In-vivo Studies Research Articles

A comprehensive review of the application of 3D-bioprinting in chronic wound management.

Chronic wounds require more sophisticated care than standard wound care because they are becoming more severe as a result of diseases like diabetes. By resolving shortcomings in existing methods, 3D-bioprinting offers a viable path toward personalized, mechanically strong, and cell-stimulating wound dressings. This review highlights the drawbacks of traditional approaches while navigating the difficulties of managing chronic wounds. The conversation revolves around employing natural biomaterials for customized dressings, with a particular emphasis on 3D-bioprinting. A thorough understanding of the uses of 3D-printed dressings in a range of chronic wound scenarios is provided by insights into recent research and patents. The expert view recognizes wounds as a historical human ailment and emphasizes the growing difficulties and expenses related to wound treatment. The expert acknowledges that 3D printing is revolutionary, but also points out that it is still in its infancy and has the potential to enhance mass production rather than replace it. The review highlights the benefits of 3D printing for wound dressings by providing instances of smart materials that improve treatment results by stimulating angiogenesis, reducing pain, and targeting particular enzymes. The expert advises taking action to convert the technology's prospective advantages into real benefits for patients, even in the face of resistance to change in the healthcare industry. It is believed that the increasing evidence from in-vivo studies is promising and represents a positive change in the treatment of chronic wounds toward sophisticated 3D-printed dressings.

A framework for integrating evidence to assess hazards and risk.

To accurately characterize human health hazards, human, animal, and mechanistic data must be integrated and the relevance to the research question of all three lines of evidence must be considered. Mechanistic data are often critical to the full integration of animal and human data and to characterizing relevance and uncertainty. This novel evidence integration framework (EIF) provides a method for synthesizing data from comprehensive, systematic, quality-based assessments of the epidemiological and toxicological literature, including invivo and invitro mechanistic studies. It organizes data according to both the observed human health effects and the mechanism of action of the chemical, providing a method to support evidence synthesis. The disease-based component uses the evidence of human health outcomes studied in the best quality epidemiological literature to organize the toxicological data according to authors' stated purpose, with the pathophysiology of the disease determining the potential relevance of the toxicological data. The mechanism-based component organizes the data based on the proposed mechanisms of effect and data supporting events leading to each endpoint, with the epidemiological data potentially providing corroborating information. The EIF includes a method to cross-classify and describe the concordance of the data, and to characterize its uncertainty. At times, the two methods of organizing the data may lead to different conclusions. This facilitates identification of knowledge gaps and shows the impact of uncertainties on the strength of causal inference.

Novel Small Molecule, UTS-1401, as a Radioprotector for Total-Body Irradiation.

We report on a new radioprotector, UTS-1401, a small molecule that was synthesized (by one of us, JS) and evaluated here for its radioprotective effect against total-body irradiation (TBI). Female and male NIH Swiss mice were subjected to TBI at doses of 6.5, 7.5 and 8.5 Gy either with or without a 24 h pretreatment of UTS-1401 given ip and observed for 30 days. Survival rates were significantly increased when mice were treated with UTS-1401 compared to those not treated. The radioprotective effect of UTS-1401 was drug-dose dependent for male mice exposed to 8.5 Gy TBI with 150 mg/kg of UTS-1401 as the optimal dose. The radioprotective effect of UTS-1401 on female mice exposed to 8.5 Gy TBI was observed at 50, 100, and 150 mg/kg, with no dose response relationship noted. Female mice were more radioresistant than male mice with LD50/30 values of 7.8 Gy vs. 6.8 Gy, respectively. Weight changes after UTS-1401 alone showed a significant body weight increase at 150 mg/kg. Both the ip and iv route for UTS-1401 were similarly effective for male mice exposed to 8 Gy TBI. Further analysis using an endogenous spleen colony assay demonstrated that pretreatment of UTS-1401 for up to 72h prior to TBI protected both spleen weight and hematopoietic stem cells with a treated/untreated ratio between 2.0 and 3.2 for the latter for times between 0.5 h and 72 h. A separate invivo study showed that pretreatment of UTS-1401 protected bone marrow CFU-GM for mice exposed to TBI. In summary, UTS-1401 is a promising small-molecule radioprotective agent as demonstrated by whole animal, hematopoietic stem cell and bone marrow myeloid progenitor cell survival.

Potential antivirulence activity of sub-inhibitory concentrations of ciprofloxacin against Proteus mirabilis isolates: an in-vitro and in-vivo study.

