with HSV-1 (KOS strain). In vivo evaluation was performed in apomorphine-induced stereotypy in Wistar rats and locomotor activity distance, head movements, and rearing behavior were measured. NC1-B, NC2-B, NC3-B, and NC4-B had a diameter under 350 nm. The pH and zeta potential of formulations varied according to their coating. For in vitro evaluation of antitumor activity and antiviral activity, one-way ANOVA showed no significant differences in cell viability. In vivo tests showed low neurological effects. In conclusion, different surface characteristics of NC-B did not demonstrate toxicity against the evaluated cell lines HepG2 and MCF-7, antiviral effect against HSV-1, and the neurological effects in a stereotyping model were low and may be attributed to the per se effect of NC-B.

Chitosan-coated poly (lactic-co-glycolide) nanoparticles for dual delivery of doxorubicin and naringin against MCF-7 cells

Present investigation examines the simultaneous encapsulation and delivery of DOX and NAR through PLGA-NPs and CS-coated PLGA-NPs to improve the efficacy and synergistic anticancer activity of DOX, and reduce its toxicity. Drug-loaded F3 and F4 were prepared by double-emulsion solvent-evaporation technique. PS, PDI, ZP and morphology of the NPs were determined using Zetasizer and SEM, respectively. %EE and %DL of both drugs were determined by indirect method. Dialysis tubing was used for in vitro release studies in phosphate buffer saline (pH 6.8) with SLS (0.1% w/v). Storage stability of the NPs was performed at 30 °C for 6-months. In vitro cytotoxicity was determined by MTT-assay, using MCF-7 cells. Cytotoxic effects of the NPs were also observed by visualizing the morphological changes in MCF-7 cells. PS, PDI and ZP of F4 were 366.8 ± 36.7 nm, 0.352 ± 0.033 and +35.57 ± 4.25 mV, respectively and those of F3 were 302.2 ± 45.4 nm, 0.283 ± 0.016 and −4.69 ± 2.66 mV. Increased PS and high positive ZP were found after CS-coating. Smooth-surfaced PLGA-NPs were observed by SEM, and slightly rough-surfaced NPs were found after CS-coating. %EE and %DL for DOX were 66.01%, 4.26% and 76.26%, 3.28% in F3 and F4, respectively. For NAR, these values were 77.82%, 3.22% and 71.85%, 4.64% in F3 and F4. The in vitro release profile revealed a sustained delivery of the drugs with 51% and 63% of DOX, as well as 80% and 78% of NAR at 48 h, from F3 and F4, respectively. Relatively high amounts of DOX and NAR were rapidly released from DOX-NAR-AqS at 2 h only. Release kinetic investigations justify the sustained release property of F3 and F4, and they followed the “Korsmeyer-Peppas model”. Release-exponent values suggest that the mechanism of the drug(s) release was Fickian-diffusion. Stability study revealed acceptable physicochemical changes for 6-months F4 showed the highest cytotoxicity (IC50, 1.52 μg/mL), when compared to F3, free DOX-NAR combination and DOX alone. Cytotoxicity and cell morphology represented the highest cellular uptake of F4. Conclusively, F4 could be an effective nano-carrier for DOX and NAR to improve their encapsulation, sustain their release, stability and simultaneous delivery against MCF-cells.

Chitosan-coated poly (Ɛ-caprolactone) nanoparticles as acaricide carriers

Among many species of ticks that affect beef and dairy cattle, Rhipicephalus (Boophilus) microplus is the most common. It is responsible for heavy losses in milk and meat production. In this work we introduce nanostructures such as chitosan-poly-Ɛ-caprolactone (CS_PCL) nanoparticles to encapsulate amitraz (CS_PCLnp_Amitraz) and fluazuron (CS_PCLnp_Fluazuron) to treat tick infestations more effectively. The CS_PCLnp_Amitraz system has a final amitraz concentration of 1.0 mg/mL with a particle size of 275 ± 30 nm, surface charge of +43 ± 7 mV and entrapment efficiency of 77 ± 1%. The CS_PCLnp_Fluazuron system has a drug concentration of 0.5 mg/mL with a particle size of 295 ± 35 nm, surface charge of +45 ± 10 mV and entrapment efficiency of 89 ± 1%. Both systems reduced cytotoxicity on Balb/c 3T3 culture cells and were also active against R. microplus. Both molecules - amitraz and fluazuron – formed molecularly dispersed active compounds inside the core of the PCL polymer matrix. The PCL surface was composed of a chitosan layer, which influenced the stability of the steric nanoparticles at pH greater than 7. Both systems were stable at a saline concentration of 1.25 mol/L and at temperatures below 50 °C. Experiments conducted in vivo with CS_PCLnp_Amitraz, at doses of active ingredient equivalent to those of commercial products, showed decreased tick infestation for 21 days, as well as higher acaricide effect than observed for commercial products, which recommend a reapplication in 14 days. The acaricide effect was even stronger when CS_PCLnp_Amitraz (same dose as for commercial products) and CS_PCLnp_Fluazuron (half of the amount for commercial products) were administered together.

