Effective Drug Delivery Vehicles Research Articles

Rational Design of Pectin-Chitosan Polyelectrolyte Nanoparticles for Enhanced Temozolomide Delivery in Brain Tumor Therapy.

Conventional chemotherapeutic approaches currently used for brain tumor treatment have low efficiency in targeted drug delivery and often have non-target toxicity. Development of stable and effective drug delivery vehicles for the most incurable diseases is one of the urgent biomedical challenges. We have developed polymer nanoparticles (NPs) with improved temozolomide (TMZ) delivery for promising brain tumor therapy, performing a rational design of polyelectrolyte complexes of oppositely charged polysaccharides of cationic chitosan and anionic pectin. The NPs' diameter (30 to 330 nm) and zeta-potential (-29 to 73 mV) varied according to the initial mass ratios of the biopolymers. The evaluation of nanomechanical parameters of native NPs demonstrated changes in Young's modulus from 58 to 234 kPa and adhesion from -0.3 to -3.57 pN. Possible mechanisms of NPs' formation preliminary based on ionic interactions between ionogenic functional groups were proposed by IR spectroscopy and dynamic rheology. The study of the parameters and kinetics of TMZ sorption made it possible to identify compounds that most effectively immobilize and release the active substance in model liquids that simulate the internal environment of the body. A polyelectrolyte carrier based on an equal ratio of pectin-chitosan (0.1% by weight) was selected as the most effective for the delivery of TMZ among a series of obtained NPs, which indicates a promising approach to the treatment of brain tumors.

The impact of cationic/anionic ratio on the physicochemical aspects of catanionic niosomes as a promising carrier for anticancer drugs

BackgroundNiosomes are adaptable nanocarriers for the delivery and controlled release of anticancer drugs. The addition of ionic surfactants could easily functionalize these carriers. Catanionic niosomes that are comprised of cationic and anionic surfactants are effective drug-delivery vehicles. Here, we aim to evaluate the impact of the cationic/anionic ratio on the noisome characteristics. MethodsA novel approach utilizing molecular modeling was utilized to analyze some characteristics of catanionic niosomes, showing great potential as a vehicle for anticancer drugs. The nonionic surfactant SPAN60, along with cholesterol as the stabilizer, was utilized in the study. Moreover, CTAB and SDS were used as positively and negatively charged surfactants, respectively. An FDA-approved c-Met inhibitor, cabozantinib, was selected as the drug. Several significant parameters associated with the cabozantinib molecule and its properties within the bilayer like hydrogen bonding, total energy, radius of gyration (Rgyr), diffusion coefficient, and radial distribution function (RDF). ResultsThe findings suggest that the cabozantinib’s hydrogen bonding plays a vital role in the drug’s movement through the bilayer. The CTAB-rich niosomes showed a higher number of hydrogen bonds compared to the SDS-rich formulations. The diffusion coefficient was in agreement with the number of H-bonding, and this value increased from 3.12 × 10-12 (m2/s) in CTAB-rich niosome to 7.66 × 10-12 (m2/s) in SDS-rich niosime. ConclusionThe total binding energy between the drug and bilayer components can control drug release. The computational approach could sufficiently describe the influence of cationic/anionic molar ratios on the bilayer features, and the characteristics of catanionic niosomes could be easily adjusted for the controlled release of anticancer drugs.

Lipids Extracted from Mycobacterial Membrane and Enveloped PLGA Nanoparticles for Encapsulating Antibacterial Drugs Elicit Synergistic Antimicrobial Response against Mycobacteria.

Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen's cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen's cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.

Biotechnological Effects of Advanced Smart-Bile Acid Cyclodextrin-Based Nanogels for Ear Delivery and Treatment of Hearing Loss.