Proteus mirabilis is a significant nosocomial pathogen that is frequently associated with a wide range ofinfections, necessitating heightened attention to mitigate potential health risks. Hence, this study was performed to investigate the impact of sub-minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) on Proteus mirabilis clinical isolates. The sub-MICs of CIP were selected using the growth curve approach. The untreated and treated isolates with sub-MICs of CIP were assessed for their biofilm development, motilities on agar, and other virulence factors. The cell morphology of untreated and treated isolates with sub-MIC of CIP was explored using electron microscope. Moreover, the expression levels of the virulence genes in isolates were measured using quantitative real-time PCR. Data revealed that sub-MICs of CIP significantly (p < 0.05), in a concentration-dependent manner, inhibited biofilm formation and other virulence factors in the selected isolates. Electron microscope analysis showed cell enlargement and various abnormalities in the cell wall and membrane integrity. Sub-MICs of CIP exhibited inhibition of virulence and alterations in morphological integrity against P. mirabilis isolates.

In Vivo Study of Moringa oleifera Seed Extracts as Potential Sources of Neuroprotection against Rotenone-Induced Neurotoxicity

In Vivo Study of Moringa oleifera Seed Extracts as Potential Sources of Neuroprotection against Rotenone-Induced Neurotoxicity

Biological evaluation of novel phosphorylated pullulan-based calcium hydroxide formulations as direct pulp capping materials: An invivo study on a rat model.

Calcium hydroxide (CH) has been considered as a direct pulp capping materials (DPC) for the last decades despite having some limitations. Phosphorylate pullulan (PPL) incorporated with CH (CHPPL) is a novel biomaterial that was introduced as a promising DPC material. Thus, the aim of the study was to evaluate the inflammatory response and mineralized tissue formation (MTF) ability of PPL-based CH formulations on rat molars after DPC. This study consisted of six groups: CH with 1% PPL (CHPPL-1); 3% PPL (CHPPL-3); 5% PPL (CHPPL-5); Dycal and NEX MTA Cement (N-MTA) as the positive control, and no capping materials (NC). One hundred twenty maxillary first molar cavities were prepared on Wistar rats. After capping, all the cavities were restored with 4-META/MMA-TBB resin and pulpal responses were evaluated at days 1, 7, and 28. Kruskal-Wallis followed by Mann-Whitney U-test was performed with a significance level of 0.05. Immunohistochemical expression of IL-6, Nestin, and DMP-1 was observed. At day 1, CHPPL-1, N-MTA, and Dycal exhibited no to mild inflammation, whilst CHPPL-3, CHPPL-5, and NC showed mild to moderate inflammation, and the results were significantly different (p < .05). At day 7, mild to moderate inflammation was observed in CHPPL-1, N-MTA, and Dycal, whereas CHPPL-3, CHPPL-5, and NC exhibited moderate to severe inflammation. Significant differences were observed between CHPPL-1 and N-MTA with NC (p < .05), CHPPL-1 and CHPPL-3 with CHPPL-5 and Dycal (p < .05), and CHPPL-3 with N-MTA (p < .05). A thin layer of mineralized tissue formation (MTF) was observed in all groups. At day 28, CHPPL-1, Dycal, and N-MTA showed no to mild inflammation, whilst CHPPL-3, CHPPL-5, and NC exhibited mild to severe inflammation, and statistically significant difference was detected (p < .05). CHPPL-1, Dycal, and N-MTA exhibited continuous MTF, whilst CHPPL-3, CHPPL-5, and NC had thicker and interrupted MTF. Significant differences were observed between CHPPL-1, CHPPL-3, and N-MTA with NC group (p < .05). Variable expressions of IL-6, Nestin, and DMP-1 indicated differences in the materials' impact on odontoblast-like cell formation and tissue mineralization. These findings suggest that CHPPL-1 has the potential to minimize pulpal inflammation and promote MTF and had similar efficacy as MTA cement.

