Semaglutide in Heart Failure: A Systematic Review of Outcomes of Semaglutide in Heart Failure Patients.

Heart failure (HF) stands as a formidable challenge in global healthcare casting a long shadow over both morbidity and mortality. A significant interplay between HF and type 2 diabetes (T2DM) manifests an elevated risk of adverse cardiovascular events in T2DM patients. Glucagon-like peptide 1 emerges as a pivotal player in T2DM, which is released in response to meals rich in glucose and lipids. We aim to assess the outcomes of using semaglutide in HF. A comprehensive literature search was performed using electronic databases, including PubMed/Medline, the Cochrane Library, and Google Scholar, covering all records up to May 10, 2024. Studies meeting inclusion criteria were selected. Qualitative analysis was conducted to analyze the findings of the studies included. Four studies (three randomized controlled trials and one observational study) were included in our manuscript. There was a significant decrease in the Kansas City Cardiomyopathy Questionnaire clinical summary score (p< 0.001), body weight (p< 0.001), six-minute walk distance (p< 0.001), and CRP levels (p< 0.001). A statistically significant decrease in overall major adverse cardiac events was observed with a hazard ratio of 0.76 (95% CI 0.62, 0.92). Other factors and adverse effects were also discussed in our manuscript. Our study showed that semaglutide resulted in improvement in HF patients. Although adverse effects were observed, they were not as significant as the placebo itself.

Unveiling Breakthroughs in Post-resuscitation Supportive Care for Out-of-Hospital Cardiac Arrest Survivors: A Narrative Review.

Survivors of out-of-hospital cardiac arrest (OHCA) experience significant mortality rates and neurological impairment, potentially attributed to the hypoxic-ischemic injury sustained amid the cardiac arrest episode. Post-resuscitation care plays a crucial role in determining outcomes for survivors of OHCA. Supportive therapies have proven to be influential in shaping these outcomes. However, targeting higher blood pressure or oxygen levels during the post-resuscitative phase has not been shown to offer any mortality or neurological benefits. In terms of maintaining hemodynamic instability after resuscitation, it is recommended to use norepinephrine rather than epinephrine. While extracorporeal cardiopulmonary resuscitation has shown promising results, targeted temperature management has been found ineffective in improving outcomes despite its previous potential. This review also investigates various challenges and barriers associated with the practical implementation of these supportive therapies in clinical settings. The review also highlights areas ripe for future research and proposes potential directions to further enhance post-resuscitation supportive care for OHCA survivors.

Therapeutic Application of Microsponges-based Drug Delivery Systems.

Microsponges delivery systems (MDS) are highly porous, cross-linked polymeric systems that activate due to temperature, pH, or when rubbed. MDS offer a wide range of advantages, like controlled drug release, site-specific action, stability over a broad range of pH, less irritation, cost-effectiveness, and improved patient compliance. They can be transformed into various dosage forms like creams, gels, and lotions. MDS are suitable for the treatment of topical disorders like acne, psoriasis, dandruff, eczema, scleroderma, hair loss, skin cancer, and other dreadful diseases. The applications of MDS in drug delivery are not limited to topical drug delivery but are also explored for oral, parenteral, and pulmonary drug deliveries. Microsponges have been studied for colon targeting of drugs and genes. Additionally, MDS have several applications such as sunscreen, cosmetics, and over-the-counter (OTC) products. Furthermore, MDS do not actuate any irritation, genotoxicity, immunogenicity, or cytotoxicity. Therefore, this review extensively highlights microsponges, their advantages, key factors affecting their characteristics, their therapeutic applications in topical disorders and in cancer, their use as cosmetics, as well as recent advances in MDS and the associated challenges.

Development of a Validated Bioanalytical UPLC-MS/MS Method for Quantification of Neratinib: A Recent Application to Pharmacokinetic Studies in Rat Plasma.

Neratinib, a tyrosine kinase inhibitor, was very recently approved by USFDA in 2017 as an anticancer drug to treat of HER2 positive breast cancers. The present work provides an account on the development of a validated bioanalytical UPLC-MS/MS method for quantification of neratinib and internal standard (imatinib) in rat plasma and tissue homogenates. A UPLC having a 100 mm C18 column (1.7 µm sized particles) was used with acetonitrile (0.1% formic acid): 2 mMol of ammonium acetate in water (pH 3.5) as the mobile phase. An efficient chromatographic separation was performed and detection was achieved by monitoring precursor-to-product ion transitions with m/z 557.29 â†’ 112.06 for neratinib and m/z 494.43 â†’ 294.17 for IS. The method demonstrated excellent linearity in the spiked plasma drug concentrating ranging between 1 and 800 ng.mL-1 (r2 = 0999), with lower limit of quantification (LLOQ) was observed at 1 ng.mL-1. Intra-assay and inter-assay precision relative standard deviations were found to be within 6.58. Mean extraction recovery for neratinib and IS were 99.44 and 99.33%, while matrix effect for neratinib and IS was ranging between -4.35 and - 3.66%, respectively. Overall, the method showed successful applicability in pharmacokinetic analysis of pure various formulations in Wistar rat plasma.

