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.

Journey into tomorrow: cardiovascular wellbeing transformed by nano-scale innovations.

Worldwide, cardiovascular diseases (CVDs) account for the vast majority of deaths and place enormous financial strains on healthcare systems. Gold nanoparticles, quantum dots, polymeric nanoparticles, carbon nanotubes, and lipids are innovative nanomaterials promising in tackling CVDs. In the setting of CVDs, these nanomaterials actively impact cellular responses due to their distinctive properties, including surface energy and topographies. Opportunities to more precisely target CVDs have arisen due to recent developments in nanomaterial science, which have introduced fresh approaches. An in-depth familiarity with the illness and its targeted mechanisms is necessary to use nanomaterials in CVDs effectively. We support the academic community's efforts to prioritize Nano-technological techniques in addressing risk factors linked with cardiovascular diseases, acknowledging the far-reaching effects of these conditions. The significant impact of nanotechnology on the early detection and treatment of cardiovascular diseases highlights the critical need for novel approaches to this pressing health problem, which is affecting people worldwide.

Biochemical and thermodynamic properties of de novo synthesized urease from Vicia sativa seeds with enhanced industrial applications.

Urease is one of the most significant enzymes in the industry. The objective of this research was to isolate and partially purify urease from Vicia sativa seeds with urease characterization. With a 6.4 % yield, the purification fold was 9.0. By using chromatography, it was determined that the isolated urease had a molecular weight of 55 kDa. The maximum urease activity was found following a 60-s incubation period at 40 °C and pH 8. The activity of urease was significantly boosted by a mean of calcium, barium, DL-dithiothreitol, Na2EDTA, and citrate (16.9, 26.6, 18.6, 13.6, and 31 %), respectively. But nickel and mercury caused inhibitory effects and completely inhibited urease activity, indicating the presence of a thiol (-SH) group in the enzyme active site. The Arrhenius plot was used to analyze the thermodynamic constants of activation, Ea, ΔH*, ΔG*, and ΔS*. The results showed that the values were 30 kJ/mol, 93.14 kJ/mol, 107.17 kJ/mol/K, and -40.80 J/mol/K, respectively. The significance of urease extraction from various sources may contribute to our understanding of the metabolism of urea in plants. The current report has novelty as it explained for the first time the kinetics and thermodynamics of hydrolysis of urea and inactivation of urease from V. sativa seeds.

Heartfelt living: Deciphering the link between lifestyle choices and cardiovascular vitality.

Cardiovascular diseases (CVDs) are still leading to a significant number of deaths worldwide despite the remarkable advancements in medical technology and pharmacology. Managing patients with established CVDs is a challenge for healthcare providers as it requires reducing the chances of recurring cardiovascular events. On the other hand, changing one's way of life can also significantly impact this area, reducing the likelihood of cardiovascular disease and death through their unique advantages. Consequently, it is advisable for healthcare providers to regularly advise their patients with coronary issues to participate in organized physical exercise and improve their overall physical activity. Additionally, patients should adhere to a diet that promotes heart health, cease smoking, avoid exposure to secondhand smoke, and address any psychosocial stressors that may heighten the risk of cardiovascular problems. These lifestyle therapies, whether used alongside drug therapy or on their own in patients who may have difficulty tolerating medications, face financial barriers, or experience ineffectiveness, can substantially reduce cardiovascular mortality and the likelihood of recurring cardiac events. Despite the considerable advancements in creating interventions, it is still necessary to determine the optimal intensity, duration, and delivery method for these interventions. Furthermore, it is crucial to carry out further investigations incorporating extended monitoring and assessment of clinical outcomes to get a more comprehensive comprehension of the efficacy of these therapies. Presenting the findings within the framework of "lifestyle medicine," this review seeks to offer a thorough synopsis of the most recent scientific investigations into the potential of behavioral modifications to lower cardiovascular disease risk.