Inner ear delivery requires safe and effective drug delivery vehicles incorporating high-viscosity formulations with permeation enhancers. This study designs novel thermoresponsive-smart polymer-bile acid and cyclodextrin-based nanogels for inner ear delivery. Nanogels are examined for their rheological and physical properties. The biocompatibility studies will be assessed on auditory and macrophage cell lines by investigating the impact of nanogels on cellular viability, mitochondrial respiration, glycolysis, intracellular oxidative stress, inflammatory profile, and macrophage polarization. Novel ther nanogels based on bile acid and beta-cyclodextrin show preserved porous nanogels' inner structure, exhibit non-Newtonian, shear-thinning fluid behavior, have fast gelation at 37°C and minimal albumin adsorption on the surface. The nanogels have minimal impact on cellular viability, mitochondrial respiration, glycolysis, intracellular oxidative stress, and inflammatory profile of the auditory cell line House Ear Institute-Organ of Corti 1 after 24h incubation. Nanogel exposure of 24h to macrophage cell line RAW264.7 leads to decreased viability, mitochondrial dysfunction, and increased intracellular ROS and inflammatory cytokines. However, polarization changes from M2 anti-inflammatory to M1 pro-inflammatory macrophages are minimal, and inflammatory products of RAW264.7 macrophages do not overly disrupt the survivability of HEI-OC1 cells. Based on these results, thermoresponsive bile acid and cyclodextrin nanogels can be potential drug delivery vehicles for inner ear drug delivery.

Deep eutectic solvent based self-healable, stretchable and injectable eutectogels: A versatile platform for breast cancer treatment

Recent focus is on developing cancer treatments that overcome challenges of high-dose chemotherapy, providing improved safety, effectiveness, and site-specific targeting through responsive mechanisms. In our quest for an advanced drug delivery vehicle, herein we have developed a self-healable and injectable polymeric eutectogels that responds to intracellular biological stimuli i.e., pH and temperature. The eutectogels made through interacting imidazolium based deep eutectic solvents with polyvinyl alcohol serve as a local drug delivery system for cancer therapeutics, releasing the anti-cancer drug 5-fluorouracil (5-FU) to the targeted site through intracellular pH, i.e. pH 5.0. Rheology experiments showed strong mechanical strength (>7.3 % strain) for the studied eutectogels that have hierarchical and porous 3D network morphology formed by thick fibers. It exhibits crucial qualities- swelling, injectability, and self-healing- essential for an effective drug delivery vehicle. Additionally, eutectogels demonstrates outstanding biocompatibility, with hemolysis below 2 %, ensuring blood compatibility and sustained viability in HaCaT cells. Leveraging these properties, 5-FU-loaded eutectogels were studied for in vitro cytotoxicity (MCF-7 and HeLa) and drug release that revealed that the eutectogels can be used for targeted delivery under physiological conditions and can more efficiently kill cancerous cells.

Innovative utilization of cell membrane‐coated nanoparticles in precision cancer therapy

AbstractCell membrane‐coated nanoparticles (CMNPs) have recently emerged as a promising platform for cancer therapy. By encapsulating therapeutic agents within a cell membrane‐derived coating, these nanoparticles combine the advantages of synthetic nanoparticles and natural cell membranes. This review provides a comprehensive overview of the recent advancements in utilizing CMNPs as effective drug delivery vehicles for cancer therapy. The synthesis and fabrication methods of CMNPs are comprehensively discussed. Various techniques, such as extrusion, sonication, and self‐assembly, are employed to coat synthetic nanoparticles with cell membranes derived from different cell types. The cell membrane coating enables biocompatibility, reducing the risk of an immune response and enhancing the stability of the nanoparticles in the bloodstream. Moreover, functionalization strategies for CMNPs, primarily chemical modification, genetic engineering, and external stimuli, are highlighted. The presence of specific cell surface markers on the coated membrane allows targeted drug delivery to cancer cells and maximizes therapeutic efficacy. Preclinical studies utilizing CMNPs for cancer therapy demonstrated the successful delivery of various therapeutic agents, such as chemotherapeutic drugs, nucleic acids, and immunotherapeutic agents, using CMNPs. Furthermore, the article explores the future directions and challenges of this technology while offering insights into its clinical potential.

Designing Gold Nanoparticles for Precise Glioma Treatment: Challenges and Alternatives.

Glioblastoma multiforme (GBM) is a glioma and the most aggressive type of brain tumor with a dismal average survival time, despite the standard of care. One promising alternative therapy is boron neutron capture therapy (BNCT), which is a noninvasive therapy for treating locally invasive malignant tumors, such as glioma. BNCT involves boron-10 isotope capturing neutrons to form boron-11, which then releases radiation directly into tumor cells with minimal damage to healthy tissues. This therapy lacks clinically approved targeted blood-brain-barrier-permeating delivery vehicles for the central nervous system (CNS) entry of therapeutic boron-10. Gold nanoparticles (GNPs) are selective and effective drug-delivery vehicles because of their desirable properties, facile synthesis, and biocompatibility. This review discusses biomedical/therapeutic applications of GNPs as a drug delivery vehicle, with an emphasis on their potential for carrying therapeutic drugs, imaging agents, and GBM-targeting antibodies/peptides for treating glioma. The constraints of GNP therapeutic efficacy and biosafety are discussed.