Chitosan-Coated Poly(lactic acid) Nanofibres Loaded with Essential Oils for Wound Healing.

Chronic skin wounds are characterised by a non-healing process that makes necessary the application of wound dressings on the damaged area to promote and facilitate the recovery of skin’s physiological integrity. The aim of the present work is to develop a bioactive dressing that, once applied on the injured tissue, would exert antibacterial activity and promote adhesion and proliferation of fibroblasts. Nanofibres consisting of poly(lactic acid) (PLA) and essential oils (EOs) were electrospun and coated with a medium molecular weight chitosan (CS). Black pepper essential oil (BP-EO) or limonene (L), well-known for their antibacterial properties, were added to the PLA/acetone solution before electrospinning; phase separation phenomena occurred due to the poor solubility of the EOs in the PLA solution and led to fibres having surface nano-pores. The porous electrospun fibres were coated with CS to produce hydrophilic membranes that were easy to handle, biocompatible, and suited to promote cellular proliferation. The fibrous scaffolds were tested in terms of mechanical resistance, wettability, antibacterial activity, in-vitro cytotoxicity, and ability to promote fibroblasts’ adhesion and proliferation. The results obtained proved that the CS coating improved the hydrophilicity of the fibrous mats, enhanced EO’s antibacterial potential, and promoted cell adhesion and proliferation.

Chitosan coated nanoparticles for efficient delivery of bevacizumab in the posterior ocular tissues via subconjunctival administration

In several ocular diseases, vascular endothelial growth factor (VEGF) level has been found to be unregulated. Bevacizumab, an anti-VEGF drug, is the most commonly used off level drug for diabetic retinopathy (DR). The present study was to evaluate the chitosan-coated poly (lactide-co-glycolic acid) nanoparticles (CS-PLGA NPs) for sustained and effective delivery of bevacizumab to posterior ocular tissues. The penetration of NP through sclera was studied by confocal laser scanning microscopy (CLSM). For pharmacokinetic study, bevacizumab loaded NPs were administered into the rat eye through subconjunctival injection (SCJ) and pharmacokinetic parameters were compared to drug solution. CLSM and pharmacokinetic study showed better penetration of formulation and higher concentration of bevacizumab in posterior ocular tissues. In retinopathy model, CS-PLGA NPs by SCJ route showed more reduction of VEGF level in retina than the topical and intravitreal administration of formulation. Thus, CS-coated PLGA NPs can be potentially useful as carriers to target retina.

Chitosan-coated poly(є-caprolactone) nanocapsules for mucoadhesive applications of perillyl alcohol

ABSTRACT Perillyl alcohol (POH) is an essential oil found in several plants and presents significant therapeutic and chemo-preventive activity against some tumors. However, it exhibits low aqueous solubility and thereby reduced oral absorption and bioavailability. Nanoencapsulation of POH can be an important tool to overcome such limitations. In this work, chitosan was used for coating poly (ε-caprolactone) nanocapsules for mucoadhesive applications of POH. The nanocapsules were obtained by the nanoprecipitation method and presented a mean diameter of about 330 nm, spherical morphology, polydispersity index of 0.14, zeta potential of +32 mV, and POH encapsulation efficiency of 56%. POH was prolonged released from nanocapsules. In mucoadhesion studies, nanocapsules showed higher adsorption to mucin compared to free POH, possibly due to electrostatic interactions between chitosan and mucin. In the cytotoxicity assay, POH-loaded nanocapsules presented higher IC50 than free POH; however, they were more selective for HT-29 tumor cells than for normal Vero cells. The results demonstrate the potential application of chitosan-coated nanocapsules for the oral administration of POH intended for cancer therapy.

Improved pharmacokinetic and biodistribution of 5-fluorouracil loaded biomimetic nanoerythrocytes decorated nanocarriers for liver cancer treatment

Nanoerythrocytes membrane (NEs) has recently been used to improve pharmacokinetics and biodistribution for successful drug therapy. NEs intended to enhance the drug targeting due to immune evasion and long circulation. In this work, NEs could serve as efficient 5- fluorouracil (5-FU) carriers to target liver cells. NEs decorated 5-FU-loaded chitosan coated-poly (lactide-co-glycolic acid) nanoparticles (5-FU-C-NPs-NEs), chitosomes (5-FU-C-LPs-NEs) and 5-FU-NEs were prepared by hypotonic lysis and extrusion procedures. Moreover, 5-FU loaded-chitosan coated 5-FU-NPs (5-FU-C-NPs) and chitosomes (5-FU-C-LPs) for the compared issues were prepared. They were characterized in terms of particle size, encapsulation efficiency (EE), membrane protein content, phosphatidylserine exposure, surface morphology, and in vitro release profiles. Also, their cytotoxic efficacy was determined. Furthermore, pharmacokinetics and biodistribution studies were investigated for optimized formulation. The results revealed that 5-FU-C-NPs-NEs have narrow particle size distribution, desirable EE%, and retained the erythrocyte membrane properties as confirmed by polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, it displayed a sustained release profile up to 72 h of 5-FU-C-NPs-NEs compared to other formulations. In comparison to 5-FU solution and 5-FU-C-NPs, 5-FU-C-NPs-NEs extended the drug release time in vivo with highly uptake by the liver. These results suggest that the 5-FU-C-NPs-NEs could be used to deliver 5-FU and enhance its targetability to liver cancer.

