In-vivo Studies Research Articles

Comparative Evaluation of Endo Ice® Refrigerant Spray, Endo Frost® Refrigerant Spray and Topical Anesthetic Agent Precaine B® on the Pain Perception in Children Prior to Administration of Local Anaesthesia – An Invivo Study

To compare and evaluate the efficacy of Endo Ice® refrigerant spray, Endo Frost® refrigerant spray and topical anaesthetic agent Precaine B® on the pain perception during local anaesthesia administration in pediatric dental patients.  Material and methods: A total of 87 participants in the age group of 6-12 years were divided into 3 groups randomly with 29 in each group. The cotton applicator sprayed with Endo Ice was held in contact with the buccal mucosa for 10 seconds. Immediately after the removal of the cotton applicator, inferior alveolar nerve block was administered. Similarly, Endo Frost was used on the participants. 0.1 mg of Precaine B was applied over the injection site contacting the buccal mucosa using sterile cotton applicator. FLACC evaluation was done by one trained personnel during the local anaesthesia administration. Following the local anesthesia, the participants were asked to rate their pain experience using VAS.  Results: The mean score of the Endo ice, Endo frost, and Precaine B were 4.3793, 4.4828 and 5.5517 respectively using the FLACC scale. The mean score of the Endo ice, Endo frost, and Precaine B were 4.2069, 4.2069 and 4.931 respectively using the VAS scale. Greater reduction in pain perception were observed in Endo Ice group followed by Endo Frost group and Precaine group. It was not statistically significant (p<0.005).  Conclusion: Endo ice, Endo frost and Precaine B were effective in reducing the pain perception in children, thereby reducing their fear and anxiety. Endo Ice group showed greater reduction in pain perception and higher efficacy than other groups, even though the results were not statististically significant.

Enhanced Anti-Obesity Effects of Euphorbia Kansui Extract through Macrophage and Gut Microbiota Modulation: A Real-World Clinical and In Vivo Study.

Rising obesity and associated multi-systemic complications amplify the health burden. Euphorbia kansui (EK) extract is clinically recognized for managing obesity. In a human study, 240 obese individuals were categorized into two cohorts: those receiving solely herbal medicine (HM group) and those administered EK concomitantly with herbal medicine (EK group). An in vivo examination using C57BL/6-Lepob/Lepob mice elucidated mechanisms involving macrophages and gut microbiota with associated metabolic advantages. The clinical study revealed a significant 7.22% body weight reduction during 91.55 average treatment days and examined 16.71% weight loss at 300 days after treatment. In whole subjects, 60.4%, 21.3%, and 6.3% achieved weight reductions exceeding 5%, 10%, and 15%, respectively. Impressively, the EK group exhibited superior weight loss compared to the HM group (EK: -7.73% vs. HM: -6.27%, p = 0.012). The anti-obesity effect was positively associated with EK therapy frequency and herbal medicine duration. In the in vivo study, EK significantly improved insulin sensitivity and mitigated infiltration of adipose tissue macrophages (ATMs) by modulating the CD11c+ and CD206+ subtypes. EK also correlated with increased Bacteroidetes and Firmicutes populations and reduced Proteobacteria and Verrucomicrobia. Consequently, EK is an effective adjunctive anti-obesity therapy offering metabolic benefits by modulating ATMs and gut microbiota profiles.

Chromatographic fingerprinting of ipratropium and fenoterol in their novel co-formulated inhaler treating major respiratory disorders; application to delivered dose uniformity testing along with greenness and whiteness assessment