In Vitro and In Vivo Evaluation of the Pathology and Safety Aspects of Three- and Four-Way Junction RNA Nanoparticles.

RNA therapeutics has advanced into the third milestone in pharmaceutical drug development, following chemical and protein therapeutics. RNA itself can serve as therapeutics, carriers, regulators, or substrates in drug development. Due to RNA's motile, dynamic, and deformable properties, RNA nanoparticles have demonstrated spontaneous targeting and accumulation in cancer vasculature and fast excretion through the kidney glomerulus to urine to prevent possible interactions with healthy organs. Furthermore, the negatively charged phosphate backbone of RNA results in general repulsion from negatively charged lipid cell membranes for further avoidance of vital organs. Thus, RNA nanoparticles can spontaneously enrich tumor vasculature and efficiently enter tumor cells via specific targeting, while those not entering the tumor tissue will clear from the body quickly. These favorable parameters have led to the expectation that RNA has low or little toxicity. RNA nanoparticles have been well characterized for their anticancer efficacy; however, little detail on RNA nanoparticle pathology and safety is known. Here, we report the in vitro and in vivo assessment of the pathology and safety aspects of different RNA nanoparticles including RNA three-way junction (3WJ) harboring 2'-F modified pyrimidine, folic acid, and Survivin siRNA, as well as the RNA four-way junction (4WJ) harboring 2'-F modified pyrimidine and 24 copies of SN38. Both animal models and patient serum were investigated. In vitro studies include hemolysis, platelet aggregation, complement activation, plasma coagulation, and interferon induction. In vivo studies include hematoxylin and eosin (H&E) staining, hematological and biochemical analysis as the serum profiling, and animal organ weight study. No significant toxicity, side effect, or immune responses were detected during the extensive safety evaluations of RNA nanoparticles. These results further complement previous cancer inhibition studies and demonstrate RNA nanoparticles as an effective and safe drug delivery vehicle for future clinical translations.

Characterization of Graft Copolymers Synthesized from p-Aminosalicylate Functionalized Monomeric Choline Ionic Liquid.

An ionic liquid based on the monomeric choline, specifically [2-(methacryloyloxy)ethyl]-trimethylammonium chloride (TMAMA), underwent biofunctionalization through an ion exchange reaction with the model drug anion: p-aminosalicylate (PAS), a primary antibiotic for tuberculosis treatment. This modified biocompatible IL monomer (TMAMA/PAS) was subsequently copolymerized with methyl methacrylate (MMA) to directly synthesize the well-defined graft conjugates with regulated content of ionic fraction with PAS anions (up to 49%), acting as drug delivery systems. The length of the polymeric side chains was assessed by the monomer conversions, yielding a degree of polymerization ranging from 12 to 89. The density of side chains was controlled by "grafting from" using the multifunctional macroinitiators. In vitro drug release, triggered by the ion exchange between the pharmaceutical and phosphate anions in a PBS medium, occurred in the range of 71-100% (2.8-9.8 μg/mL). Owing to significant drug content and consistent release profiles, these particular graft copolymers, derived from biomodified IL monomers with ionically attached pharmaceutical PAS in the side chains, are recognized as potentially effective drug delivery vehicles.