Enhancement of antifungal activity and transdermal delivery of 5-flucytosine via tailored spanlastic nanovesicles: statistical optimization, in-vitro characterization, and in-vivo biodistribution study.

Aim and background: This current study aimed to load 5-flucytosine (5-FCY) into spanlastic nanovesicles (SPLNs) to make the drug more efficient as an antifungal and also to load the 5-FCY into a hydrogel that would allow for enhanced transdermal permeation and improved patient compliance. Methods: The preparation of 5-FCY-SPLNs was optimized by using a central composite design that considered Span 60 (X1) and the edge activator Tween 80 (X2) as process variables in achieving the desired particle size and entrapment efficiency. A formulation containing 295.79 mg of Span 60 and 120.00 mg of Tween 80 was found to meet the prerequisites of the desirability method. The optimized 5-FCY-SPLN formulation was further formulated into a spanlastics gel (SPG) so that the 5-FCY-SPLNs could be delivered topically and characterized in terms of various parameters. Results: As required, the SPG had the desired elasticity, which can be credited to the physical characteristics of SPLNs. An ex-vivo permeation study showed that the greatest amount of 5-FCY penetrated per unit area (Q) (mg/cm2) over time and the average flux (J) (mg/cm2/h) was at the end of 24 h. Drug release studies showed that the drug continued to be released until the end of 24 h and that the pattern was correlated with an ex-vivo permeation and distribution study. The biodistribution study showed that the 99mTc-labeled SFG that permeated the skin had a steadier release pattern, a longer duration of circulation with pulsatile behavior in the blood, and higher levels in the bloodstream than the oral 99mTc-SPNLs. Therefore, a 5-FCY transdermal hydrogel could possibly be a long-acting formula for maintenance treatment that could be given in smaller doses and less often than the oral formula.

Statistically Optimized Polymeric Buccal Films of Eletriptan Hydrobromide and Itopride Hydrochloride: An In Vivo Pharmacokinetic Study.

A migraine is a condition of severe headaches, causing a disturbance in the daily life of the patient. The current studies were designed to develop immediate-release polymeric buccal films of Eletriptan Hydrobromide (EHBR) and Itopride Hydrochloride (ITHC) to improve their bioavailability and, hence, improve compliance with the patients of migraines and its associated symptoms. The prepared films were evaluated for various in vitro parameters, including surface morphology, mechanical strength, disintegration test (DT), total dissolving time (TDT), drug release and drug permeation, etc., and in vivo pharmacokinetic parameters, such as area under curve (AUC), mean residence time (MRT), half-life (t1/2), time to reach maximum concentration (Tmax), and time to reach maximum concentration (Cmax). The outcomes have indicated the successful preparation of the films, as SEM has confirmed the smooth surface and uniform distribution of drugs throughout the polymer matrix. The films were found to be mechanically stable as indicated by folding endurance studies. Furthermore, the optimized formulations showed a DT of 13 ± 1 s and TDT of 42.6 ± 0.75 s, indicating prompt disintegration as well as the dissolution of the films. Albino rabbits were used for in vivo pharmacokinetics, and the outcomes were evident of improved pharmacokinetics. The drug was found to rapidly permeate across the buccal mucosa, leading to increased bioavailability of the drug: Cmax of 130 and 119 ng/mL of ITHC and EHBR, respectively, as compared to 96 (ITHC) and 90 ng/mL (EHBR) of oral solution. The conclusion can be drawn that possible reasons for the enhanced bioavailability could be the increased surface area in the form of buccal films, its rapid disintegration, and faster dissolution, which led toward the rapid absorption of the drug into the blood stream.

Preparation and In Vitro Evaluation of Levofloxacin-Loaded Floating Tables Using Various Rate-Controlling Agents.