Crotamiton-loaded tea tree oil containing phospholipid-based microemulsion hydrogel for scabies treatment: in vitro, in vivo evaluation, and dermatokinetic studies.

Crotamiton (CRT) is a commonly approved drug prescribed for the scabies treatment in many countries across the globe. However, poor aqueous solubility and low bioavailability, and side effects restrict its use. To avoid such issues, an appropriate carrier system is necessary which can address the aforementioned challenges for attaining enhanced biopharmaceutical attributes. The current study intends to provide a detailed account on the development and evaluation of CRT-loaded microemulsion (ME) hydrogel formulation containing tea tree oil (TTO) for improved drug delivery for scabies treatment in a safe and effective manner. Pseudo-ternary phase diagrams were constructed with TTO as the oily phase, and Cremophor®EL was used as the surfactant in a mass ratio 2:1 with co-surfactants (mixture of phospholipid 90G and Transcutol®P), and aqueous solution as the external phase. The optimized drug-loaded ME formulation was evaluated for skin penetration, retention, compliance, and dermatokinetics. The nonirritant behavior of the formulation was revealed by skin histopathology, which showed no changes in normal skin histology. In comparison to the conventional product, dermatokinetic experiments revealed that CRT has greater penetration and distribution in the epidermis of the mice skin. The findings imply that the proposed lipid-based ME hydrogel can aid in the resolution of CRT issues by providing a better and safer delivery option to epidermis and deeper epidermis in substantial quantities.

Three 'D's: Design approach, dimensional printing, and drug delivery systems as promising tools in healthcare applications.

The development of pharmaceutical drug products is required for the treatment of disease, which has resulted in an increasing number of approvals by regulatory agencies across the globe. To establish a hassle-free manufacturing process, the systematic use of a quality-by-design (QbD) approach combined with process analytical technology (PAT) and printing techniques can revolutionize healthcare applications. Printing technology has been emerged in various dimensions, such as 3D, 4D, and 5D printing, with respect to their production capabilities, durability, and accuracy of pharmaceutical manufacturing, which can efficiently deliver novel patient-centric healthcare products with holistic characteristics. In this review, we provide current trends in pharmaceutical product development using a design approach and high-quality printing techniques.

Systematic development of lectin conjugated microspheres for nose-to-brain delivery of rivastigmine for the treatment of Alzheimer's disease.

The current study focuses on development of nasal mucoadhesive microspheres for nose-to-brain delivery of rivastigmine for Alzheimer treatment. A systematic development was employed for optimization of the formulation and process parameters influential on the quality attributes of the microspheres. The risk assessment study revealed major influence of the polymer concentration (ethylcellulose: chitosan), the concentration of surfactant solution (polyvinyl alcohol), and stirring speed as the critical factors for optimization of the microspheres. These factors were systematically optimized using Box-Behnken design and microspheres were evaluated for the particle size, entrapment efficiency, and in vitro drug release as the response variables. The optimized microspheres containing 4.4% wt/vol polymers, 1% wt/vol surfactant, and stirring speed at 1500 rpm showed particle size of 19.9 µm, entrapment efficiency of 77.8%, and drug release parameters as T80% of 7.3 h. The surface modification of microspheres was performed with lectin by carbodiimide activation reaction and confirmed by difference in surface charge before and after chemical functionalization by zeta potential measurement which was found to be - 25.7 mV and 20.5 mV, respectively. Ex vivo study for bioadhesion strength evaluation on goat nasal mucosa indicated a significant difference (p < 0.001) between the plain (29%) and lectin functionalized microspheres (64%). In vivo behavioral and biochemical studies in the rats treated with lectin functionalized microspheres showed markedly better memory-retention vis-à-vis test and pure drug solution treated rats (p < 0.001). In a nutshell, the present studies showed successful development of nasal microspheres for enhanced brain delivery of rivastigmine for Alzheimer's treatment.

In Vivo Pharmacological Testing of Herbal Drugs for Anti-Allergic and Anti-Asthmatic Properties.