Biocompatible Snowman-like Dimer Nanoparticles for Improved Cellular Uptake in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive types of human cancers. Although paclitaxel (PTX) was proven to exert potent anti-tumor effects against ICC, the delivery of PTX is still challenging due to its hydrophobic property. Nanoparticle (NP)-based carriers have been proven to be effective drug delivery vehicles. Among their physicochemical properties, the shape of NPs plays a crucial role in their performance of cellular internalization and thus anti-tumor efficacy of loaded drugs. In this study, dumbbell-like and snowman-like dimer NPs, composed of a polylactic acid (PLA) bulb and a shellac bulb, were designed and prepared as drug nanocarriers to enhance the efficiency of cellular uptake and anti-tumor performance. PLA/shellac dimer NPs prepared through rapid solvent exchange and controlled co-precipitation are biocompatible and their shape could flexibly be tuned by adjusting the concentration ratio of shellac to PLA. Drug-loaded snowman-like PLA/shellac dimer NPs with a sharp shape exhibit the highest cellular uptake and best cell-killing ability against cancer cells in an in vitro ICC model over traditional spherical NPs and dumbbell-like dimer NPs, as proven with the measurements of flow cytometry, fluorescent confocal microscopy, and the CCK8 assay. The underlying mechanism may be attributed to the lower surface energy required for the smaller bulbs of snowman-like PLA/shellac dimer NPs to make the initial contact with the cell membrane, which facilitates the subsequent penetration through the cellular membrane. Therefore, these dimer NPs provide a versatile platform to tune the shape of NPs and develop innovative drug nanocarriers that hold great promise to enhance cellular uptake and therapeutic efficacy.

M6P-modified solid lipid nanoparticles loaded with matrine for the treatment of fibrotic liver

Liver fibrosis is a key pathological process shared by the progression of various chronic liver diseases. Treatment of liver fibrosis can effectively block the occurrence and development of hepatic cirrhosis or even carcinoma. Currently, there is no effective drug delivery vehicle for curing liver fibrosis. In this study, we designed matrine (MT)-loaded mannose 6-phosphate (M6P) modified human serum albumin (HSA) conjugated solid lipid nanoparticles (SLN), named M6P-HSA-MT-SLN for treatment of hepatic fibrosis. We demonstrated that M6P-HSA-MT-SLN exhibited controlled and sustained release properties and good stability over 7 days. The drug release experiments showed that M6P-HSA-MT-SLN exhibited slow and controlled drug release characteristics. In addition, M6P-HSA-MT-SLN showed a significant targeted ability to fibrotic liver. Importantly, in vivo studies indicated that M6P-HSA-MT-SLN could significantly improve histopathological morphology and inhibit the fibrotic phenotype. In addition, in vivo experiments demonstrate that M6P-HSA-MT-SLN could reduce the expression of fibrosis markers and alleviate the damage of liver structure. Hence, the M6P-HSA-MT-SLN provide a promising strategy to deliver therapeutic agents to fibrotic liver to prevent liver fibrosis.

Immobilization of saponin on chitosan Milli-particles for Type II diabetic treatment

Type II diabetes mellitus (T2DM) has caused an adverse impact on the health of more than a tenth of the Malaysian population. Saponin is a traditional herbal extract found to be effective in treating T2DM with milder toxicity, which makes it a good alternative to conventional anti-diabetic drugs with side effects. This research develops an effective drug delivery vehicle to transport the saponin extract via chitosan milli-particles (CPs) for targeted release in the digestive system. Saponin was loaded onto the CPs via electrostatic interaction following the surface charge alteration of the CPs. Swelling tests and an in vitro study based on simulated gastrointestinal conditions were conducted on the saponin-immobilized CPs (SICPs). The release of saponin from its carrier is attributed to Fickian diffusion and swelling of the chitosan milli-particle matrix at pH 1.2 and 6.8.

Preparation of chitosan nanoparticles for simultaneous drug delivery of dacarbazine and enoxaparin in melanoma

The aim of this study was to investigate the anti-melanoma and anti-angiogenic effects of enoxaparin surface-coated dacarbazine-loaded chitosan nanoparticles (Enox-Dac-Chi NPs). The prepared Enox-Dac-Chi NPs had a particle size of 367.95 ± 1.84 nm, zeta potential of −7.12 ± 0.25 mV, efficiency of drug loading (DL%) of 73.90 ± 3.84 %, and attached enoxaparin percentage of 98.53 ± 0.96 %. Both drugs had extended-release profiles and approximately 96 % of enoxaparin and 67 % dacarbazine were released within 8 h. The Enox-Dac-Chi NPs with IC50 of 59.60 ± 1.25 μg/ml were the most cytotoxic against melanoma cancer cells compared with chitosan nanoparticles containing only dacarbazine (Dac-Chi NPs) and free dacarbazine. There was no significant difference between the cellular uptake of Chi NPs and enoxaparin coated Chi NPs (Enox-Chi NPs) in B16F10 cells. Enox-Chi NPs with an average anti-angiogenic score of 1.75 ± 0.125 had more anti-angiogenic effect than enoxaparin. The results showed that simultaneous delivery of dacarbazine and enoxaparin by chitosan nanoparticles can enhance the anti-melanoma effect of dacarbazine. Additionally, enoxaparin can prevent the melanoma metastasis by its anti-angiogenic activity. Thus, the designed nanoparticles can be introduced as effective drug delivery vehicles for the treatment and prevention of metastatic melanoma.

