Revolutionizing Cancer Treatment: Biopolymer-Based Aerogels as Smart Platforms for Targeted Drug Delivery.

Cancer stands as a leading cause of global mortality, with chemotherapy being a pivotal treatment approach, either alone or in conjunction with other therapies. The primary goal of these therapies is to inhibit the growth of cancer cells specifically, while minimizing harm to healthy dividing cells. Conventional treatments, often causing patient discomfort due to side effects, have led researchers to explore innovative, targeted cancer cell therapies. Thus, biopolymer-based aerogels emerge as innovative platforms, showcasing unique properties that respond intelligently to diverse stimuli. This responsiveness enables precise control over the release of anticancer drugs, enhancing therapeutic outcomes. The significance of these aerogels lies in their ability to offer targeted drug delivery with increased efficacy, biocompatibility, and a high drug payload. In this comprehensive review, the author discuss the role of biopolymer-based aerogels as an emerging functionalized platforms in anticancer drug delivery. The review addresses the unique properties of biopolymer-based aerogels showing their smart behavior in responding to different stimuli including temperature, pH, magnetic and redox potential to control anticancer drug release. Finally, the review discusses the application of different biopolymer-based aerogel in delivering different anticancer drugs and also discusses the potential of these platforms in gene delivery applications.

Anticancer Effects of New Ceramides Isolated from the Red Sea Red Algae Hypnea musciformis in a Model of Ehrlich Ascites Carcinoma: LC-HRMS Analysis Profile and Molecular Modeling.

Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids-docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid 6-as well as three ceramides-A (1), B (2), and C (3)-with 9-methyl-sphinga-4,8-dienes and phytosphingosine bases. Additionally, different phytochemicals were determined using the liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS) technique. Ceramides A (1) and B (2) exhibited promising in vitro cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line when compared with doxorubicin as a positive control. Further in vivo study and biochemical estimation in a mouse model of Ehrlich ascites carcinoma (EAC) revealed that both ceramides A (1) and B (2) at doses of 1 and 2 mg/kg, respectively, significantly decreased the tumor size in mice inoculated with EAC cells. The higher dose (2 mg/kg) of ceramide B (2) particularly expressed the most pronounced decrease in serum levels of vascular endothelial growth factor -B (VEGF-B) and tumor necrosis factor-α (TNF-α) markers, as well as the expression levels of the growth factor midkine in tumor tissue relative to the EAC control group. The highest expression of apoptotic factors, p53, Bax, and caspase 3 was observed in the same group that received 2 mg/kg of ceramide B (2). Molecular docking simulations suggested that ceramides A (1) and B (2) could bind in the deep grove between the H2 helix and the Ser240-P250 loop of p53, preventing its interaction with MDM2 and leading to its accumulation. In conclusion, this study reports the cytotoxic, apoptotic, and antiangiogenic effects of ceramides isolated from the Red Sea algae Hypnea musciformis in an experimental model of EAC.

Chitosan-TPP nanoparticles stabilized by poloxamer for controlling the release and enhancing the bioavailability of doxazosin mesylate: in vitro, and in vivo evaluation.

Objective: Control the release and enhance the bioavailability of chitosan-doxazosin mesylate nanoparticles (DM-NPs). Significance: Improve DM bioavailability for the treatment of benign prostatic hyperplasia and hypertension. Methods: Plackett-Burman design was utilized to screen the variables affecting the quality of DM-NPs prepared by ionic gelation method. The investigated variables were initial drug load (X1), chitosan percentage (X2), tripolyphosphate sodium (TPP) percentage (X3), poloxamer percentage (X4), homogenization speed (X5), homogenization time (X6) and TPP addition rate (X7). The prepared DM-loaded NPs have been fully evaluated for particle size (Y1), Zeta potential (Y2), production yield (Y3), entrapment efficiency (Y4), loading capacity (Y5), initial burst (Y6), and cumulative drug release (Y7). Finally, DM pharmacokinetic has been investigated on healthy albino male rabbits by means of non-compartmental analysis. Results: The combination of variables showed variability of Y1, Y2, and Y3 equal to 122-710 nm, 3.49-23.63 mV, and 47.31-92.96%, respectively. While Y4 and Y5, reached 99.87%, and 8.53%, respectively. The prepared NPs revealed that X2, X3, and X4 are the variables that play the important role in controlling the release behavior of DM from the NPs. The in vivo pharmacokinetic results indicated the enhancement in bioavailability of DM by 7 folds compared to drug suspension and the mean residence time prolonged to 23.72 h compared to 4.7 h of drug suspension. Conclusion: The study proved that controlling the release of DM from NPs enhance its bioavailability and improve the compliance of patients with hypertension or benign prostatic hyperplasia.