Floating tablets are a new approach to extending the time a drug is in the stomach to improve therapy outcomes. Floating tablets were formulated with the drug, the polymers hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), and starch, fillers, and lubricants. The tablets were prepared using the direction compression method. The tablets' physical quality control tests were found to be within acceptable limits. The tablets extended drug release up to 12 h and were uniform in their drug contents. The swelling index of the tablets ranged from 60 ± 0.11 to 66 ± 0.14%, and the tablets were less dense than water. The floating lag time (10 ± 0.23 to 16 ± 0.09 s) and total floating time (>12 h) showed good floating behaviors. The kinetic modeling showed that the drug was released from the tablets by pseudo-diffusion, swelling, erosion, or anomalous non-Fickian diffusion. F6 (starch and CMC) showed higher n values (0.994 ± 0.04), exhibiting pseudo-zero-order drug release kinetics compared to those of other tablets. The dissolution data of the test and reference tables were not similar (P > 0.05). In terms of antimicrobial activity, the zones of inhibition of the test F6 tablet powders (5.3 ± 0.08 mm) and the reference tablet powders (5.9 ± 0.13 mm) were found to be significantly similar (P > 0.05). The study concluded that these floating tablets can improve the gastric residence time and therapeutic outcomes.

Formulation design and evaluation of epalrestat mouth dissolving tablets comprising superdisintegrant from natural sources manufactured by direct compression method and stability studies of optimized formulation.

Among the oral route, mouth dissolving tablets (MDTs) offer a benefit for drugs with slow dissolution and having low oral bioavailability. Epalrestat is one of the best effective diabetic neuropathy medication used for treating nerve pain. The problem associated with this drug is high first pass metabolism and low solubility in acidic media as well in basic media leads to short half-life, delayed dissolution and side effects. Therefore, the goal of the current work is to developed an epalrestat MDTs tablet that will provide quick drug dissolution and a quick onset of action for the treatment of nerve pain. MDTs of epalrestat were formulated by direct compression using natural superdis integrants obtained from the various sources such as fenugreek, gum karaya and banana powder. All of the pre- and post-compression parameter results were shown to be in accordance with established specifications. In comparison to other formulations of MDTs, formulation F3 with 15 mg (7.5%) of banana powder displayed a higher rate of dissolution. It was determined that epalrestat MDTs containing natural superdisintegrant were successfully formulated with acceptable physical and chemical properties, quick oral cavity disintegration, a quick onset of action and improved patient compliance.

Tobramycin-loaded nanoparticles of thiolated chitosan for ocular drug delivery: Preparation, mucoadhesion and pharmacokinetic evaluation.

The present work aimed to develop nanoparticles of tobramycin (TRM) using thiolated chitosan (TCS) in order to improve the mucoadhesion, antibacterial effect and pharmacokinetics. The nanoparticles were evaluated for their compatibility, thermal stability, particle size, zeta potential, mucoadhesion, drug release, kinetics of TRM release, corneal permeation, toxicity and ocular irritation. The thiolation of chitosan was confirmed by 1H NMR and FTIR, which showed peaks at 6.6 ppm and 1230 cm-1, respectively. The nanoparticles had a diameter of 73 nm, a negative zeta potential (-21 mV) and a polydispersity index of 0.15. The optimized formulation, NT8, exhibited the highest values of mucoadhesion (7.8 ± 0.541h), drug loading (87.45 ± 1.309%), entrapment efficiency (92.34 ± 2.671%), TRM release (>90%) and corneal permeation (85.56%). The release pattern of TRM from the developed formulations was fickian diffusion. TRM-loaded nanoparticles showed good antibacterial activity against Pseudomonas aeruginosa. The optimized formulation NT8 (0.1% TRM) greatly increased the AUC(0-∞) (1.5-fold) while significantly reducing the clearance (5-fold) compared to 0.3% TRM. Pharmacokinetic parameters indicated improved ocular retention and bioavailability of TRM loaded nanoparticles. Our study demonstrated that the TRM-loaded nanoparticles had improved mucoadhesion and pharmacokinetics and a suitable candidate for effective treatment of ocular bacterial 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.