DEVELOPMENT, CHARACTERIZATION AND ANTIBACTERIAL PROPERTIES OF SILVER NANOPARTICLES LOADED SODIUM ALGINATE/XANTHAN GUM MICROBEADS FOR DRUG DELIVERY APPLICATIONS

Objective: The aim of this study is to create pH-responsive drug carriers, which are useful because they have the potential to improve treatment efficacy by controlling the release rate of ofloxacin from the polymer matrix. Methods: In the first step, silver nanoparticles (Ag NPs) were synthesized from silver nitrate using leaf extract of phyllanthus urinaria L as a reducing agent. In the second step, Ag-NPs-loaded polymeric microbeads were synthesized using sodium alginate (SA) and xanthan gum (XG) for controlled release of ofloxacin (OFLX). The developed microbeads were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (X-RD), transition electron microscopy (TEM), Selected Area Electron Diffraction (SAED), and scanning electron microscopy (SEM). Swelling and in vitro release studies were performed at pH 2.0 and 7.4 at 37 °C. The in vitro antibacterial activity of microbeads were tested against S. mutans, K. pneumoniae, and B. subtilis. The release kinetics and mechanism were analyzed by fitting the release data into different kinetic models and the korsmeyer-peppas equation. Results: FTIR confirms the generation of silver nanoparticle and also the generation of polymeric microbeads. SEM studies reveal the developed microbeads are spherical in shape with rough surfaces. TEM studies reveal the size of 20-40 nm. XRD analysis reveals the molecular dispersion of DOX and the presence of silver nanoparticles in the polymeric matrix. Investigations of in vitro release and swelling studies show that the developed microbeads are relatively suitable for intestinal drug delivery because higher release rate was observed at pH 7.4. The developed microbead follows non-Fickian diffusion drug release mechanism. The created samples exhibited antimicrobial activity against S. mutans, K. pneumoniae, and B. subtilis. Conclusion: The results indicate that microbeads containing OFLX and silver nanoparticles are effective drug-delivery vehicles. A further warrant is required for the use of manufactured microbeads in drug delivery applications.

Influence of urea/glucose on the mixed micellization behavior of amitriptyline hydrochloride and 1-hexadecyl-3-methylimidazolium chloride (ionic liquid) mixtures: An experimental and theoretical investigation

Mixtures of an antidepressant drug, amitriptyline hydrochloride (AMT), and ionic liquid, 1-hexadecyl-3-methylimidazolium chloride (HMICl), were investigated by tensiometry at a temperature of 298.15 K with diverse mole fraction (α1) of HMICl to determine the association, surface, and thermodynamic properties. Fourier transform infrared (FTIR) and UV–visible spectroscopy were also used to estimate the interactions between AMT and HMICl. AMT can treat depression, anxiety, and other mental illnesses. Imidazolium-based surface-active ionic liquids are ideal for biomedical uses because of their unique physicochemical properties. The interaction between AMT and HMICl was also examined using non-aqueous solvent systems (500 mmol·kg−1 urea and 250 mmol·kg−1 glucose). The ideal cmc (cmcid) measured for the mixed system (AMT + HMICl) tensiometry was notably smaller than the critical micelle concentration (cmc). As a result, AMT and HMICl interact fairly well, and interaction also increased when the α1 of HMICl increased. The cmc values for pure and mixed solutions in urea were higher than those in aqueous, while in glucose, they were lower. Hypothetical models, including those of Clint, Motomura, Rubingh, and Rosen, have been used to determine the association, interfacial, and thermodynamic properties. For each constituent, the activity coefficients were consistently < 1 for micellar along with interface, exhibiting the intermolecular interactions amongst constituents as well as nonideal behavior. The excess free energy was negative in each case, implying that mixed micelles and monolayers have higher stability than micelles and monolayers of single components. The direct interaction of AMT and HMICl was also characterized by FTIR and UV–visible analysis, similar to the tensiometric method. In summary, the ionic liquid HMICl may be an effective drug delivery vehicle.