Preparation, Optimization, and Evaluation of Hyaluronic Acid-Based Hydrogel Loaded with Miconazole Self-Nanoemulsion for the Treatment of Oral Thrush.

Miconazole nitrate (MZ) is a BCS class II antifungal poorly water-soluble drug with limited dissolution properties and gastrointestinal side effects. Self-nanoemulsifying delivery system-based gel of MZ can improve both solubility and oral mucosal absorption with enhanced antifungal activity. The study aims to formulate MZ self-nanoemulsion (MZ-NE) and combine it within hyaluronic acid-based gel. MZ solubility in various oils, surfactants, and cosurfactant used in NE formulations were evaluated. Mixture design was implemented to optimize the levels of NE components as a formulation variable to study their effects on the mean globule size and antifungal inhibition zones. Further, the optimized MZ-NE was loaded into a hyaluronic acid gel base. Rheological behavior of the prepared gel was assessed. Ex vivo permeability of optimized formulation across buccal mucous of sheep and inhibition against Candida albicans were examined. Mixture design was used to optimize the composition of MZ-NE formulation as 22, 67, and 10% for clove oil, Labrasol, and propylene glycol, respectively. The optimized formulation indicated globule size of 113 nm with 29 mm inhibition zone. Pseudoplastic flow with thixotropic behavior was observed, which is desirable for oral gels. The optimized formulation exhibited higher ex vivo skin permeability and enhanced antifungal activity by 1.85 and 2.179, respectively, compared to MZ-SNEDDS, and by 1.52 and 1.72 folds, respectively, compared to marketed gel. Optimized MZ-NE hyaluronic acid-based oral gel demonstrated better antifungal activity, indicating its potential in oral thrush pharmacotherapy.

Clinical pharmacokinetic study for the effect of glimepiride matrix tablets developed by quality by design concept.

OBJECTIVE: Implementation of a new pharmaceutical technique to improve aqueous solubility and thus dissolution, enhancement of drug permeation, and finally formulation of a controlled release tablet loaded with glimepiride (GLMP). SIGNIFICANCE: Improve GLMP bioavailability and pharmacokinetics in type II diabetic patients. METHODS: Different polymers were used to enhance aqueous GLMP solubility of which a saturated polymeric drug solution was prepared and physically adsorbed onto silica. An experimental design was employed to optimize the formulation parameters affecting the preparation of GLMP matrix tablets. A compatibility study was conducted to study components interactions. Scanning electron microscope (SEM) was performed before and after the tablets were placed in the dissolution medium. An in vivo study in human volunteers was performed with the optimized GLMP tablets, which were compared to pure and marketed drug products. RESULTS: Enhancement of GLMP aqueous solubility, using the polymeric drug solution technique, by more than 6-7 times when compared with the binary system. All the studied formulation factors significantly affected the studied variables. No significant interaction was detected among components. SEM illustrated the surface and inner tablet structure, and confirmed the drug release which was attributed to diffusion mechanism. The volunteer group administered the optimized GLMP tablet exhibited higher drug plasma concentration (147.4 ng/mL), longer time to reach maximum plasma concentration (4 h) and longer t1/2 (7.236 h) compared to other groups. CONCLUSIONS: Matrix tablet loaded with a physically modified drug form could represent a key solution for drugs with inconsistent dissolution and absorption profiles.