Development and evaluation of pH sensitive semi-interpenetrating networks: assessing the impact of itaconic acid and aloe vera on network swelling and cetirizine release.

Hydrogels are crosslinked three-dimensional networks, and their properties can be easily tuned to target the various segments of the gastrointestinal tract (GIT). Cetirizine HCl (CTZ HCl) is an antihistaminic drug, which when given orally can upset the stomach. Moreover, this molecule has shown maximum absorption in the intestine. To address these issues, we developed a pH-responsive semi-interpenetrating polymer network (semi-IPN) for the delivery of CTZ HCl to the lower part of the GIT. Initially, 10 different formulations of itaconic acid-grafted-poly (acrylamide)/aloe vera [IA-g-poly (AAm)/aloe vera] semi-IPN were developed by varying the concentration of IA and aloe vera using the free radical polymerization technique. Based on swelling and sol-gel analysis, formulation F5 containing 0.3%w/w aloe vera and 6%w/w IA was chosen as the optimum formulation. The solid-state characterization of the optimized formulation (F5) revealed a successful incorporation of CTZ HCl in semi-IPN without any drug-destabilizing interaction. The in vitro drug release from F5 showed limited release in acidic media followed by a controlled release in the intestinal environment for over 72 h. Furthermore, during the in vivo evaluation, formulation F5 did not affect the hematological parameters, kidney, and liver functions. Clinical observations did not reveal any signs of illness in rabbits treated with hydrogels. Histopathological images of vital organs of treated animals showed normal cellular architecture. Thus, the results suggest a non-toxic nature and overall potential of the developed formulation as a targeted drug carrier.

Synthesis, Characterization, and Investigation of Novel Ionic Liquid-Based Tooth Bleaching Gels: A Step towards Safer and Cost-Effective Cosmetic Dentistry.

The objective of this study was to synthesize a novel choline hydroxide ionic liquid-based tooth bleaching gel. Ionic liquid-based gels were synthesized and characterized using FTIR along with pH testing. Tooth sample preparation was carried out in line with ISO 28399:2020. The effects of synthesized gels on tooth samples were tested. Tooth samples were stained and grouped into three experimental groups: EAI (22% choline hydroxide gel), EAII (44% choline hydroxide gel), and EB (choline citrate gel) and two control groups: CA (commercial at-home 16% carbamide peroxide gel) and CB (deionized water). The tooth color analysis, which included shade matching with the Vitapan shade guide (n = 2), and digital colorimetric analysis (n = 2) were evaluated. The surface characteristics and hardness were analyzed with 3D optical profilometry, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), and Microhardness testing (n = 3), respectively. The tooth color analysis (Vitapan shade guide) revealed that all the tooth samples treated with synthesized choline citrate gel (EB) showed an A1 shade as compared to the other four groups, giving a range of shades. An analysis of the ΔE values from digital colorimetry; EAI, EAII, CA, and CB showed ΔE values in a range that was clinically perceptible at a glance. However, EB showed the highest value of ΔE. The mean microhardness values for the five groups showed that the effects of three experimental gels i.e., 44% choline hydroxide, 22% choline hydroxide, and choline citrate, on the microhardness of the tooth samples were similar to that of the positive control, which comprised commercial at-home 16% carbamide peroxide gel. SEM with EDX of three tested subgroups was closely related in surface profile, elemental composition, and Ca/P ratio. The roughness average values from optical profilometry of four tested subgroups lie within approximately a similar range, showing a statistically insignificant difference (p > 0.05) between the tested subgroups. The synthesized novel experimental tooth bleaching gels displayed similar tooth bleaching actions without any deleterious effects on the surface characteristics and microhardness of the treated tooth samples when compared with the commercial at-home tooth bleaching gel.