Ipratropium bromide (IPR) and fenoterol hydrobromide (FEN) have recently been combined in a promising inhaler to treat two prevalent inflammatory illnesses of the airways: bronchial asthma and chronic obstructive pulmonary disease (COPD). The necessity for a single, sensitive, and trustworthy analytical approach to cover the diverse and necessary tests of in-vitro and in-vivo studies is greatly grown with the rising production of new fixed combinations. Two novel, selective and environmentally friendly LC techniques were developed in order to guarantee precise measurement of IPR and FEN in their challenging formulation. The initial technique involved high-performance thin-layer chromatography (HPTLC) in conjunction with densitometric quantification. Chromatographic separation was attained on HPTLC plates utilizing ethyl acetate - ethanol - acetic acid (5.0:5.0:0.1, by volume) as a developing system. Densitometric quantification of the separated bands was carried out at 220.0 nm over concentration ranges of 0.50–15.0 µg/band for IPR and 0.50–12.0 µg/band for FEN. High-performance liquid chromatography (HPLC) paired with diode array detection (DAD) was the core of the second technique. The optimized separation was achieved on a Zorbax SB C18 (150 × 4.6 mm, 5 μm) column with a combination of 10.0 mM potassium dihydrogen orthophosphate, pH 5.0 ± 0.1, adjusted with o-phosphoric acid and methanol (70:30, v/v) as the mobile phase and pumped at flow rate of 1.0 mL/min. The peaks were monitored at 220.0 nm using diode array detection, achieving linearity range of 5.0–200.0 µg/mL for both drugs. The ICH criteria have been verified and both methods have been confirmed to be valid, and successfully applied for assay the cited drugs in the Atrovent® comp HFA metered dose inhaler as well as delivered dose uniformity testing of the final product. Finally, whiteness appraisal and several state-of-the-art green evaluation metrics were applied to evaluate the sustainability of the proposed methods. The suggested approaches produced promising results and are the first simple and sustainable methodologies for the simultaneous quantification of both drugs in different real samples, all of which strongly suggest their application in quality control laboratories.

Local delivery of pamidronate with collagen matrix mitigates buccal bone resorption following immediate implant placement - An experimental invivo study.

The aim of this experimental invivo pilot study was to evaluate the effect of the local delivery of pamidronate within a collagen membrane on the changes in the buccal soft and hard tissue dimensions at the time of immediate implant placement and whether this effect was influenced by the placement of bone substitutes. In six beagle dogs, the distal roots of the third and fourth premolars were extracted, and immediate implants were placed. Treatment groups were randomly allocated to each socket: (i) covering the buccal bone with pamidronate-soaked collagen membrane (BP group), (ii) filling the gap defect with synthetic bone substitute (BS group), (iii) filling the gap defect with synthetic bone substitute and covering the buccal bone with pamidronate soaked collagen membrane (BP/BS group), (iv) no treatment (control group). Intraoral scanning was performed immediately after the surgery and at 20 weeks. Histomorphometric and micro-computed tomography (CT) outcomes were evaluated at 20 weeks. The micro CT analysis demonstrated that the BP group showed no apparent difference in vertical bone level with residual mesial root area, while control group showed significant buccal bone resorption at the implant site. The histomorphometric analysis demonstrated that the vertical bone level of buccal plate was significantly differed between the BP and control group (0.34 ± 0.93 and 1.27 ± 0.56 mm, respectively; p = .041). There was no statistically significant difference in the horizontal ridge width (HRW 1, 2, 3) among the groups. Also, the thickness, height and buccal contours of the soft tissue did not reveal significant changes among the groups. The local delivery of pamidronate to the outer surface of the buccal wall at the time of immediate implant placement effectively limits buccal bone resorption. The results from the present investigation should be interpreted with caution, as well as its clinical translatability. Further investigation is needed to understand the pamidronate binding and releasing kinetic, as well as the ideal carrier of this drug for its topical application.

Development, Stability, and In Vitro/In Vivo Studies of Volatile Oil Pickering Emulsion Stabilized by Modified Amber.