Development of optimized self-nanoemulsifying lyophilized tablets (SNELTs) to improve finasteride clinical pharmacokinetic behavior.

OBJECTIVE: Preparation of an optimized finasteride (FSD) lyophilized tablets loaded with self-nanoemulsifying drug delivery system (SNEDDS). SIGNIFICANCE: Enhance FSD bioavailability in male pattern baldness and benign prostatic hyperplasia. METHODS: Two-step optimization was implemented to achieve the study goals. First; the mixture design was used to develop an optimized SNEDDS through which the effect of cosurfactant number of carbon atoms on SNEDDS particle size and thermodynamic stability has been tested. Second; the different tablet excipients have been used to develop an optimized self-nanoemulsifying lyophilized tablets (SNELTs). The prepared tablets have been fully characterized. Interaction among tablet components has been studied. Finally, FSD clinical pharmacokinetic has been investigated on human volunteers. RESULTS: Anise oil and tween 80 were selected as oily phase and surfactant, respectively while different aliphatic alcohols were studied as cosurfactants. Percentages of oil, surfactant, and cosurfactants were significantly affecting SNEDDS particle size. Increasing cosurfactant number of carbon atoms achieved smaller particle size and higher stability. The optimized SNEDDS was found to contain 10.3455, 45.8972, and 43.7573% of anise oil, tween 80, and butanol, respectively. Variations in FSD cumulative release and disintegration time, from the prepared tablets, were attributed to change in the percent of plasdone XL, Avicel and silica. No interaction among components was noticed. Clinical pharmacokinetics illustrated significant enhancement in the studied parameters from the optimized lyophilized tablets loaded with drug SNEDDS when compared to marketed FSD product. CONCLUSION: Lyophilized tablets could be considered as a good alternative for conventional solid dosage forms especially when loaded with drug nanosystems.

Zein based magnesium oxide nanoparticles: Assessment of antimicrobial activity for dental implications.

MgO nanoparticles have been recently discovered as an antibacterial, however, they limited by property degradation due to agglomeration. The addition of a coating agent, such as a zein polymer, is effective in preventing agglomeration without affecting nanosized properties. The aim of this study was to assess the antimicrobial property of MgO nanoparticles when coated with a zein polymer against several oral bacteria and fungi. This was done by utilizing various assessment techniques. The ultimate aim is to use these nanoparticles in dental preparations. The antimicrobial activity of zein-coated MgO nanoparticles at different concentrations of 0.5, 1 and 2% were tested against four different microorganisms: Staphylococcus aureus, Streptococcus mutans and Enterococcus faecalis (gram positive bacteria), and Candida albicans (as oral fungus). Two different techniques were utilized: the Kirby-Bauer test, and a modified direct contact test. The results indicated that the antibacterial effect of 1% or 2% zein-coated MgO nanowires were statistically significant (p<0.05) against the four organisms studied: S. mutans, S. aureus, E. faecalis and C. albicans. Zein-coated MgO nanoparticles are a new human friendly and potent antimicrobial agent that can be incorporated in the formulation of a variety of new dental materials and products that should provide improvements in dental care and oral health.

Controlled release of injectable liposomal in situ gel loaded with recombinant human bone morphogenetic protein-2 for the repair of alveolar bone clefts in rabbits.