Production, Characterization, and In Vitro and In Vivo Studies of Nanoemulsions Containing St. John's Wort Plant Constituents and Their Potential for the Treatment of Depression.

The current project was designed to prepare an oil-in-water (oil/water) hypericin nanoemulsion using eucalyptus oil for the preparation of an oil phase with chitosan as an emulsion stabilizer. The study might be a novelty in the field of pharmaceutical sciences, especially in the area of formulation development. Tween® 80 (Polysorbate) was used as the nonionic surfactant. The nanoemulsion was prepared by using the homogenization technique, followed by its physicochemical evaluation. The surface morphological studies showed the globular structure has a nano-sized diameter, as confirmed by zeta size analysis. The zeta potential analysis confirmed a positive surface charge that might be caused by the presence of chitosan in the formulation. The pH was in the range of 5.14 to 6.11, which could also be compatible with the range of nasal pH. The viscosity of the formulations was found to be affected by the concentration of chitosan (F1-11.61 to F4-49.28). The drug release studies showed that the presence of chitosan greatly influenced the drug release, as it was noticed that formulations having an elevated concentration of chitosan release lesser amounts of the drug. The persistent stress in the mouse model caused a variety of depressive- and anxiety-like behaviors that can be counteracted by chemicals isolated from plants, such as sulforaphane and tea polyphenols. In the behavioral test and source performance test, hypericin exhibited antidepressant-like effects. The results show that the mice treated for chronic mild stress had a considerably higher preference for sucrose after receiving continuous hypericin for 4 days (p = 0.0001) compared to the animals administered with normal saline (p ≤ 0.0001) as well as the naïve group (p ≤ 0.0001). In conclusion, prepared formulations were found to be stable and can be used as a potential candidate for the treatment of depression.

Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer.

M2 polarized tumor-associated macrophages (TAMs) have a multifunctional role in cancer initiation, progression, metastasis, and contribute to chemotherapeutic resistance. Therefore, identifying M2 polarized TAMs is a potential target for cancer therapeutic intervention. The underlying mechanism that target the TAMs M2 polarized macrophages remains primarily uncharacterized; however, only a few compounds have been identified that inhibit TAMs M2 polarized macrophages. In this research, we investigated that lapatinib could effectively suppress the expression of IL_13-induced M2 polarized macrophages surface markers i.e., CD163 and CD206, and downregulation of M2 genes such as Fizz1, Mrc1, Arg1, IL-10, Ym1, nd CCL2 in vitro. Moreover, lapatinib abrogated the M2 polarized macrophage-mediated cancer cells invasion and migration. Mechanistically, in our study, lapatinib inhibited IL-13 triggered STAT6 phosphorylation. Furthermore, in LLCs tumor model, lapatinib significantly reduced tumorigenesis, followed by the downregulation of percentages of M2 marker CD206+ and CD68+ in the tumor. This downregulation correlates with chemopreventive effect of lapatinib. All taken together, these results demonstrated that lapatinib effectively prevents the macrophage M2 polarization and indicates a potential mechanism for preventing the tumor growth via M2 polarized polarization intervention.

Plant-Derived Bioactive Compounds in the Management of Neurodegenerative Disorders: Challenges, Future Directions and Molecular Mechanisms Involved in Neuroprotection.