Optimisation and in-vivo evaluation of extracted Karanjin loaded liposomal topical formulation for treatment of psoriasis in tape-stripped mouse model

Aim The present work is focus on development of anti-psoriasis activity of Karanjin (isolated from Pongamia pinnata seed oil) loaded liposome based lotion for enhancement of skin permeation and retention. Method Karanjin was isolated using liquid-liquid extraction method and characterised by HPLC analysis and partition coefficient. Further, isolated Karanjin was loaded into liposomes using thin-film hydration technique and optimised by Box-Behnken design. Selected optimised batch was characterised their mean diameter, PDI, zeta potential, and entrapment efficiency, morphology (by TEM), FTIR and ex-vivo skin retention. Additionally, Karanjin loaded liposomes were formulated into lotion and characterise their rheological, spreadability, texture, ex-vivo skin permeation & retention, stability and anti-psoriatic activity in mouse tail model. Result The yield of Karanjin from seed oil was 0.1% w/v and have lipophilic nature. The optimised liposomal formulation showed 195 ± 1.8 nm mean diameter, 0.271 ± 0.02 PDI, −27.0 ± 2.1 mV zeta potential and 61.97 ± 2.5% EE. TEM image revel the spherical shap of liposome surrounded by single phospholipid bilayer and no interection between drug and excipients. Further, lotion was prepared by 0.1% w/v carbopol and found to 615 mPa.sec viscosity, good thixotropic behaviour, spreadability and texture. There was 22.44% increase in drug permeation for Karanjin loaded liposomal lotion compared to pure Karanjin lotion, confirm by ex-vivo permeation and retention. While, in-vivo study revel the liposomal lotion of Karanjin was found to have 16.09% higher drug activity then 5% w/w conventional Karanjin lotion. Conclusion Karanjin loaded liposomal lotion have an effective anti-psoriatic agent and showed better skin permeation and retention than the conventional Karanjin lotion.

Hyperpolarization of 15N‐Pyridinium by Using Parahydrogen Enables Access to Reactive Oxygen Sensors and Pilot In Vivo Studies

Hyperpolarization of 15N‐Pyridinium by Using Parahydrogen Enables Access to Reactive Oxygen Sensors and Pilot In Vivo Studies

A Novel Photosensitizer Based 450-nm Blue Laser-Mediated Photodynamic Therapy Induces Apoptosis in Colorectal Cancer – in Vitro and in Vivo Study

A Novel Photosensitizer Based 450-nm Blue Laser-Mediated Photodynamic Therapy Induces Apoptosis in Colorectal Cancer – in Vitro and in Vivo Study

Studying the Efficacy of Copper Oxide Loaded Graphitic Carbon Nitride Nanosheets on VEGF-Induced Angiogenesis in Chick Chorioallantoic Membrane (CAM Assay) In Vivo Studies and Cytotoxicity in Human Hep3B Liver Cancer Cell Lines

Studying the Efficacy of Copper Oxide Loaded Graphitic Carbon Nitride Nanosheets on VEGF-Induced Angiogenesis in Chick Chorioallantoic Membrane (CAM Assay) In Vivo Studies and Cytotoxicity in Human Hep3B Liver Cancer Cell Lines

Cannabis and cancer: unveiling the potential of a green ally in breast, colorectal, and prostate cancer.

Cancer comes in second place on the list of causes of death worldwide. In 2018, the 5-year prevalence of breast cancer (BC), prostate cancer (PC), and colorectal cancer (CRC) were 30%, 12.3%, and 10.9%, respectively. Cannabinoids are chemicals derived from the Cannabis sativa plant; the most investigated cannabinoids are cannabinol, delta 9-tetrahydrocannabinol (Δ9-THC), and cannabidiol. In humans, the endogenous endocannabinoid system consists of endocannabinoids, cannabinoids receptors (CBs), and enzymes that degrade the endocannabinoids. In this review, we will review the most recent literature for evidence that discusses the role of cannabis in the treatment of the three types of neoplasms mentioned. Studies have proved that BC cells express CB receptors; many in-vivo studies showed that cannabinoids cause apoptosis and inhibit proliferation and migration. Also, researchers found that treating BC mice with THC and JWH-133 (CB2 receptor agonist) slowed the tumor growth. Regarding CRC, cannabidiol was found to decrease the viability of chemotherapy-resistant CRC cells and inhibit metastasis by antagonizing the G-protein-coupled receptor 55 (GPR55; a novel cannabinoid receptor) necessary for metastasis. Moreover, cannabidiol had anti-angiogenetic effects by reducing the expression of vascular endothelial growth factor (VEGF) in addition to anti-inflammatory effects. Finally, studies demonstrated that PC cells highly express CB1 and CB2 receptors and that cannabinoids are capable of inhibiting the release of exosomes and microvesicles related to cancer progression. Cannabinoids also have antiproliferative, anti-invasive, anti-fibroblastic, cell cycle arrest, and proapoptotic effects on PC cells.