BACKGROUND AND OBJECTIVE: The aim of the present study was to develop and examine a new non-invasive injectable graft for the repair of alveolar bone clefts using recombinant human bone morphogenetic protein-2 (rhBMP-2) encapsulated within injectable liposomal in situ gel (LIG). METHOD: Different liposomal formulations loaded with rhBMP-2 were prepared, and the effects of the preparation methods and lipid content on the efficiency of rhBMP-2 encapsulation within the liposomes were studied. For the preparation of in situ gel, deacetylated gellan gum (DGG) was used, and the in vitro gelation characteristics of the gel were evaluated. In vivo pharmacokinetics and histology were also assessed. Critical size alveolar defects were surgically created in the maxillae of 30 New Zealand rabbits and treated with different injectable formulae, including rhBMP-2 liposomes and in situ gel (rhBMP-2-LIG). RESULTS: The results indicated that the prepared rhBMP-2-LIG prolonged the release and residence time of BMP-2 within rabbits for more than 7 days. Histomorphometric assessment showed 67% trabecular bone filling of the defects treated using this novel formula. CONCLUSION: BMP-2-LIG is a promising delivery device for the repair of alveolar bone defects associated with cleft deformities.

Statistical optimization of controlled release microspheres containing cetirizine hydrochloride as a model for water soluble drugs.

The purpose was to improve the encapsulation efficiency of cetirizine hydrochloride (CTZ) microspheres as a model for water soluble drugs and control its release by applying response surface methodology. A 3(3) Box-Behnken design was used to determine the effect of drug/polymer ratio (X1), surfactant concentration (X2) and stirring speed (X3), on the mean particle size (Y1), percentage encapsulation efficiency (Y2) and cumulative percent drug released for 12 h (Y3). Emulsion solvent evaporation (ESE) technique was applied utilizing Eudragit RS100 as coating polymer and span 80 as surfactant. All formulations were evaluated for micromeritic properties and morphologically characterized by scanning electron microscopy (SEM). The relative bioavailability of the optimized microspheres was compared with CTZ marketed product after oral administration on healthy human volunteers using a double blind, randomized, cross-over design. The results revealed that the mean particle sizes of the microspheres ranged from 62 to 348 µm and the efficiency of entrapment ranged from 36.3% to 70.1%. The optimized CTZ microspheres exhibited a slow and controlled release over 12 h. The pharmacokinetic data of optimized CTZ microspheres showed prolonged tmax, decreased Cmax and AUC0-∞ value of 3309 ± 211 ng h/ml indicating improved relative bioavailability by 169.4% compared with marketed tablets.

Development and evaluation of avanafil self-nanoemulsifying drug delivery system with rapid onset of action and enhanced bioavailability.

Utilization of lipid-based drug delivery systems has recently gained focus for drugs characterized by poor aqueous solubility. The improved aqueous solubility overcomes one of the main barriers that limit their bioavailability. The objective of this work was to improve the solubility and oral bioavailability of Avanafil (AVA), a recently approved second generation type 5 phospodiesterase inhibitor used for erectile dysfunction.AVA was formulated as self-nanoemulsifying drug delivery system (SNEDDS) utilizing various oils, surfactants, and cosurfactants. The solubility of AVA in various oils, surfactants, and cosurfactants was determined. Ternary phase diagram was constructed to identify stable nanoemulsion region. The prepared AVA loaded SNEDDS were assessed for optical clarity, droplet size, conductivity, and stability studies. In vitro drug release and in vivo pharmacokinetic parameters using animal model were also investigated. Results revealed that stable AVA (SNEDDS) were successfully developed with a droplet size range of 65 to 190 nm. SNEDDS composed of 25% dill oil, 55% Tween 80, and 20% propylene glycol successfully improved solubilization of AVA (over 80% within 30 min) vis-a-vis the powder AVA (35% within 30 min). In vivo pharmacokinetic showed a significant (P < 0.05) increase in Cmax, reduction in Tmax, and SNEDDS enhanced the bioavailability in the rats by 1.4-fold when compared with pure drug.

Utilization of nanotechnology and experimental design in the development and optimization of a posaconazole‒calendula oil nanoemulgel for the treatment of mouth disorders.