Neurodegenerative disorders encompass a wide range of pathological conditions caused by progressive damage to the neuronal cells and nervous-system connections, which primarily target neuronal dysfunction and result in problems with mobility, cognition, coordination, sensation, and strength. Molecular insights have revealed that stress-related biochemical alterations such as abnormal protein aggregation, extensive generation of reactive oxygen and nitrogen species, mitochondrial dysfunction, and neuroinflammation may lead to damage to neuronal cells. Currently, no neurodegenerative disease is curable, and the available standard therapies can only provide symptomatic treatment and delay the progression of the disease. Interestingly, plant-derived bioactive compounds have drawn considerable attention due to their well-established medicinal properties, including anti-apoptotic, antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as neuroprotective, hepatoprotective, cardioprotective, and other health benefits. Plant-derived bioactive compounds have received far more attention in recent decades than synthetic bioactive compounds in the treatment of many diseases, including neurodegeneration. By selecting suitable plant-derived bioactive compounds and/or plant formulations, we can fine tune the standard therapies because the therapeutic efficacy of the drugs is greatly enhanced by combinations. A plethora of in vitro and in vivo studies have demonstrated plant-derived bioactive compounds' immense potential, as proven by their capacity to influence the expression and activity of numerous proteins implicated in oxidative stress, neuroinflammation, apoptosis, and aggregation. Thus, this review mostly focuses on the antioxidant, anti-inflammatory, anti-aggregation, anti-cholinesterase, and anti-apoptotic properties of several plant formulations and plant-derived bioactive compounds and their molecular mechanisms against neurodegenerative disorders.

Formulation development of lipid polymer hybrid nanoparticles of doxorubicin and its in-vitro, in-vivo and computational evaluation.

The purpose of this study was to assess the parameters of doxorubicin (DOX) loaded lipid polymer hybrid nanoparticles (LPHNs) formulation development, and then the bioavailability of DOX were determined in the rabbit model, in order to evaluate the intrinsic outcome of dosage form improvement after the oral administration. LPHNs were prepared by combine approach, using both magnetic stirring and probe sonication followed by its characterization in terms of size-distribution (Zeta Size), entrapment efficiency (EE), loading capacity, and the kinetics of DOX. LPHNPs were further characterized by using scanning electron microscopy (SEM), powder X-Ray diffractometry (P-XRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), in vitro and in vivo studies. The molecular modeling was determined through the density functional theory (DFT) simulations and interactions. DOX loaded and unloaded LPHNs were administered orally to the rabbits for bioavailability and pharmacokinetic parameters determinations. The plasma concentration of DOX was determined through high performance liquid chromatography (HPLC). The average size of DOX-loaded LPHNs was 121.90 ± 3.0 nm. The drug loading of DOX was 0.391% ± 0.01 of aqueous dispersion, where its encapsulation efficiency was 95.5% ± 1.39. After oral administration of the DOX-LPHNs, the area under the plasma drug concentration-time curve (AUC) improved about 2-folds comparatively (p < 0.05). DFT simulations were used to understand the interactions of polymers with different sites of DOX molecule. The larger negative binding energies (-9.33 to -18.53 kcal/mol) of the different complexes evince that the polymers have stronger affinity to bind with the DOX molecule while the negative values shows that the process is spontaneous, and the synthesis of DOX-LPHNs is energetically favorable. It was concluded that DOX-LPHNs provides a promising new formulation that can enhance the oral bioavailability, which have optimized compatibilities and improve the pharmacokinetic of DOX after oral administration.

Tailoring and optimization of a honey-based nanoemulgel loaded with an itraconazole-thyme oil nanoemulsion for oral candidiasis.

The use of essential oil-based nanoemulsions (NEs) has been the subject of extensive research on a variety of conditions affecting the oral cavity. NEs are delivery methods that improve the solubility and distribution of lipid medicines to the intended areas. Because of their antibacterial and antifungal properties, itraconazole and thyme oil-based self-nanoemulsifying drug delivery systems (ItZ-ThO-SNEDDS) were created to protect oral health against oral microorganisms. The ItZ-ThO-SNEDDS were created utilizing an extreme verices mixture design, and varying concentrations of ThO (10% and 25%), labrasol (40% and 70%), and transcutol (20% and 40%) were used. The ItZ-ThO-SNEDDS had droplet sizes of less than 250 nm, a drug-loading efficiency of up to 64%, and a fungal growth inhibition zone of up to 20 mm. The accepted design was used to obtain the ideal formulation, which contained ThO in the amount of 0.18 g/ml, labrasol 0.62 g/ml, and transcutol 0.2 g/ml. The best ItZ-ThO-SNEDDS formulation was incorporated into a honey-based gel, which demonstrated improved release of ItZ in vitro and improved transbuccal permeation ex vivo. In addition, when compared with various formulations tested in rats, the optimized loaded emulgel decreased the ulcer index. This study therefore demonstrated that the ItZ-ThO-SNEDDS could offer an effective defense against oral diseases caused by microbial infections.