Hydroxyapatite microbeads containing BMP-2 and quercetin fabricated via electrostatic spraying to encourage bone regeneration

BackgroundHydroxyapatite (HAp) possesses osteoconductive properties, and its granular form can serve as an effective drug delivery vehicle for bone regeneration. Quercetin (Qct), a plant-derived bioflavonoid, is known to promote bone regeneration; however, its comparative and synergistic effects with the commonly used bone morphogenetic protein-2 (BMP-2) have not been investigated.MethodsWe examined the characteristics of newly formed HAp microbeads using an electrostatic spraying method and analyzed the in vitro release pattern and osteogenic potential of ceramic granules containing Qct, BMP-2, and both. In addition, HAp microbeads were transplanted into a rat critical-sized calvarial defect and the osteogenic capacity was assessed in vivo.ResultsThe manufactured beads had a microscale size of less than 200 μm, a narrow size distribution, and a rough surface. The alkaline phosphatase (ALP) activity of osteoblast-like cells cultured with the BMP-2-and-Qct-loaded HAp was significantly higher than that of either Qct- or BMP-2-loaded HAp groups. The mRNA levels of osteogenic marker genes such as ALP and runt-related transcription factor 2 were found to be upregulated in the HAp/BMP-2/Qct group compared to the other groups. In micro-computed tomographic analysis, the amount of newly formed bone and bone surface area within the defect was significantly higher in the HAp/BMP-2/Qct group, followed by the HAp/BMP-2 and HAp/Qct groups, which is consistent with the histomorphometrical results.ConclusionsThese results imply that electrostatic spraying can be an efficient strategy to produce homogenous ceramic granules and that the BMP-2-and-Qct-loaded HAp microbeads can serve as effective implants for bone defect healing.

Bioactive potential of morin loaded mesoporous silica nanoparticles: A nobel and efficient antioxidant, antidiabetic and biocompatible abilities in in-silico, in-vitro, and in-vivo models

Developing a delivery system has become crucial in engineering cutting-edge next-generation theranostic approaches. Therefore, in the present research work, a customized Mesoporous silica nanoparticle (MSiNPs) was designed by adapting the Stöber method with silane polymerization for Morin (MO) adsorption. The average size of MSiNPs was 50–130 nm as measured by TEM, while FE-SEM revealed a spherical surface shape. According to Raman and FTIR spectra, while the synthesis of MSiNPs, CTAB (a surfactant) was eliminated from MSiNPs, silane was functionalized, and with a loading efficiency of 10.28 ± 0.22%, MO was adsorbed. Molecular docking was used to perform in-silico studies to investigate the interaction of native MO with antidiabetic and antioxidant enzymes. Furthermore, the antioxidant and antidiabetic effects of both MO adsorbed MSiNPs, and native MO were examined in vitro, with the former showing promise even at lower concentrations than the latter. The cell survival experiment on Mouse macrophages RAW 264.7 and HCT cells revealed that MO adsorbed MSiNPs were nontoxic up to 15 μg/ml. The acute toxicity of different concentrations of MO adsorbed MSiNPs was also conducted in an in vivo model zebrafish (Danio rerio), where the study was conducted for about 96 h and evaluated for histological significance. The findings described above revealed that the MSiNPs were electrochemically, structurally, and thermally stable and MO adsorbed MSiNPs were nontoxic and biocompatible, implying that it might be an effective drug delivery vehicle for MO in the future. Moreover, in coming times, this nano-delivery system with effective biodistribution of the adsorbed MO could be explored as an antidiabetic and anti-cancer agent.

An oral delivery vehicle based on konjac glucomannan acetate targeting the colon for inflammatory bowel disease therapy.