Introduction: Essential oil‒based nanoemulsions (NEs) are the subjects of extensive investigation due to their potential to address a variety of oral health issues. NEs are delivery systems that improve lipid medicine solubility and distribution to intended sites. The goal of the current study was to create and enhance a self-nanoemulsifying drug delivery paradigm based on calendula oil (CO) and decorated with chitosan (CS) that could deliver posaconazole (PSZ) for the treatment of gingivitis. Method: Employing a response-surface Box‒Behnken design, PSZ-CO-CS NEs were created with varying amounts of PSZ (10, 15, and 20 mg), percentages of CO (6%, 12%, and 18%), and percentages of CS (0.5%, 1.5%, and 2.5%). Results and conclusion: The optimized formulation resulted in a 22-mm bacterial growth suppression zone, 25-mm fungal growth inhibition zone, droplet sizes of 110 nm, and a viscosity of 750 centipoise (cP). Using the appropriate design, the ideal formulation was produced; it contained 20 mg of PSZ, 18% of CO, and 1.35% of CS. Furthermore, the optimal formulation had a more controlled drug release, larger inhibition zones of bacterial and fungal growth, and desirable rheologic properties. Additionally, the optimized formulation substantially lowered the ulcer index in rats when tested against other formulations. Thus, this investigation showed that PSZ-CO-CS NEs could provide efficient protection against microbially induced gingivitis.

Novel enhancement of interfacial interaction and properties in biodegradable polymer composites using green chemically treated spent coffee ground microfiller.

This study investigates the potential of utilizing green chemically treated spent coffee grounds (SCGs) as micro biofiller reinforcement in Poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) biopolymer composites. The aim is to assess the impact of varying SCG concentrations (1 %, 3 %, 5 %, and 7 %) on the functional, thermal, mechanical properties and biodegradability of the resulting composites with a PHBV matrix. The samples were produced through melt compounding using a twin-screw extruder and compression molding. The findings indicate successful dispersion and distribution of SCGs microfiller into PHBV. Chemical treatment of SCG microfiller enhanced the interfacial bonding between the SCG and PHBV, evidenced by higher water contact angles of the biopolymer composites. Field Emission Scanning Electron Microscopy (FE-SEM) confirmed the successful interaction of treated SCG microfiller, contributing to enhanced mechanical characteristics. A two-way ANOVA was conducted for statistical analysis. Mass losses observed after burying the materials in natural soil indicated that the composites degraded faster than the pure PHBV polymer suggesting that both composites are biodegradable, particularly at high levels of spent coffee grounds (SCG). Despite the possibility of agglomeration at higher concentrations, SCG incorporation resulted in improved functional properties, positioning the green biopolymer composite as a promising material for sustainable packaging and diverse applications.

Fabrication and optimization of phospholipids-based phase separation in-situ gel loaded with BMP-2 nanosized emulsion for bone defect.

Introduction: The health, development, and/or survival of a newborn can be impacted by congenital abnormalities such as cleft lip (CLP) and palate, one of alveolar bone defects that emerge thru pregnancy. Therefore, the primary purpose of this study is to use phospholipids-based phase separation in-situ gel (PPSG) in combination with bone morphogenetic protein-2 nanoemulsion (BMP-2-NE) to aid repairing alveolar bone defects. Methods: To investigate how formulation parameters, such as the concentrations of BMP-2 aqueous solution, LauroglycolTM FCC, and Labrafac PG oil, affect NE qualities including droplet size and stability index, an l-optimal co-ordinate exchange statistical design was opted. Injectable PPSG with the best NE formulation was tested for viscosity characteristics, gel strength, water absorption, and in-vitro BMP-2 release. In rabbits, the percentage of BMP-2 that was still in the maxilla after 14 days was assessed. Results: Collected results revealed that the droplet size and stability index of optimal NE were discovered to be 68 2.0 nm and 96 1.3%, respectively. When mixed with water, optimal BMP-2 NE loaded PPSG became viscous and reached a gel strength of 41 s, which is adequate for injectable in-situ gels. In comparison to BMP-2 solution loaded in-situ gel, the in-vivo studies indicated that the newly created BMP-2 NE loaded PPSG produced a sustained and controlled release of BMP-2 that continued for 336 h (14 days). Further, 8% of the BMP-2 was still entrapped and not completely dissolved after 14 days, thus, created formulation allowed a higher percentage of BMP-2 to remain in rabbits' maxilla for longer time. Conclusion: PPSG that has been loaded with BMP-2 NE may therefore be a promising, fruitful, and less painful paradigm for the noninvasive therapy of CLP with significant effect and extended release.