Biopharmaceutical distribution and pharmacodynamic evaluation of intra nasal in-situ gel of Lamotrigine for brain targeted drug delivery

Background: The present research investigates the nasal delivery of Lamotrigine by incorporating it into a natural in-situ gelling system. Additionally, the retention of the drug in the nasal cavity was enhanced by employing the natural mucoadhesive polymer locust bean gum (LBG). A preliminary investigation was conducted to determine the optimal concentration of gellan gum. The dosage of the drug was calculated using the Robinson Erikson equation. The central composite design was utilized to optimize the influence of individual variables such as gellan gum and locust bean gum on various responses, including gelation time, gel viscosity, mucoadhesive strength, and the time taken for the drug to release half of its initial concentration (t50). The goal of the current study was to evaluate the in-vivo effectiveness of intra nasal in-situ gel of Lamotrigine. Methodology: The pharmacokinetic and tissue distribution studies were carried out to evaluate the brain targeting efficiency of lamotrigine. Blood samples and tissues of various vital organs like brain, liver, kidneys and heart were obtained at different time intervals, plasma and tissue concentration of Lamotrigine was estimated by reverse phase HPLC. Results: According to the pharmacokinetic analysis, Cmax and AUC0-α is found to be significantly more (P&lt;0.05) for nasal route compared to oral route. In comparison to the oral route, Cmax and AUC0-α was 7 and 6.5 folds more for IN route. The absolute bioavailability was found to be 159.07%. with regard to the oral group, minimal drug was present in any of the other tissue samples. In the pharmacodynamic data also the formulation through nasal route showed a significant difference compared to oral route (pure drug suspension) delivery in PTZ induced study. Keywords: Lamotrigine, in-vivo study, tissue distribution, pharmacodynamics

Expression of a unique M. tuberculosis DNA MTase Rv1509 in M. smegmatis alters the gene expression pattern and enhances virulence.

Mycobacterium tuberculosis (M. tb) genome encompasses 4,173 genes, about a quarter of which remain uncharacterized and hypothetical. Considering the current limitations associated with the diagnosis and treatment of tuberculosis, it is imperative to comprehend the pathomechanism of the disease and host-pathogen interactions to identify new drug targets for intervention strategies. Using in-silico comparative genome analysis, we identified one of the M. tb genes, Rv1509, as a signature protein exclusively present in M. tb. To explore the role of Rv1509, a likely methyl transferase, we constructed a knock-in Mycobacterium smegmatis (M. smegmatis) constitutively expressing Rv1509 (Ms_Rv1509). The Ms_Rv1509 led to differential expression of many transcriptional regulator genes as assessed by RNA-seq analysis. Further, in-vitro and in-vivo studies demonstrated an enhanced survival of Ms_Rv1509 inside the host macrophages. Ms_Rv1509 also promoted phagolysosomal escape inside macrophages to boost bacterial replication and dissemination. In-vivo infection studies revealed that Ms_Rv1509 survives better than BCG and causes pathological manifestations in the pancreas after intraperitoneal infection. Long-time survival of Ms_Rv1509 resulted in lymphocyte migration, increased T regulatory cells, giant cell formation, and likely granuloma formation in the pancreas, pointing toward the role of Rv1509 in M. tb pathogenesis.

An antibiotic efficacy comparative study between market-prescribed and solid-lipid fluoroquinolone ophthalmic nanoformulation against conjunctivitis

Besifloxacin hydrochloride (BSF) drug substance (DS), is effective against gram-positive and gram-negative microorganisms. BSF (liquid suspension form) is already available in two different market brands: Besivance and Besix. Both of these commercialized drug products (DP) have lower mucoadhesive characteristics, therefore they spend less time in contact with various ocular tissues (cornea and conjunctiva). This research work emphasized the design, development, and optimization of BSF-loaded solid-lipid nanoparticles (BSF@SLN) to increase antibacterial activity by enhancing drug absorption through passive diffusion techniques in the ocular organ compared to conventional dosage forms. The SLN was prepared through a very simple process hot homogenization process using glyceryl monostearate and polysorbate-80 along with poloxamer-188 and water for injection. Various characterization techniques like FTIR, DSC, and XRD were performed to check the compatibility between DS and excipients. The preliminary formulation of SLN was characterized through zeta potential, polydispersity index, and particle size techniques. The developed SLN was optimized following 32 factorial designs. Surface morphology and size of optimized BSF@SLN ophthalmic DP were confirmed by using advanced microscopic techniques such as SEM. In-vitro release of optimized BSF@SLN ophthalmic DP was performed by using two chambers of Franz diffusion cell. Stability studies of optimized BSF@SLN ophthalmic nanoformulations were tested for up to 6 months at 25°C ± 2°C/60% ± 5% RH. The antimicrobial activity of optimized ophthalmic nanoformulation was found 2.76 times more effective compared to the Besix eye drop. In-vivo study of BSF@SLN ophthalmic nanoformulations was carried out with an eye irritancy test and compared with marketed DP (Besix). and found significant pharmacological.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

CRISPR-Cas Genome Editing in Ex Vivo Human Lungs to Rewire the Translational Path of Genome-Targeting Therapeutics.