Volatile oil stabilization strategies based on encapsulation with a large number of excipients limit further applications. The primary objective of this study is to improve the stability of volatile oils using Pickering emulsion (PE) stabilized by Chinese medicinal powder based on the principle of "integrating drug and excipient". Modified amber was acquired through surface modification, and a stable oil-in-water PE loaded with Acorus tatarinowii volatile oil (ATVO) was constructed from modified amber. The stability, including the peroxide value (PV), malondialdehyde (MDA) content, and the content and composition of volatile components in modified amber-PE (MAPE) under intense light exposure, was analyzed deeply. In addition, the in vitro release and pharmacokinetics of MAPE and ATVO were investigated. The results demonstrate that the PV and MDA content in MAPE were significantly lower than in free ATVO, and the content and composition of volatile components in MAPE were closer to those in untreated ATVO. The release kinetics of β-asarone and α-asarone in MAPE demonstrated rapid and higher release, and pharmacokinetic studies show that MAPE has better bioavailability. This research provides a distinctive Chinese medicine solution to address the vaporization of volatile oil in solid formulations.

Detection of microplastics in human tissues and organs: A scoping review.

Research on microplastics has largely focused on the environment and marine organisms until recently. A growing body of evidence has detected microplastics in human organs and tissues, with their exact entry routes being unclear and their potential health effects remain unknown. This scoping review aimed to characterise microplastics in human tissues and organs, examine their entry routes and addressing gaps in research analytical techniques. Eligibility criteria included English language full text articles, in-vivo human studies only, and searching the databases using pre-defined terms. We based our analysis and reporting on the PRISMA guideline and examined the quality of evidence using the risk of bias assessment tool. Of 3616 articles screened, 223 evaluated and 26 were eventually included in this review. Nine were high risk for bias, three were unclear risk and the rest low risk for bias. Microplastics were detected in 8/12 human organ systems including cardiovascular, digestive, endocrine, integumentary, lymphatic, respiratory, reproductive and urinary. Microplastics were also observed in other human biological samples such as breastmilk, meconium, semen, stool, sputum and urine. Microplastics can be characterised based on shape, colours, and polymer type. Potential entry routes into human included atmospheric inhalation and ingestion through food and water. The extraction techniques for analysis of microplastics in human tissues vary significantly, each offering distinct advantages and limitations. Microplastics are commonly detected in human tissues and organs, with distinct characteristics and entry routes, and variable analytical techniques exist.

Formulation and optimization of olanzapine-carboxylic acid cocrystals orodispersible tablets: In-vitro/ In-vivo study

Oromucosal delivery of olanzapine (OLZ) is an optimal strategy to overcome low oral bioavailability as well as improve medication adherence. However, its poor aqueous solubility may hinder its absorption through the buccal mucosa. The aim of the study is to enhance OLZ solubility and dissolution via cocrystal formation, followed by incorporation into an orodispersible tablet (ODT) based on an effervescent mixture and crospovidone as a superdisintegrant mixture. OLZ was cocrystallized with different carboxylic acids using slow solvent evaporation, and the optimal cocrystal formula was subjected to solid state characterization. Central composite design (CCD) was used in the modeling and optimization of the ODT independent variables (amounts of crospovidone and effervescent mixture). The optimized OLZ cocrystal ODTs were subjected to microenvironmental pH, stability, and in-vivo studies. The results revealed that the OLZ:itaconic acid at 1:1 M ratio showed a 7.86 fold increase in OLZ solubility and 86.71 ± 1.07 % dissolution efficiency (DE60 %) with FTIR, XRPD, and DSC diffractograms that confirmed the cocrystal formation. The optimized OLZ cocrystal ODTs exhibited hardness of 3.6 ± 0.1 kg/cm2, disintegration time of 11.66 ± 1.52 s, wetting time of 36.33 ± 2.51 s, and 94.26 ± 2.77 % OLZ released within 15 min with a DE60 % of 91.65 ± 0.98 %. Finally, the optimized OLZ cocrystal ODTs showed a significant (p < 0.01) higher Cmax and AUC with a relative bioavailability of 139.08 % compared to the Schisolazine©10 mg ODTs. These results suggest that OLZ:itaconic acid cocrystal incorporated into an ODT containing a superdisintegrant mixture of effervescence mixture and crospovidone is a potential approach for enhancement of oromucosal delivery of OLZ.