Background: Asthma is a chronic inflammatory disease characterized by reversible airway obstruction, hyperresponsiveness, and remodeling. Asthma prevalence has increased significantly globally over the last decade, and it remains incurable to this date. Aims and Objectives: The present study evaluated some of the antiasthmatic medicinal plants to assess their mode of action. Materials and Method: Animal models for milk-induced leukocytosis, milk-induced eosinophilia, mast cell degranulation, clonidine-induced catalepsy, and active paw anaphylaxis were used to assess the pharmacological effects of Ammi visnaga, Medicago sativa, and Urtica dioica. Results: Mice pretreated with diazepam, methanolic extract of M. sativa, and U. dioica exhibited significant (P < 0.05) inhibition in milk-induced leukocytosis. However, only M. sativa showed statistically significant (P < 0.05) results. All plants showed a statistically significant (P < 0.05) tendency to decrease milk-induced eosinophilia. Methanolic extracts of all plants significantly (P < 0.05) protected mast cells against degranulation by clonidine. A. visnaga and U. dioica significantly (P < 0.05) protected mice against clonidine-induced catalepsy. An acute treatment by M. sativa potentiated the catalepsy, while it significantly inhibited the catalepsy (P < 0.05) upon chronic treatment. In the allergic inflammation model, methanolic extracts of all plants under study decreased paw thickness in a statistically significant manner (P < 0.05). Conclusion: All the three plants in this study demonstrated anti-inflammatory and antihistaminic effects, as well as decreased paw thickness, validate anti-allergic properties. A. visnaga showed a mast cell-stabilizing effect. A. visnaga and U. dioica inhibited the histamine-mediated clonidine-induced catalepsy from mast cells which proves the antihistaminic activity of these plants.

The Development of Pemetrexed Diacid-Loaded Gelatin-Cloisite 30B (MMT) Nanocomposite for Improved Oral Efficacy Against Cancer: Characterization, In-Vitro and Ex-Vivo Assessment.

AIM: The intention of this investigation was to develop Pemetrexed Diacid (PTX)-loaded gelatine-cloisite 30B (MMT) nanocomposite for the potential oral delivery of PTX and the in vitro, and ex vivo assessment. BACKGROUND: Gelatin/Cloisite 30 B (MMT) nanocomposites were prepared by blending gelatin with MMT in aqueous solution. METHODS: PTX was incorporated into the nanocomposite preparation. The nanocomposites were investigated by Fourier Transmission Infra Red Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscope (SEM) X-Ray Diffraction (XRD) and Confocal Laser Microscopy (CLSM). FT-IR of nanocomposite showed the disappearance of all major peaks which corroborated the formation of nanocomposites. The nanocomposites were found to have a particle size of 121.9 ± 1.85 nm and zeta potential -12.1 ± 0.63 mV. DSC thermogram of drug loaded nanocomposites indicated peak at 117.165 oC and 205.816 oC, which clearly revealed that the drug has been incorporated into the nanocomposite because of cross-linking of cloisite 30 B and gelatin in the presence of glutaraldehyde. RESULTS: SEM images of gelatin show a network like structure which disappears in the nanocomposite. The kinetics of the drug release was studied in order to ascertain the type of release mechanism. The drug release from nanocomposites was in a controlled manner, followed by first-order kinetics and the drug release mechanism was found to be of Fickian type. CONCLUSION: Ex vivo gut permeation studies revealed 4 times enhancement in the permeation of drug present in the nanocomposite as compared to plain drug solution and were further affirmed by CLSM. Thus, gelatin/(MMT) nanocomposite could be promising for the oral delivery of PTX in cancer therapy and future prospects for the industrial pharmacy.

Optimisation of ethosomal nanogel for topical nano-CUR and sulphoraphane delivery in effective skin cancer therapy.

Aim: The optimisation and evaluation of ethosomal nanogel (NGs) for topical delivery in skin cancer.Methods: The formulations were optimised by employing 3-factor, 3-level Box Behnken design for responses of vesicle size, and fluxes. They characterised in vitro and evaluated for drug release, permeation and retention, skin penetration of ethosome, electron microscopy, texture analysis, and in vitro cytotoxicity.Results: The optimised formulation exhibited z-average 125.67 ± 10.43 nm, apparent zeta potential -17.1 ± 2.61 mV, average flux of drug loaded ethosome were 54.72 ± 5.45 and 59.83 ± 6.09 µg/cm2/h. Further, Rhodamine B loaded ethosome penetrated deeper up to 183.82 µm. The NGs texture analysis showed index of viscosity 225.45 g.s, firmness 209.34 g, cohesiveness -189.48 g, and consistency 59.45 g.s. The optimised ethosome NGs exhibited significant anti-cancer effect in B16-F10 murine tumour cell line (p < 0.05).Conclusion: Ethosomal NGs could be promising for skin cancer treatment.