Development and Optimization of a Novel Lozenge Containing a Metronidazole-Peppermint Oil-Tranexamic Acid Self-Nanoemulsified Delivery System to Be Used after Dental Extraction: In Vitro Evaluation and In Vivo Appraisal.

In-depth studies on essential oil-based nanoemulsions (NEs) have centered on a variety of oral health issues. NEs improve the delivery of nonpolar active agents to sites and thereby boost the dissolution and distribution of the agents. Metronidazole-peppermint oil-tranexamic acid self-nanoemulsifying drug delivery systems (MZ-PO-TX-SNEDDS) were created and loaded into novel lozenges to act as antifungal, hemostatic, antimicrobial, and analgesic dosage forms after dental extractions. The design-of-experiments approach was used in creating them. To generate the NEs, different concentrations of MZ-PO (240, 180, and 120 mg), 2% TX (600, 450, and 300 mg), and Smix1:1 (600, 400, and 200 mg) were used. The ideal formulation had serum levels of 1530 U/mL of interleukin-6, a minimal inhibitory concentration against bacteria of 1.5 µg/mL, a droplet size of 96 nm, and a blood coagulation time of 16.5 min. Moreover, the produced NE offered better MZ release. The adopted design was used to produce the ideal formulation; it contained 240 mg of MZ-PO, 600 mg of 2% TX, and 600 mg of Smix1:1. It was incorporated into lozenges with acceptable characteristics and an improved capability for drug release. These lozenges had reasonable coagulation times, IL-6 serum levels, and MIC values. All of these characteristics are desirable for managing symptoms following tooth extractions. Therefore, these lozenges loaded with MZ-PO-TX-SNEDDs might be considered a beneficial paradigm for relieving complications encountered after tooth extractions.

A Comprehensive Review: Epidemiological Strategies, Catheterization and Biomarkers used as a Bioweapon in Diagnosis and Management of Cardio Vascular Diseases.

Coronary artery disease (CAD) is a serious health problem that causes a considerable number of mortality in a number of affluent nations throughout the world. The estimated death encountered in many developed countries includes including Pakistan, reached 111,367 and accounted for 9.87% of all deaths, despite the mortality rate being around 7.2 million deaths per year, or 12% of all estimated deaths accounted annually around the globe, with improved health systems. Atherosclerosis progressing causes the coronary arteries to become partially or completely blocked, which results in CAD. Additionally, smoking, diabetes mellitus, homocystinuria, hypertension, obesity, hyperlipidemia, and psychological stress are risk factors for CAD. The symptoms of CAD include angina which is described as a burning, pain or discomfort in the chest, nausea, weakness, shortness of breath, lightheadedness, and pain or discomfort in the arms or shoulders. Atherosclerosis and thrombosis are the 2 pathophysiological pathways most frequently involved in acute coronary syndrome (ACS). Asymptomatic plaque disruption, plaque bleeding, symptomatic coronary blockage, and myocardial infarction are the prognoses for CAD. In this review, we will focus on medicated therapy which is being employed for the relief of angina linked with CAD including antiplatelet medicines, nitrates, calcium antagonists, blockers, catheterization, and the frequency of recanalized infarct-related arteries in patients with acute anterior wall myocardial infarction (AWMI). Furthermore, we have also enlightened the importance of biomarkers that are helpful in the diagnosis and management of CAD.

Production, optimization, and purification of alkaline thermotolerant protease from newly isolated Phalaris minor seeds.