The ongoing advancements in CRISPR-Cas technologies can significantly accelerate the preclinical development of both invivo and ex vivo organ genome-editing therapeutics. One of the promising applications is to genetically modify donor organs prior to implantation. The implantation of optimized donor organs with long-lasting immunomodulatory capacity holds promise for reducing the need for lifelong potent whole-body immunosuppression in recipients. However, assessing genome-targeting interventions in a clinically relevant manner prior to clinical trials remains a major challenge owing to the limited modalities available. This study introduces a novel platform for testing genome editing in human lungs ex vivo, effectively simulating preimplantation genetic engineering of donor organs. We identified gene regulatory elements whose disruption via Cas nucleases led to the upregulation of the immunomodulatory gene interleukin 10 (IL-10). We combined this approach with adenoviral vector-mediated IL-10 delivery to create favorable kinetics for early (immediate postimplantation) graft immunomodulation. Using ex vivo organ machine perfusion and precision-cut tissue slice technology, we demonstrated the feasibility of evaluating CRISPR genome editing in human lungs. To overcome the assessment limitations in ex vivo perfused human organs, we conducted an invivo rodent study and demonstrated both early gene induction and sustained editing of the lung. Collectively, our findings lay the groundwork for a first-in-human-organ study to overcome the current translational barriers of genome-targeting therapeutics.

A comparative study between nanostructured lipid carriers and invasomes for the topical delivery of luteolin: Design, optimization and pre-clinical investigations for psoriasis treatment

Psoriasis is an inflammatory skin condition manifested by hyper-proliferation and reactive aberrant epidermal differentiation, in which genetic and environmental factors have a significant role. The current context is focused on designing novel nanovesicular systems (invasomes) incorporating terpenes with reported anti-inflammatory potential and loaded with a nutraceutical compound (luteolin/Lut) for treatment of psoriasis. Additionally, their topical efficacy in psoriasis treatment compared to lipid-based nanocarriers (nanostructured lipid carriers) was investigated. Invasomes were assessed regarding their particle size (PS), zeta potential (ζ-potential), drug entrapment (EE%), storage stability, in-vitro drug release profile and release kinetics. The optimized vesicles were investigated for their ex-vivo skin deposition and in-vitro anti-inflammatory potential in comparison with nanostructured lipid carriers (NLCs). The optimized formulation was selected to carry out the in-vivo study using rat model of imiquimod-induced psoriasis. Luteolin-invasomes were found to have spherical shape and promising colloidal properties. They possessed PS ranging from 277.80 to 812.91 nm, negative ζ-potential (−35.22–38.55 mV), and high EE% values, which ranged from 89.38 to 99.75 %. Furthermore, they exhibited good stability properties and significant sustainment of drug release in comparison to NLCs. In addition, they were able to enhance Lut deposition by 2.1-fold in the stratum corneum (SC) and 5.5-fold in epidermis and dermis compared to control suspension of Lut. Moreover, invasomes showed more potential to retain Lut into deep skin layers 1.5-fold higher than NLCs. They also displayed higher in-vitro anti-inflammatory activity compared to plain invasomes and control suspension, and comparable activity compared to NLCs. In the in-vivo animal study, the ability of Lut to alleviate psoriatic symptoms was significantly enhanced after its encapsulation in invasomal dispersions, where Lut-invasomes possessed a great inhibitory potential compared to the control Lut suspension, and even to Lut-NLCs. This suggests their efficiency in treating psoriasis, delineating them promising for further use in treating other inflammatory skin conditions.

The Potential Anti-psoriatic Effects of Andrographolide: A Comparative Study to Topical Corticosteroids.

