The images illustrate the histopathological condition of nasal mucosa after 2
h exposure of (A, negative control) PBS pH 6.4 (B, positive control) IPA (C) drug solution and (D) drug-loaded NP. The ...arrows in (B) indicate the change in histopathology of the mucosa. Some cilias were detached when treated with drug solution (C). No change in the mucosal histopathology was observed when treated with drug-loaded NP (D).
Olanzapine (OZ) is a second-generation or atypical antipsychotic which selectively binds to central dopamine D
2 and serotonin (5-HT
2c) receptors. It has poor bioavailability due to hepatic first-pass metabolism and low permeability into the brain due to efflux by P-glycoproteins. The present investigation aimed to prepare a nanoparticulate drug delivery system of OZ using poly(lactic
-co-glycolic acid) (PLGA) for direct nose-to-brain delivery to provide brain targeting and sustained release. PLGA nanoparticles (NP) were prepared by the nanoprecipitation technique and characterized by entrapment efficiency, particle size, zeta potential, modulated temperature differential scanning calorimetry (MTDSC) and X-ray diffraction (XRD) studies. The NP were evaluated for
in vitro release,
ex vivo diffusion, toxicity and pharmacokinetic studies. The NP were 91.2
±
5.2
nm in diameter and had entrapment efficiency 68.91
±
2.31%. MTDSC studies indicated broadening of the drug peak and a shift in the polymer peak, possibly due to physical interaction or H-bonding between the carbonyl groups of PLGA and the NH groups of OZ, and also due to the plasticization effect of OZ on PLGA. XRD studies indicated a decrease in the crystallinity of OZ or amorphization.
In vitro drug release showed a biphasic pattern with initial burst release and, later, sustained release (43.26
±
0.156% after 120
h), following the Fickian diffusion-based release mechanism.
Ex vivo diffusion through sheep nasal mucosa showed 13.21
±
1.59% of drug diffusion in 210
min from NP. Histopathological study of sheep nasal mucosa showed no significant adverse effect of OZ-loaded NP.
In vivo pharmacokinetic studies showed 6.35 and 10.86 times higher uptake of intranasally delivered NP than OZ solution delivered through intravenous (IV) and intranasal (IN) route, respectively. These results proved that OZ could be transported directly to the brain after IN delivery of PLGA NP, enhanced drug concentration in the brain and would therefore be effective in improving the treatment of central nervous system disorders.
Various species of the intestinal microbiota have been associated with the development of colorectal cancer
, but it has not been demonstrated that bacteria have a direct role in the occurrence of ...oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin
. This compound is believed to alkylate DNA on adenine residues
and induces double-strand breaks in cultured cells
. Here we expose human intestinal organoids to genotoxic pks
E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.
Effect of RT NPs after intraveneous administration on the escape latency achieved in Morris Water Maze test in saline and scopolamine treated mice.
Sustained release nanoparticulate formulations of ...Rivastigmine tartrate (RT) were prepared, optimized (using factorial design) and characterized using the biodegradable polymers, PLGA and PBCA as carriers. The pharmacodynamic performances of the nanoparticles (NPs) were evaluated for brain targeting and memory improvement in scopolamine-induced amnesic mice using Morris Water Maze Test. PLGA NPs were prepared by nanoprecipitation technique, while PBCA NPs were prepared by emulsion polymerization technique. Effect of key formulation variables on particle size (PS) and percentage drug entrapment (PDE) of NPs was studied by using factorial design. PLGA NPs showed PS of 135.6
±
4.2
nm and PDE of 74.46
±
0.76 %, whereas PBCA NPS showed PS of 146.8
±
2.6
nm and PDE of 57.32
±
0.91%. FTIR and GPC characterization confirmed complete polymerization of
n-butyl cyanoacrylate (nBCA) monomer into PBCA. DSC thermograms indicated that RT was dispersed as amorphous state in both PLGA and PBCA NPs. TEM studies indicated that the NPs were spherical.
In vitro studies showed 30.86
±
2.07% and 43.59
±
3.80% release from PLGA and PBCA NPs in 72
h, respectively. Pharmacodynamic study demonstrated faster regain of memory loss in amnesic mice with both PLGA and PBCA NPs when compared to RT solution. This indicates rapid and higher extent of transport of RT into the mice brain and thus shows the suitability of both NPs as potential carriers for providing sustained brain delivery of RT.