Sulforaphane-decorated gold nanoparticle for anti-cancer activity: in vitro and in vivo studies.

This study aims to develop sulforaphane-loaded gold nanoparticles (SFN-GNPs) as a potential nanomedicine against the solid tumors. Citrate-mediated electrolysis optimized by four-factor three-level Box-Behnken experimental design was used to get nanoparticles of size <200 nm. The formulation was characterized and evaluated for cytotoxicity B16-F10, MCF-7, SW-620 and Caco-2 cell line. Single dose oral pharmacokinetics, gamma scintigraphy-based bio-distribution and tumor regression studies were conducted to evaluate the in vivo performance. Optimized SFN-GNPs showed spherical morphology with a particle size of 147.23 ± 5.321 nm, the zeta potential of -12.7 ± 1.73 mV, entrapment efficiency of 83.17 ± 3.14% and percentage drug loading of 37.26 ± 2.33%. With SFN-GNPs, both SFN (75.99 ± 2.36%) and gold (58.11 ± 2.48%) were able to permeate through the intestinal wall in 48 h. SFN-GNPs were able to bring LC50 of <100 µg/ml in all the cytotoxicity assays, more than 5-fold increase in AUC0-t, enhanced retention at tumor site as well as significant pre-induction tumor growth inhibition and post-induction tumor reduction as compared to plain SFN solution.

Development and optimization of sulforaphane-loaded nanostructured lipid carriers by the Box-Behnken design for improved oral efficacy against cancer: in vitro, ex vivo and in vivo assessments.

In the present study, sulforaphane (SFN)-loaded nanostructured lipid carriers (NLC) were developed and optimized for improved oral efficacy against cancer. The SFN-loaded NLC formulation was developed by melt emulsification ultrasonication technique and optimized by Box-Behnken statistical design. The optimized SFN-loaded NLC formulation composed of precirol® ATO 5 (solid lipid) and vitamin E (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and Tween 80 (1%) as surfactant. The mean particle size, polydispersity index, zeta potential, entrapment efficiency (%) and drug loading (%) of optimized SFN-loaded NLC formulation was observed to be 145.38 ± 4.46 nm, 0.181 ± 0.023, -25.12 ± 2.36 mV, 84.94 ± 3.82% and 14.82 ± 3.46%, respectively. In vitro drug release studies showed that the release of SFN from optimized NLC formulation was significantly higher (86.52 ± 5.48%) compared to SFN suspension (38.47 ± 5.52%) up to 24 h. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the NLC compared to plain SFN solution and were further confirmed by CLSM. MTT assay in different cancer cell lines showed that the optimized SFN-loaded NLC formulation exhibited significantly improved (p < .05) cytotoxicity compared to free SFN solution. SFN-loaded NLC formulation showed significantly improved antioxidant activity compared to free SFN solution. Furthermore, pharmacokinetic study on albino Wistar rats showed 5.04-fold increase in relative oral bioavailability with NLC (p < .05) compared to SFN suspension. Therefore, NLC represents a great potential for improved efficacy of SFN after oral administration.

Lipid drug conjugate nanoparticle as a potential nanocarrier for the oral delivery of pemetrexed diacid: Formulation design, characterization, ex vivo, and in vivo assessment.

The present work was to develop lipid drug conjugated (LDC) nanoparticles for the potential oral delivery of pemetrexed diacid (PTX) and evaluation of its in vitro, ex vivo and in vivo potentials. The LDC was prepared by salt formation of PTX with stearic acid and followed by cold homogenization technique to produce the LDC nanoparticles. FTIR analysis of LDC proved the presence of amide bond in LDC powder indicating the conjugation between drug and lipid. LDC nanoparticles was found to have particle size 121.9±1.85nm and zeta potential -51.6mV±1.23 and entrapment efficiency 81.0±0.89%. TEM images revealed spherical morphology and were in corroboration with particle size measurements. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the LDC as compared to plain drug solution and were confirmed by CLSM. MTT assay conformed significant% toxicity at the end of 24h and 48h. Furthermore, the AUC0-24 of PTX from the optimized LDC nanoparticels was found to be 4.22 folds higher than that from PTX suspension on oral administration. Thus, LDC has high potential for the oral delivery of PTX in cancer therapy and future prospects for the industrial purpose.