Establishing the promising role of novel combination of triple therapeutics delivery using polymeric nanoparticles for Triple negative breast cancer therapy.

Introduction: Triple-negative breast cancer (TNBC) is a lethal tumor with an advanced degree of metastasis and poor survivability as compared to other subtypes of breast cancer. TNBC which consists of 15 % of all types of breast cancer is categorized by the absence of expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER2). This is the main reason for the failure of current hormonal receptor-based therapies against TNBCs, thus leading to poor patient outcomes. Therefore, there is a necessity to develop novel therapies targeting this devastating disease. Methods: In this study, we have targeted TNBC by simultaneous activation of apoptosis through DNA damage via cytotoxic agent such as paclitaxel (PAC), inhibition of PARP activity via PARP inhibitor, olaparib (OLA) and inhibiting the activity of FOXM1 proto-oncogenic transcription factor by using RNA interference technology (FOXM1-siRNA) in nanoformulations. Experiments conducted in this investigation include cellular uptake, cytotoxicity and apoptosis study using MDA-MB-231 cells. Results: The present study validates that co-delivery of two drugs (PAC and OLA) along with FOXM1-siRNA by cationic NPs, enhances the therapeutic outcome leading to greater cytotoxicity in TNBC cells. Conclusion: The current investigation focuses on designing a multifunctional drug delivery platform for concurrent delivery of either PAC or PARP inhibitor (olaparib) and FOXM1 siRNA in chitosan-coated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with the ability to emerge as a front runner therapeutic for TNBC therapy.

Comparison of immune responses in guinea pigs by intranasal delivery with different nanoparticles-loaded FMDV DNA vaccine

To compare different nanoparticle-based nasal vaccines against foot-and-mouth disease (FMD), chitosan (CS)-coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) (CS/PLGA-NPs) and amino-functionalized mesoporous silica nanoparticles (Am/MSNs) loaded with FMDV recombinant plasmid (pP12A3C/IFN-CS/PLGA-NPs and pP12A3C/IFN-Am/MS-NPs) were used to induce mucosal and systemic immune responses in guinea pigs via intranasal delivery. Simultaneously, CpG oligodeoxy nucleotides (ODNs) as a vaccine adjuvant were encapsulated in chitosan-coated poly (lactic-co-glycolic acid) nanoparticles (CpG-CS/PLGA-NPs). The pP12A3C/IFN-CS/PLGA-NPs and CpG-CS/PLGA-NPs generated displayed good morphology, high stability, mean diameters of 500 and 400 nm and encapsulation efficiencies of 83.8% and 88.4%, respectively. Data from the in vitro release assay showed that plasmid and CpG were sustainably released from nanoparticles (up to 66.73% and 64%, respectively, of the total amount loaded). Guinea pigs immunized with pP12A3C/IFN-CS/PLGA-NPs + CpG-CS/PLGA-NPs showed markedly higher mucosal, cellular and humoral immune responses than those administered pP12A3C/IFN-CS/PLGA-NPs or naked plasmid vaccine alone. FMDV-specific secretory immunoglobulin A (sIgA) antibodies in nasal washes were initially detected at 3 days post-vaccination with CS/PLGA-NPs loaded with plasmid. Guinea pigs immunized with pP12A3C/IFN-CS/PLGA-NPs also displayed higher cellular and humoral immune responses than pP12A3C-CS/PLGA-NPs and naked plasmid vaccine alone. FMDV-specific immunoglobulin G (IgG) antibodies in serum were initially detected at 5 days post-vaccination (intramuscularly) with the naked plasmid. Finally, challenge experiments 42 days post-vaccine revealed 100% protection in guinea pigs immunized with pP12A3C/IFN-CS/PLGA-NPs + CpG-CS/PLGA-NPs and pP12A3C/IFN-CS/PLGA-NPs. However, plasmid DNA was burst released from pP12A3C/IFN-Am/MS-NPs. Our attempts to use pP12A3C/IFN-Am/MS-NPs to immunize guinea pigs failed to induce immune responses. In conclusion, CpG and IFN-α adjuvant based FMD vaccines elicit protection in guinea pigs. Moreover, CS-coated PLGA NPs present an efficient and safe mucosal immune delivery system for FMDV DNA vaccine. Data from the current study provide a foundation for understanding and further evaluating protective immune responses in pigs.