Orally administered colon-targeted delivery vehicles are of major importance in the treatment of inflammatory bowel disease (IBD). However, it remains a challenge to maintain the integrity of such delivery vehicles during treatment, particularly in the gastric environment, which may cause untimely drug release before reaching the targeted colon. Herein, an oral colon-targeted drug delivery system (OCDDS) based on acetylated konjac glucomannan (AceKGM) has been developed in this work, which accomplishes colonic localization release and targets local inflammatory macrophages. The AceKGM nanoparticle-loading curcumin (Cur) was successfully fabricated by emulsion solvent evaporation techniques. DLS, AFM, and SEM were used in order to evaluate the nanoparticles' diameter as well as their in vitro drug release profile, and reactive oxygen species (ROS) scavenging results showed that the OCDDS considerably retained the activity of Cur treated with simulated gastric fluid (SGF) and controllably released in simulated intestinal fluid (SIF). In addition, the adhesion experiment results indicated that the nanoparticle could accumulate on the colonic macrophages. Evaluations in colitis mice showed that the treatment significantly alleviated the symptoms of colitis by decreasing the local level of myeloperoxidase (MPO) and the disease activity index (DAI) score in mice. In summary, the results of our research demonstrate that Cur-AceKGM nanoparticles exhibit significantly improved therapeutic efficacy compared to orally administered free Cur and can be developed as an effective drug delivery vehicle for IBD treatment.

Gold Nanoparticle-Based Resuscitation of Cefoxitin against Clinical Pathogens: A Nano-Antibiotic Strategy to Overcome Resistance.

Gold nanoparticles have gained popularity as an effective drug delivery vehicle due to their unique features. In fact, antibiotics transported via gold nanoparticles have significantly enhanced their potency in the recent past. The present study used an approach to synthesize gold nanoparticles in one step with the help of cefoxitin antibiotic as a reducing and stabilizing agent. Cefoxitin is a second-generation cephalosporin that loses its potential due to modification in the porins (ompK35 and ompK36) of Gram-negative pathogens. Thus, the present study has developed an idea to revive the potential of cefoxitin against clinical Gram-negative pathogens, i.e., Escherichia coli and Klebsiella pneumoniae, via applying gold nanoparticles as a delivery tool. Prior to antibacterial activity, characterization of cefoxitin–gold nanoparticles was performed via UV–visible spectrophotometry, dynamic light scattering, and electron microscopy. A characteristic UV–visible scan peak for gold nanoparticles was observed at 518 nm, ζ potential was estimated as −23.6 ± 1.6, and TEM estimated the size in the range of 2–12 nm. Moreover, cefoxitin loading efficiency on gold nanoparticles was calculated to be 71.92%. The antibacterial assay revealed that cefoxitin, after loading onto the gold nanoparticles, become potent against cefoxitin-resistant E. coli and K. pneumoniae, and their MIC50 values were estimated as 1.5 μg/mL and 2.5 μg/mL, respectively. Here, gold nanoparticles effectively deliver cefoxitin to the resistant pathogens, and convert it from unresponsive to a potent antibiotic. However, to obtain some convincing conclusions on the human relevance, their fate and toxicity need to be evaluated.

Decalepis hamiltonii derived gold nanoparticles and photodynamic cytotoxic evaluation on skin melanoma (B16F10) cells as an effective drug delivery vehicle

The present work describes the use of gold nanoparticles as an efficient drug delivery vehicle to target skin melanoma cells B16F10 by photodynamic cancer therapy. For the first time, gold nanoparticles were synthesized from medicinally important plant Decalepis hamiltonii. The nanoparticles were further conjugated with an anticancer drug 5-aminolevulinic acid (5-ALA) and subsequently activating the photosensitizer molecule protoporphyrin IX (PpIX) through irradiation which resulted in the formation of reactive oxygen species. The roots of Decalepis hamiltonii was used for the synthesis of gold nanoparticles by a simple technique of reduction reaction and the morphology like size, shape, charge were evaluated using SEM (Scanning Electron Microscopy), DLS (Dynamic Light Scattering) and Zeta potential analysis. The cytotoxicity of nanoparticles were tested on RBCs and buccal cells which showed there was negligible damage to the cells. The photodynamic therapy was tested on skin melanoma cells and the results were compared with the standard drug 5-ALA and production of ROS molecules was evaluated using 2,7 dichlorofluorescein-diacetate (DCFH-DA) probe. The results indicated that the gold-5ALA conjugates had a deleterious effect on cancer cells specially after activation of protoporphyrin IX and showed a two fold increase in cytotoxic level post irradiation. Interestingly, the gold nanoparticles and conjugates which showed high cytotoxicity against cancer cells had no significant effect on normal RBCs and buccal cells indicating there was a specific target on cancer cells.