“In Vivo Study on the Possible Desensitizing Role of Hydrocortisone versus Fluoride on the Dental Pulp of Albino Rat Incisor Subjected to Bleaching”

“In Vivo Study on the Possible Desensitizing Role of Hydrocortisone versus Fluoride on the Dental Pulp of Albino Rat Incisor Subjected to Bleaching”

Antipsoriatic Effect of Silymarin NLCs Based Gel: In Vitro and In Vivo Activity.

Psoriasis is a chronic inflammatory disorder affecting over 100 million people, requires long-term therapy. Current treatments offer only symptomatic relief. However, phytoconstituents-based therapies like Silymarin (SLM) have shown promising effects. The study aims to develop, optimize, and evaluate a novel stable SLM NLC gel to improve anti-psoriatic activity by enhancing its permeability and retention into the dermal layer. SLM NLC formulation was prepared and optimized using 32 full factorial designs. The formulation was evaluated for the particle size, PDI, zeta potential, and % entrapment efficiency, evaluated by Transmission electron microscopy and thermal analysis. The freeze dried and prepared NLC-loaded gel was evaluated for physicochemical parameters, ex-vivo, and in-vivo studies. SLM-loaded NLC shows 624nm particle size, 0.41 PDI, 92.95% entrapment efficiency, and -31.6mV zeta potential. The sphere form of NLCs was confirmed using TEM. Controlled drug release was observed in ex vivo studies, low PASI score compared to disease control. Further, the levels of IL-6, TNF-α, and NF-κB were also reduced. The results are supported by histopathology showing minimal parakeratosis indicated in the SLM NLC-treated group. Prepared NLC-based shows enhance topical penetration and decrease the thickness of psoriatic plaques in the in vivo study.

Higher solubility and lower onset temperature of protein denaturation increase the osteoconductive capacity of collagen membranes: A preclinical invivo study.

Collagen membranes are extensively used for guided bone regeneration procedures, primarily for horizontal bone augmentation. More recently, it has been demonstrated that collagen membranes promote bone regeneration. Present study aimed at assessing if structural modifications of collagen membranes may enhance their osteoconductive capacity. Twenty-four adult Wistar rats were used. Bilateral calvaria defects with a diameter of 5 mm were prepared and covered with prototypes of collagen membranes (P1 or P2). The P1 membrane (positive control) presented a lower onset temperature of protein denaturation and a higher solubility than the P2 membrane (test). The contralateral defects were left uncovered (NC). After 1 and 4 weeks, the animals were euthanized. A microcomputed tomography analysis of the harvested samples was performed within and above the bony defect. Undecalcified ground sections were subjected to light microscopy and morphometric analysis. Bone formation was observed starting from the circumferential borders of the defects in all groups at 1-week of healing. The foci of ossification were observed at the periosteal and dura mater sites, with signs of collagen membrane mineralization. However, there was no statistically significant difference between the groups. At 4 weeks, remnants of the collagen fibers were embedded in the newly formed bone. In the P2 group, significantly more bone volume, more new bone, and marrow spaces compared to the NC group were observed. Furthermore, the P2 group showed more bone volume ectocranially then the P1 group. Bone formation subjacent to a P2 membrane was superior than subjacent to the P1 membrane and significantly better compared to the control. Modifications of the physico-chemical properties may enhance the osteoconductive competence of collagen membranes, supporting bone formation outside the bony defects.

Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent 177Lu-Labeled Radiohapten.

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic γ- and β-emitting isotope 177Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [177Lu]Lu-Gemini was prepared with no-carrier-added 177LuCl3 to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-177Lu-Gemini was verified invitro. Subsequently, we evaluated biodistribution and whole-body clearance for [177Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [177Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([177Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [177Lu]Lu-Gemini) in mouse models. Results: Initial invivo studies showed that [177Lu]Lu-Gemini behaved similarly to [177Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [177Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [177Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor-to-normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [177Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [177Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [177Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [177Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [177Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered 177Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).

In Silico and In Vivo Studies of β-Sitosterol Nanoparticles as a Potential Therapy for Isoprenaline-Induced Cognitive Impairment in Myocardial Infarction, Targeting Myeloperoxidase.