Polycaprolactone based pharmaceutical nanoemulsion loaded with acriflavine: optimization and in vivo burn wound healing activity.

Cutaneous burn wounds are a common and troublesome critical issue of public health. Over the last decade, many researchers have investigated the development of novel therapeutic modalities which are capable of fully regeneration and reinstatement of structure and function of the skin with no or limited scar formation. Novel pharmaceutical carriers are offering a potential platform to deliver the drug effectively and to overcome the limitation associated with conventional wound dressings. The aim of this study was to investigate a pharmaceutical acriflavine-loaded polycaprolactone nanoemulsion (ACR-PCL-NE) for burn wound healing. Nanoemulsion was prepared by using the double emulsion solvent evaporation technique and it was subjected to thermodynamic stability testing, droplet size, polydispersity, zeta potential, pH, and surface morphology analysis. The in vivo study was performed to evaluate the efficacy of nanoemulsion using Sprague-Dawley rats as an animal model. The results of this study revealed that the optimized nanoemulsion was stable and had desirable physicochemical properties. The pH was about 4.02 at 25 °C and the particle size was found to be in the range of 302 ± 4.62 nm while the zeta potential was -7.8 ± 1.22 mV and the polydispersity index of 0.221 ± 0.017. The wound regeneration process was evaluated in vivo by different techniques, the formulation group (FG) showed high wound healing potential as compared to the standard group (SD) and control group (CG). These findings reveal that this nanoemulsion formulation can be used effectively for wound healing.

Biodegradable Polymers-Based Smart Nanocrystals for Loxoprofen Delivery with Enhanced Solubility: Design, Fabrication and Physical Characterizations.

Nanocrystals are carrier-free, submicron-sized, colloidal drug delivery systems with particle sizes in the mean nanometer range. Nanocrystals have high bioavailability and fast absorption because of their high dissolution velocity and enhanced adhesiveness to cell membranes. Loxoprofen, a nonsteroidal anti-inflammatory drug belonging to the Biopharmaceutical Classification System (BCS) II drug class, was selected as the model drug. The aim of this study was to formulate nanocrystals of loxoprofen. A total of 12 formulations (F1 to F12) were prepared. An antisolvent technique was used to determine the effects of various stabilizers and processing conditions on the optimization of formulations. The various stabilizers used were hydroxypropyl methylcellulose (0.5%), polyvinylpyrrolidone (0.5%), and sodium lauryl sulfate (0.1%). The various characterizations conducted for this research included stability studies at 25 °C and 4 °C, scanning electron microscopy, transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), zeta potentials, polydispersity indexes, and dissolution studies. F10 was the optimized formulation that showed stability at room temperature, as well as at a refrigerated temperature, for 30 days. A high dissolution rate (100% within the first 10 min) was shown by comparative dissolution studies of nano-suspensions with the micro-suspension and raw loxoprofen. F10 formulation had a non-porous and crystalline morphology on evaluation by TEM and XRPD, respectively, and the average particle size was 300 ± 0.3 nm as confirmed by TEM. DSC recorded a reduction in the melting point (180 °C processed and 200 °C unprocessed melting points). The dissolution rate and solubility of the formulated loxoprofen nanocrystals were significantly enhanced. It can be concluded that selecting suitable stabilizers (i.e., polymers and surfactants) can produce stable nanocrystals, and this can potentially lead to a scaling up of the process for commercialization.