The present work aims to purify and perform a preliminary analysis on a thermostable serine alkaline protease from a recently identified P. minor. The enzyme was purified 2.7-fold with a 12.4 % recovery using Sephadex G-100 chromatography, DEAE-cellulose, and ammonium sulphate precipitation. The isolated enzyme has a specific activity of 473 U/mg. The purified protease had a molecular mass of 29 kDa, and just one band was seen, which matched the band obtained using SDS-PAGE. High thermostability was demonstrated by the enzymes, which had half-lives of 31.79 and 6.0 min (a 5.3-fold improvement), enthalpies of denaturation (ΔH°) of 119.53 and 119.35 KJ mol-1, entropies of denaturation (ΔS°) of 32.96 and 41.11 J/mol·K, and free energies of denaturation (ΔG°) of 108.87 and 105.58 KJ mol-1 for the protease enzyme. Studies on the folding and stability of alkaline proteases are important since their use in biotechnology requires that they operate in settings of extreme pH and temperature. According to the kinetic and thermodynamic properties, the protease produced by P. minor is superior to that produced by other sources and previously described plants, and it might find utility in a variety of industrial fields.

Utilization of experimental design in the formulation and optimization of hyaluronic acid-based nanoemulgel loaded with a turmeric-curry leaf oil nanoemulsion for gingivitis.

Numerous problems affect oral health, and intensive research is focused on essential oil-based nanoemulsions that might treat prevent or these problems. Nanoemulsions are delivery systems that enhance the distribution and solubility of lipid medications to targeted locations. Turmeric (Tur)- and curry leaf oil (CrO)-based nanoemulsions (CrO-Tur-self-nanoemulsifying drug delivery systems [SNEDDS]) were developed with the goal of improving oral health and preventing or treating gingivitis. They could be valuable because of their antibacterial and anti-inflammatory capabilities. CrO-Tur-SNEDDS formulations were produced using the response surface Box-Behnken design with different concentrations of CrO (120, 180, and 250 mg), Tur (20, 35, and 50 mg), and Smix 2:1 (400, 500, and 600 mg). The optimized formulation had a bacterial growth inhibition zone of up to 20 mm, droplet size of less than 140 nm, drug-loading efficiency of 93%, and IL-6 serum levels of between 950 ± 10 and 3000 ± 25 U/ml. The optimal formulation, which contained 240 mg of CrO, 42.5 mg of Tur, and 600 mg of Smix 2:1, was created using the acceptable design. Additionally, the best CrO-Tur-SNEDDS formulation was incorporated into a hyaluronic acid gel, and thereafter it had improved ex-vivo transbuccal permeability, sustained in-vitro release of Tur, and large bacterial growth suppression zones. The optimal formulation loaded into an emulgel had lower levels of IL-6 in the serum than the other formulations evaluated in rats. Therefore, this investigation showed that a CrO-Tur-SNEDDS could provide strong protection against gingivitis caused by microbial infections.

Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation.

Mucoadhesive nanosized crystalline aggregates (NCs) can be delivered by the gastrointestinal, nasal, or pulmonary route to improve retention at particular sites. Itopride hydrochloride (ITH) was selected as a drug candidate due to its absorption from the upper gastrointestinal tract. For drug localization and target-specific actions, mucoadhesive polymers are essential. The current work aimed to use second-generation mucoadhesive polymers (i.e., thiolated polymers) to enhance mucoadhesive characteristics. An ITH-NC formulation was enhanced using response surface methodology. Concentrations of Tween 80 and Polyvinyl pyrrolidone (PVP K-30) were selected as independent variables that could optimize the formulation to obtain the desired entrapment efficacy and particle size/diameter. It was found that a formulation prepared using Tween 80 at a concentration of 2.55% and PVP K-30 at 2% could accomplish the goals for which an optimized formulation was needed. Either xanthan gum (XG) or thiolated xanthan gum (TXG) was added to the optimized formulation to determine how they affected the mucoadhesive properties of the formulation. Studies demonstrated that there was an initial burst release of ITH from the ITH/NC/XG and ITH/NC/TXG in the early hours and then a steady release for 24 h. As anticipated, the TXG formulation had a better mucin interaction, and this was needed to ensure that the drug was distributed to tissues that produce mucus. Finally, at the measured concentrations, the ITH/NC showed minimal cytotoxicity against lung cells, indicating that it may have potential for additional in vivo research. The enhanced bioavailability and mean residence time of the designed mucoadhesive NC formulations were confirmed by pharmacokinetic studies.