This study aimed to compare the effects of β-sitosterol nanoparticles (BETNs) and β-sitosterol (BET) on cognitive impairment, oxidative stress, and inflammation in a myocardial infarction (MI) rat model using in silico and in vivo methods. β-Sitosterol (BET) and myeloperoxidase (MPO) ligand-receptor binding affinities were evaluated using Autodock Vina for docking and Gromacs for dynamics simulations. BET nanoparticles, prepared via solvent evaporation, had their size confirmed by a nanoparticle analyzer. ISO-induced cognitive impairment in rats was assessed through Morris water maze and Cook's pole climbing tests. Oxidative stress, inflammation, and cardiac injury were evaluated by measuring GSH, SOD, MDA, MPO, CkMB, LDH, lipid profiles, and ECGs. Histopathology of the CA1 hippocampus and myocardial tissue was performed using H&E staining. In silico analyses revealed strong binding affinities between BET and MPO, suggesting BET's potential anti-inflammatory effect. BETN (119.6 ± 42.6 nm; PDI: 0.809) significantly improved MI-induced cognitive dysfunction in rats (p < 0.001 ***), increased hippocampal GSH (p < 0.01 **) and SOD (p < 0.01 **) levels, and decreased hippocampal MDA (p < 0.05 *) and MPO levels (p < 0.01 **). BETNs also elevated cardiac GSH (p < 0.01 **) and SOD (p < 0.01 **) levels and reduced cardiac MPO (p < 0.01 **), CkMB (p < 0.001 **) and LDH (p < 0.001 **) levels. It restored lipid profiles, normalized ECG patterns, and improved histology in the hippocampal CA1 region and myocardium. Compared with BET treatment, BETNs were more effective in improving cognitive impairment, oxidative damage, and inflammation in MI rats, suggesting its potential in treating cognitive dysfunction and associated pathological changes in MI.

Inhalation of SP-101 Followed by Inhaled Doxorubicin Results in Robust and Durable hCFTRΔR Transgene Expression in the Airways of Wild-Type and Cystic Fibrosis Ferrets.

Cystic fibrosis (CF) is a serious genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Approved small molecule therapies benefit the majority of people with CF (pwCF), but unfortunately not all. Gene addition offers a mutation agnostic treatment option for all pwCF. SP-101 is an adeno-associated virus gene therapy vector (AAV2.5T) that has been optimized for efficient human airway cell transduction, and that contains a functional and regulated shortened human CFTR minigene (hCFTRΔR) with a small synthetic promoter/enhancer. To understand SP-101 airway distribution, activity, and the associated immune response, invivo studies were performed in wild-type and CF ferrets. After single dose inhaled delivery of SP-101, followed by single dose inhaled doxorubicin (an AAV transduction augmenter) or saline, SP-101 vector genomes were detected throughout the respiratory tract. hCFTRΔR mRNA expression was highest in ferrets also receiving doxorubicin and persisted for the duration of the study (13 weeks). Pre-existing mucus in the CF ferrets did not present a barrier to effective transduction. Binding and neutralizing antibodies to the AAV2.5T capsid were observed regardless of doxorubicin exposure. Only a portion of ferrets exhibited a weak T-cell response to AAV2.5T and no T-cell response was seen against hCFTRΔR. These data strongly support the continued development of inhaled SP-101, followed by inhaled doxorubicin, for the treatment of CF.

Efficacy of NKG2D CAR-T cells with IL-15/IL-15Rα signaling for treating Epstein-Barr virus-associated lymphoproliferative disorder