Andrographolide (AP), a bioactive anti-inflammatory compound of Sambiloto, inhibits NF-κB, TNF-α, and interleukin IL-6. Nowadays, molecular docking simulation between AP and dexamethasone against NF-κB receptor presented the energy AP higher than dexamethasone. This becomes a potential treatment for psoriasis. This manuscript reported the effectiveness of AP from Sambiloto in treating psoriasis compared to topical steroids. This study conducted TLC analysis of AP content and its metabolite impurities, emulgel formulation, molecular docking, in-silico skin toxicity study, and in-vivo anti-psoriatic activity. This was a combination study of an in-silico study and an in-vivo study. This in-silico study was analyzed through multivariate statistical analysis (PCA) to elucidate the data constellation relationship of andrographolide derivatives with several target proteins. The intervention was performed in seven days. The PASI score, molecular parameters (IL-6, IL-17, VEGF, and TNF-a levels), and histopathological findings were assessed. Molecular docking results revealed andrographolide to exhibit a relatively high binding affinity towards IL-6, NF-kB, and TNF-α which is comparable to the corticosteroids, andrographolide also shares similar residue interaction profile with each of the respective protein's native ligand. In the in-vivo study, we found several parameters statistically significantly different regarding the intervention, including final PASI score (p = 0.017), redness (p = 0.017), scale (p = 0.040), thickness (p = 0.023), total histopathology of psoriasis score (p = 0.037), keratin layer score (p = 0.018). Emulgel AP 0.1% could lower the anti-inflammatory agent, which is vital to psoriasis progression.

P-gp inhibition and enhanced oral bioavailability of amikacin Sulfate: A novel approach using Thiolated Chito-PEGylated Lipidic Hybrids

This study aimed to develop oral lipidic hybrids of amikacin sulfate (AMK), incorporating thiolated chitosan as a P-glycoprotein (P-gp) inhibitor to enhance intestinal absorptivity and bioavailability. Three formulations were designed: PEGylated Liposomes, Chitosan-functionalized PEGylated (Chito-PEGylated) Lipidic Hybrids, and Thiolated Chito-PEGylated Lipidic Hybrids. The physical characteristics of nanovesicles were assessed. Ex-vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted to evaluate the formulations’ potential to enhance AMK intestinal permeability. In-vivo pharmacokinetic studies in rats and histological/biochemical investigations assessed the safety profile and oral bioavailability. The AMK-loaded Thiolated Chito-PEGylated Lipidic Hybrids exhibited favorable physical characteristics, higher ex-vivo permeation parameters, and verified P-gp inhibition via CLSM. They demonstrated heightened oral bioavailability (68.62% absolute bioavailability) and a sufficient safety profile. Relative bioavailability was significantly higher (1556.3% and 448.79%) compared to PEGylated Liposomes and Chito-PEGylated Lipidic Hybrids, respectively, indicating remarkable oral AMK delivery with fewer doses, reduced side effects, and enhanced patient compliance.

Appraising the antibacterial/antioxidant activities of vancomycin as a novel nano-platfom: Characterization, in-vitro assessment and in-vivo radio-tracking in animal models

The antibacterial nano-platforms have recently been developed as a result of an increasing prevalence of the bacterial resistance to various standard antibiotics. The aim of this study is to improve the vancomycin antibacterial efficacy against various resistant-bacteria using a unique nano-platform. Vancomycin functionalized silver nanoparticles (Ag-VanNPs) were properly synthesized showing a significant UV–Vis absorbance at 426 nm, average particle size of 20 ± 4.3 nm, mean hydrodynamic size of 185 ± 8.5 nm and zeta potential of +19 mV. Ag-VanNPs were investigated for its in-vitro antibacterial activity against various (G + ve and G-ve) bacterial strains declaring a synergistic antibacterial action that outperformed pure vancomycin. Compared to free vancomycin, Ag-VanNPs had showed significant reduction in MIC/MBC concentrations with FIC/FBC indices ≤0.5, suggesting a synergistic action with fewer adverse effects. The in-vitro viability and hemolysis studies revealed that Ag-VanNPs were non-toxic and biocompatible. The in-vivo studies of [131I] I–Ag-VanNPs in normal mice model showed their in-vivo stability and elimination mainly via hepatobiliary and renal pathways. Moreover, significant accumulations of [131I] I–Ag-VanNPs in the inflammatory muscle were seen in the in-vivo distribution of the inflamed mice model, which was represented by the potential T/NT ratios ≥1 at all research time points. Therefore, [131I] I–Ag-VanNPs may have better antibacterial activities against both kinds of Gram bacteria in addition to being a promising anti-inflammatory nano-radiopharmaceutical.