In Vitro and In Vivo Evaluation of Composite Oral Fast Disintegrating Film: An Innovative Strategy for the Codelivery of Ranitidine HCl and Flurbiprofen.

Here, we evaluate the feasibility of co-loading plain ranitidine hydrochloride (RHCl) and microencapsulated flurbiprofen (FBP) in a Lycoat® RS780-based oral fast disintegrating film (ODF). These films were developed by the solvent casting method to minimize the adverse effects of FBP and reduce the dosage form burden on patients. Optimized FBP microparticles (M3) with an average size of 21.2 ± 9.2 µm were loaded alone (F1) and in combination with plain RHCl (F2) in the composite ODF. All films were evaluated physicomechanically and physicochemically. These films were resilient, flexible, and disintegrated within thirty seconds. SEM images showed intact FBP microparticles in both formulations and, moreover, did not observe an interaction between the drug and film components. Microencapsulated FBP was released in a controlled manner over 48 h from the proposed formulations, while RHCl was released within 5 min from F2. After in vitro evaluation, formulations were also tested for in vivo anti-inflammatory activity, cytokine (TNF-α and IL-6) levels, and gastroprotective effects in rats. The anti-inflammatory activity and gastroprotective effect of F2 were markedly higher than pure FBP and other synthesized formulations (M3 and F1). The average score of gastric lesions was in the order of pure FBP (15.5 ± 1.32) > M3 (8 ± 2) > F1 (1 ± 0.5) > F2 (0.5 ± 0) > control (0). Additionally, F2 showed a sustained anti-inflammatory effect up to 10 h in the rat paw edema model. Furthermore, F2 also markedly reduced TNF-α and IL-6 levels. Conclusively, the Lycoat® RS780-based composite film could be a promising carrier for the co-loading of microencapsulated FBP with RHCl. In the future, an optimized formulation (F2) could be capable of countering the issues related to multiple drug administration in geriatric patients and evading the gastric irritation associated with FBP.

Fabrication, assessment, and optimization of alendronate sodium nanoemulsion-based injectable in-situ gel formulation for management of osteoporosis.

Low bone mass, degeneration of bone tissue, and disruption of bone microarchitecture are all symptoms of the disease osteoporosis, which can decrease bone strength and increase the risk of fractures. The main objective of the current study was to use a phospholipid-based phase separation in-situ gel (PPSG) in combination with an alendronate sodium nanoemulsion (ALS-NE) to help prevent bone resorption in rats. The effect of factors such as concentrations of the ALS aqueous solution, surfactant Plurol Oleique CC 497, and Maisine CC oil on nanoemulsion characteristics such as stability index and globular size was investigated using an l-optimal coordinate exchange statistical design. Injectable PPSG with the best nanoemulsion formulation was tested for viscosity, gel strength, water absorption, and in-vitro ALS release. ALS retention in the rats' muscles was measured after 30 days. The droplet size and stability index of the optimal nanoemulsion were 90 ± 2.0 nm and 85 ± 1.9%, respectively. When mixed with water, the optimal ALS-NE-loaded PPSG became viscous and achieved 36 seconds of gel strength, which was adequate for an injectable in-situ formulation. In comparison with the ALS solution-loaded in-situ gel, the newly created optimal ALS-NE-loaded PPSG produced the sustained and regulated release of ALS; hence, a higher percentage of ALS remained in rats' muscles after 30 days. PPSG that has been loaded with an ALS-NE may therefore be a more auspicious, productive, and effective platform for osteoporosis treatment than conventional oral forms.