Epstein-Barr virus (EBV) related post-transplant lymphoproliferative disorder (EBV-PTLD) is a life-threatening complication after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), for which no standard therapeutic means have been developed. Significant increase expression of natural killer group 2 member D ligands (NKG2DLs) was observed on B-lymphoblastoid cells of EBV-PTLD, indicating NKG2DLs as potential therapeutic targets for treatment of EBV-PTLD. In this study, the recombinant constructs of NKG2D CAR and IL-15/IL-15Rα-NKG2D CAR were generated with a retroviral vector and then transduced to human T cells to produce NKG2D CAR-T and IL-15/IL-15Rα-NKG2D CAR-T cells, respectively. B-lymphoblastoid cell lines (B-LCLs) and the xenografted mouse models were established to evaluate the efficacy of these CAR-T cells. IL-15/IL-15Rα-NKG2D CAR-T cells exhibited superior proliferation and antigen-specific cytotoxic effect compared to NKG2D CAR-T, as IL-15/IL-15Rα signaling promoted the expansion of less differentiated central memory T cells (TCM) and increased expression of CD107a and IFN-γ. Moreover, EBV DNA load was dramatically reduced, and 80% B-LCL cells were eliminated by IL-15/IL-15Rα-NKG2D CAR-T cells after co-culturing. In-vivo study confirmed that IL-15/IL-15Rα-NKG2D CAR-T cell therapy significantly enhanced antiviral efficacy in mice, as the serum load of EBV after IL-15/IL-15Rα-NKG2D CAR-T cell infusion was 1500 times lower than the untreated control (P < 0.001). The enhanced efficacy of IL-15/IL-15Rα-NKG2D CAR T cells was probably due to the IL-15/IL-15Rα signaling improved homing and persistence of NKG2D CAR-T cells in vivo, and increased the production of IFN-γ, Perforin, and Granulysin. In conclusion, NKG2D CAR-T cells co-expressing IL-15/IL-15Rα promoted the central memory CAR T cell proliferation and improved the homing and persistence of CAR T cells in vivo, resulting in enhanced anti-tumor and anti-viral effects in treating EBV-PTLD.

Quality by design steered approach for co-encapsulation of timolol maleate and dorzolamide hydrochloride in injectable liposomes

Glaucoma is caused by high intraocular pressure, which can causes blindness. Combinations of timolol and dorzolamide are used for its treatment with a requirement of multiple dosing with dosing being twice or four times a day. Conventional eye drops have poor pre-corneal retention and is thus less available for action. This study utilizes principles of Quality by Design for formulation of injectable liposomes coloaded with timolol maleate and dorzolamide HCl, which overcomes limitations of conventional eye drops. For implementation of Quality by Design principles a systematic approach involving defining Quality Target Product Profile, identification of Critical Quality Attributes, mapping Critical Quality Attributes to Critical Process Parameters and Critical Material Attributes, Failure Mode and Effect Analysis based risk assessment, Taguchi screening, and 32 full factorial Design of Experiments design were utilized. A robust model for formulation of coloaded liposomes was successfully developed. Design of Experiments approach allowed to obtain optimized batch having particle size of 116.1 nm, encapsulation efficiency of dorzolamide HCl of 72.12 % and encapsulation efficiency of timolol maleate of 71.94 %. In-vitro drug release showed a sustained release for 4 days. The prepared formulation was in the desired osmolarity range. Biosafety was proved using histopathological characterization. In-vivo studies for assessing the Intra Ocular Pressure reduction showed that there was no significant difference in Intra Ocular Pressure reduction between prepared liposomes and marketed formulation but were superior than marketed formulation because of less fluctuations in Intra Ocular Pressure. Prepared coloaded injectable liposomes lays the foundation for further research in the area and can be translated from to bench side for commercial clinical use.

Clinical efficiency of new generation elastomeric ligatures over conventional: An in-vivo study