MXenes have developed as an astonishing family of 2D layered materials that have piqued the interest of scientists from a wide range of scientific disciplines. The amalgamation of characteristics ...distinguishes MXenes from other materials, including their excellent electrical conductivity, hydrophilicity due to functionalized surfaces, higher negative zeta potential, and ability to support stable colloidal solutions in water, which has enabled a wide range of applications. Scientists have been compelled to examine the terahertz absorption characteristics of MXenes since 2019 due to their amazing microwave attenuation efficacy, large specific surface area (SSA), fragility, good strength, varied electromagnetic (EM) response, precise layer spacing, and strong internal conductivity, which have been demonstrated to greatly increase terahertz absorption. Regardless of the type of filler utilized, the reflection of produced composites is often insignificant compared to the overall effectiveness of shielding. This suggests that the dominant shielding mechanism appears to be the absorption component, which is the difference between the total shielding efficacy and its reflection component. The shielding efficiency of graphene composites is greater than 40 dB for frequencies greater than 2.2 THz, whereas that of MXene composites is lower than 10 dB for the entire frequency range under study, necessitating further investigation to create MXene-based composites with higher shielding efficiency. In view of the lack of reviews on MXene (2D materials) with terahertz absorption properties, here we review all of the data on MXenes—primarily based on terahertz-absorbing composites—and provide a modern-day examination of MXenes as terahertz absorbers, their fabrication and their expanding application in a variety of fields.
Graphical Abstract
The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live ...attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its own advantages and disadvantages. The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response. In this regard, nanotechnology is greatly contributing to developing efficient vaccine adjuvants and delivery systems. These can protect the encapsulated antigen from the host's in-vivo environment and releasing it in a sustained manner to induce a long-lasting immunostimulatory effect. In view of this, the present review article summarizes nanoscale-based adjuvants and delivery vehicles such as viral vectors, virus-like particles and virosomes; non-viral vectors namely nanoemulsions, lipid nanocarriers, biodegradable and non-degradable nanoparticles, calcium phosphate nanoparticles, colloidally stable nanoparticles, proteosomes; and pattern recognition receptors covering c-type lectin receptors and toll-like receptors.
A great deal of effort has been made over the years to develop liposomes that have targeting vectors (oligosaccharides, peptides, proteins and vitamins) attached to the bilayer surface. Most studies ...have focused on antibody conjugates since procedures for producing highly specific monoclonal antibodies are well established. Antibody conjugated liposomes have recently attracted a great deal of interest, principally because of their potential use as targeted drug delivery systems and in diagnostic applications. A number of methods have been reported for coupling antibodies to the surface of stealth liposomes. The objective of this review is to enumerate various strategies which are employed in the modification and conjugation of antibodies to the surface of stealth liposomes. This review also describes various derivatization techniques of lipids prior and after their use in the preparation of liposomes. The use of single chain variable fragments and affibodies as targeting ligands in the preparation of immunoliposomes is also discussed.
Preparation of PEGylated liposomes and conjugation of intact or derivatized monoclonal antibodies (PEGylated Immunoliposomes) through various functionalized PEG derivatives.
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► To develop and characterize chitosan mucoadhesive microspheres for nasal delivery. ► The Miat
® nasal insufflator was tested for reproducibility of dose delivered. ► The images of ...delivery sequences of powder clouds demonstrated an elongated puff. ► The core of clouds was homogeneous which provide effective distribution pattern.
The aim of the present study was to develop and characterize chitosan mucoadhesive microspheres for nasal delivery. The microspheres were prepared by emulsification-crosslinking method and evaluated for morphology, particle size, swelling index, in vitro mucoadhesion and delivery properties from Miat
® nasal insufflator. The results showed that the microspheres were spherical in shape with smooth surfaces. The particle size of microspheres was found to be dependent on the concentration of the chitosan. The mean particle size was significantly increased when high concentration of chitosan was used. Aqueous to oil phase ratio, stirring rate and dioctyl sodium sulfosuccinate (DOSS) concentration also influenced the particle size distribution of the microspheres. It was found that, as stirring rate was increased, the size of the microspheres was decreased. The volume of glutaraldehyde and crosslinking time had very slight effect on particle size distribution. The % equilibrium water uptake of the microspheres was ranged from 124% to 232% and the mucoadhesive strength from 70.64
±
2.14 to 86.32
±
3.96%. The results of powder delivery from the device showed that, almost entire amount was delivered after three puffs. The images of the delivery sequences of microsphere powder clouds demonstrated that microspheres were delivered forming an elongated puff. The core of the clouds was homogeneous which can be expected to provide effective distribution pattern.