Friction being an imperative element in clinical orthodontics affects all stages of treatment and high frictional forces can affect the treatment duration and outcome in a deleterious manner. This study was done to appraise frictional resistance of non-conventional elastomeric modules in comparison with conventional elastomeric modules, during the retraction of teeth. The study sample size includes 30 patients (11 males and 19 females) undergoing orthodontic treatment. They were grouped into 3, namely, Group A- Slide nonconventional elastomeric ligatures Group B- super slick nonconventional elastomeric ligatures, and Group C- the conventional ligature. The study models were obtained to assess canine retraction rate, anchor loss, canine rotation, and molar rotations at different time intervals and subjected to statistical analysis. : The canine retraction rate(maxilla) for Group A, B and C was 1.674+/-0.092, 1.187+/-0.156, and 1.147+/-0.113,(mandible)1.765+0.099, 1.300+0.099 and 1.270+0.111 respectively. Mean anchorage loss(maxilla) group A- 1.054mm, group B- 1.080mm, group C -1.715mm (mandible) 1.024mm, 0.952mm and 1.664mm respectively. Canine rotation(maxilla) of Group A, B and C is 8.550+/-1.506, 5.300+/-1.386, 6.100+/-1.315and(mandible) 8.930/-+1.474, 5.830+/-1.096, 6.880+/-1.813 respectively. Mean molar rotation (maxilla) 2.580+0.735, 2.210+0.549 and 2.210+0.700 (mandible)2.900+0.541, 2.650+0.639 and 2.780+0.604 in group A, B and C respectively. Mean anchor loss was lesser in non-conventional modules, canine retraction rate was higher with Slide ligature, canine rotations were least in superslick more in Slide ligature, and rotation of molar was apparent for all the groups.

The Different Influence of Cutibacterium Acnes and Staphylococcus Epidermidis in the Lumbar Disc: An in Vivo Study in Rabbits.

Animal laboratory study. This study investigated the effects of C. acnes and S. epidermidis on the lumbar discs of rabbits, as well as the outcomes of combined infection. Many studies have indicated that bacterial infections are associated with lumbar disc degeneration (LDD). The most commonly cultured bacteria from disc tissues are Cutibacterium acne (C. acnes) and Staphylococcus epidermidis (S. epidermidis). New Zealand white rabbits (n=40) were randomly divided into control, C. acnes, S. epidermidis, and C. acnes plus S. epidermidis (i.e., combined) groups. All groups except the control were injected with 25μL of saline at L4-L5 and 25μL of bacteria (1×107 CFU/mL) at L5-L6. All injections were performed under X-ray guidance. Weight measurements, haematological evaluations, and magnetic resonance imaging were performed after 4, 8, and 12 weeks. Histological examination and gene expression detection were performed 12 weeks after surgery. Inflammatory factors in the blood and weight did not differ among the groups after 4, 8, and 12 weeks (P >0.05). However, after 4 weeks, LDD occurred in the C. acnes group, and discitis occurred in the S. epidermidis and combined groups, all of which worsened after 8 weeks. After 12 weeks, the nucleus pulposus (NP) protruded and compressed the spinal cord in the C. acnes group, and tissue staining showed decreased NP tissue and cartilaginous endplate fracture. In the S. epidermidis and combined groups, the discitis was more confined, but tissue staining revealed a significant decrease in NP tissue, and loss of the normal disc structure. In the early stage of infection in rabbits, C. acnes caused LDD, and S. epidermidis caused discitis. Co-infection with C. acnes and S. epidermidis caused discitis but was more limited in scope than infection with S. epidermidis alone.

The role of sulbactam-durlobactam in treating carbapenem-resistant Acinetobacter infections.

Infections caused by multidrug-resistant Acinetobacter baumannii present a significant global health challenge. Available treatment options are limited and frequently constrained by unfavourable safety and pharmacokinetic profiles. Sulbactam-durlobactam is a novel β-lactamase inhibitors combination specifically developed to target A. baumannii, including carbapenem-resistant strains. The purpose of this review is to assess the current evidence supporting the role of sulbactam-durlobactam in the management of A. baumannii infections. We summarize the available evidence regarding the pharmacokinetic and pharmacodynamic profiles of sulbactam-durlobactam from key in-vitro and in-vivo studies. Additionally, efficacy results from the Phase III randomized controlled trial and real-world data on sulbactam-durlobactam's use against severe A. baumannii infections are also discussed. Sulbactam-durlobactam is a promising addition to the treatment options for carbapenem-resistant A. baumannii infections. Ongoing research and vigilance are essential to monitor the development of in-vivo resistance, assess effectiveness across diverse patient populations, and explore potential synergistic combinations with other antimicrobials. Careful stewardship and comprehensive clinician education will be crucial to optimizing the clinical use of sulbactam-durlobactam.

Paraspecific neutralization capacity of polyvalent snake antivenom against Montivipera wagneri venom

PurposeThis study aims to measure the paraspecific neutralization capacity of nationally produced HSGM polyvalent snake antivenom (HSGM-PSAV), produced using Macrovipera lebetina obtusa, Montivipera xanthina, and Vipera ammodytes montandoni venom, against the lethal effect of the venom of Montivipera wagneri, which is endemic to the Eastern Black Sea and Eastern Anatolia regions of Turkey. MethodsThe neutralization capacity of HSGM-PSAV against the lethal effect of M. wagneri venom was studied using the potency determination testing method specified in the Turkish and European Pharmacopoeia. Lethal dose 50 (LD50) values of the venoms used in immunization, M. wagneri venom in mice, and effective dose 50 (ED50) values of HSGM-PSAV against four types of venoms were calculated using two-fold dilutions. ResultsHSGM-PSAV neutralized the lethal effect of M. wagneri venom in mice. The ED50 of the HSGM-PSAV against M. wagneri venom was calculated as 304.42 LD50/mL. ConclusionAs a result of this in-vivo study, it was determined that HSGM-PSAV neutralized M.wagneri venom above the antivenom neutralization capacity threshold values (≥50 LD50/mL) specified in the Turkish and European Pharmacopoeia. This result is important preclinical data regarding the usability of HSGM-PSAV in the treatment of poisoning due to M. wagneri bites.

Enhancing linezolid activity in the treatment of oral biofilms using novel chitosan microneedles with iontophoretic control

This study aimed to prepare and assess active microneedle (MN) patches based on a novel biomaterial and their effective coupled (physical and electrical) transdermal delivery of a model drug (Linezoid). Modified MN patches (e.g. fabricated from Linezoid, boronated chitosan, polyvinyl alcohol and D-sorbitol) were engineered using a vacuum micromoulding method. Physicochemical, FTIR (Fourier transform infrared), in-silico, structural and thermal analysis of prepared formulations were conducted to ascertain MN quality, composition and integrity. In-vitro mechanical tests, membrane toxicity, drug release, antibiofilm, ex-vivo mucoadhesion, insertion and in-vivo antibiofilm studies were performed to further validate viability of the coupled system. Optimized MN patch formulation (CSHP3 - comprising of 3 % w/v boronated chitosan, 3.5 % w/v PVA and 10 % w/w D-sorbitol) exhibited sharp-tipped, equi-distant and uniform-surfaced micron-scaled projections with conforming physicochemical features. FTIR analysis confirmed modification (i.e., boronation) of chitosan and compatibility as well as interaction between CSHP3 constituents. In-silico analysis indicated non-covalent interactions between all formulation constituents. Moreover, boronated chitosan-mucin glycoprotein complex showed a stronger bonding (∼1.86 times higher CScore) as compared to linezolid-mucin counterpart. Thermal analysis indicated amorphous nature of CSHP3. A ∼ 1.42 times higher tensile strength was displayed by CSHP3 as compared to control (i.e., pure chitosan, polyvinyl alcohol and D-sorbitol-based MN patch). Membrane toxicity study indicated non-toxic and physiological compatible nature of CSHP3. Within 90 min, 91.99 ± 2.3 % linezolid was released from CSHP3. During release study on agarose gel, CSHP3-iontophoresis treatment resulted in a ∼ 1.78 and ∼ 1.20 times higher methylene blue-covered area and optical density, respectively, within 60 min as compared to CSHP3 treatment alone. Staphylococcus aureus biofilms treated with CSHP3 exhibited 65 ± 4.2 % reduction in their mass. CSHP3 MN patches remained adhered to the rabbit oral mucosa for 6 ± 0.15 h. Mucosa treated with CSHP3 and CSHP3-iontophoresis combination showed a generation of pathways in the epithelium layers without any damage to the underlying lamina propria. Eradication of Staphylococcus aureus from oral mucosal wounds and complete tissue regeneration was recorded following 7-day treatment using CSHP3-iontophoresis coupled approach.