The development of computational methods to assess pathogenicity of pre-messenger RNA splicing variants is critical for diagnosis of human disease. We assessed the capability of eight algorithms, and ...a consensus approach, to prioritize 249 variants of uncertain significance (VUSs) that underwent splicing functional analyses. The capability of algorithms to differentiate VUSs away from the immediate splice site as being 'pathogenic' or 'benign' is likely to have substantial impact on diagnostic testing. We show that SpliceAI is the best single strategy in this regard, but that combined usage of tools using a weighted approach can increase accuracy further. We incorporated prioritization strategies alongside diagnostic testing for rare disorders. We show that 15% of 2783 referred individuals carry rare variants expected to impact splicing that were not initially identified as 'pathogenic' or 'likely pathogenic'; one in five of these cases could lead to new or refined diagnoses.
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► Solid-SNEDDS (S-SNEDDS) prepared by lyophilization using D-mannitol. ► Drug release from SNEDDS was higher than plain drug suspension and pH independent. ► Study showed that, SNEDDS ...have potential to improve the oral bioavailability of ADV.
Adefovir dipivoxil (ADV) is an anti-viral drug having low bioavailability due to low permeability and pH dependent solubility. In this study, self-nanoemulsifying drug delivery systems (SNEDDS) of ADV were developed with the objective of increasing its bioavailability by enhancing its intestinal permeability and minimizing the effect of pH. Preliminary screening was carried out to select oil, surfactant and co-surfactant. Ternary phase diagrams were constructed to identify the area of nanoemulsification. The nanoemulsion system selected from the phase diagram was transformed into solid-SNEDDS (S-SNEDDS) by lyophilization using D-mannitol as cryoprotectant. The formulations were characterized for transmittance, globule size, polydispersity index, zeta potential, cloud point, robustness to dilution, effect of pH and temperature, microscopic properties,
in vitro and
ex vivo drug release parameters. The liquid SNEDDS (L-SNEDDS) showed mean globule size of 110
±
10
nm while mean globule size of 150
±
16
nm was obtained with S-SNEDDS. The formulations were found to be robust to dilution and showed cloud point at 80–85
°C. TEM and SEM studies of nanoemulsion reconstituted from S-SNEDDS demonstrated the spherical shape and size of the globules. Results of DSC and XRD studies confirmed that the drug was incorporated in the S-SNEDDS. No significant difference was observed in the globule size within physiological variations of pH and temperature. The
in vitro and
ex vivo drug release from ADV SNEDDS was found to be significantly higher in comparison to that from plain drug suspension, irrespective of pH. Thus, SNEDDS were found to be instrumental in reducing the effect of pH variability of ADV and improving the release performance of ADV, indicating their potential to improve the oral bioavailability and thus the therapeutic efficacy of ADV.
Albumin is a versatile protein used as a carrier system for cancer therapeutics. As a carrier it can provide tumor specificity, reduce drug related toxicity, maintain therapeutic concentration of the ...active moiety like drug, gene, peptide, protein etc. for long period of time and also reduce drug related toxicities. Apart from cancer therapy, it is also utilized in the imaging and multimodal therapy of cancer. This review highlights the important properties, structure and types of albumin based nanocarriers with regards to their use for cancer targeting. It also provides brief discussion on methods of preparation of these nanocarriers and their surface modification. Applications of albumin nanocarriers for cancer therapy, gene delivery, imaging, phototherapy and multimodal therapy have also been discussed. This review also provides brief discussion about albumin based marketed nano formulations and those under clinical trials.
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•The review describes the use of albumin based nanocarriers in cancer targeting.•Role of different ligands in the surface modification of albumin based nanocarriers.•Albumin based Nanoconjugates like albumin-drug conjugate, albumin-metal conjugate and albumin-polymer conjugates in cancer therapy.•Recent advances of albumin based nanocarriers in multimodal therapy and biomedical field.•Albumin based marketed formulations and clinical trials.
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