Enhancing the Topical Antibacterial Activity of Fusidic Acid via Embedding into Cinnamon Oil Nano-Lipid Carrier.

Presently, antimicrobial resistance is of great risk to remarkable improvements in health conditions and infection management. Resistance to various antibiotics has been considered a great obstacle in their usage, necessitating alternative strategies for enhancing the antibacterial effect. Combination therapy has been recognized as a considerable strategy that could improve the therapeutic influence of antibacterial agents. Therefore, the aim of this study was to combine the antibacterial action of compounds of natural origin like fusidic acid (FA) and cinnamon essential oil (CEO) for synergistic effects. A distinctive nanoemulsion (NE) was developed using cinnamon oil loaded with FA. Applying the Box-Behnken design (BBD) approach, one optimized formula was selected and integrated into a gel base to provide an FA-NE-hydrogel for optimal topical application. The FA-NE-hydrogel was examined physically, studied for in vitro release, and investigated for stability upon storage at different conditions, at room (25 °C) and refrigerator (4 °C) temperatures, for up to 3 months. Ultimately, the NE-hydrogel preparation was inspected for its antibacterial behavior using multidrug-resistant bacteria and checked by scanning electron microscopy. The FA-NE-hydrogel formulation demonstrated a pH (6.32), viscosity (12,680 cP), and spreadability (56.7 mm) that are acceptable for topical application. The in vitro release could be extended for 6 h, providing 52.0%. The formulation was stable under both test conditions for up to 3 months of storage. Finally, the FA-NE-hydrogel was found to inhibit the bacterial growth of not only Gram-positive but also Gram-negative bacteria. The inhibition was further elucidated by a scanning electron micrograph, indicating the efficiency of CEO in enhancing the antibacterial influence of FA when combined in an NE system.

Date Palm Extract (Phoenix dactylifera) Encapsulated into Palm Oil Nanolipid Carrier for Prospective Antibacterial Influence.

It is worthwhile to note that using natural products today has shown to be an effective strategy for attaining the therapeutic goal with the highest impact and the fewest drawbacks. In Saudi Arabia, date palm (Phoenix dactylifera) is considered the principal fruit owing to its abundance and incredible nutritional benefits in fighting various diseases. The main objective of the study is to exploit the natural products as well as the nanotechnology approach to obtain great benefits in managing disorders. The present investigation focused on using the powder form of date palm extract (DPE) of Khalas cultivar and incorporates it into a nanolipid formulation such as a nanostructured lipid carrier (NLC) prepared with palm oil. Using the quality by design (QbD) methodology, the most optimized formula was chosen based on the number of assigned parameters. For more appropriate topical application, the optimized DP-NLC was combined with a pre-formulated hydrogel base forming the DP-NLC-hydrogel. The developed DP-NLC-hydrogel was evaluated for various physical properties including pH, viscosity, spreadability, and extrudability. Additionally, the in vitro release of the formulation as well as its stability upon storage under two different conditions of room temperature and refrigerator were investigated. Eventually, different bacterial strains were utilized to test the antibacterial efficacy of the developed formulation. The optimized DP-NLC showed proper particle size (266.9 nm) and in vitro release 77.9%. The prepared DP-NLC-hydrogel showed acceptable physical properties for topical formulation, mainly, pH 6.05, viscosity 9410 cP, spreadability 57.6 mm, extrudability 84.5 (g/cm2), and in vitro release 42.4%. Following three months storage under two distinct conditions, the formula exhibited good stability. Finally, the antibacterial activity of the developed DP-NLC-hydrogel was evaluated and proved to be efficient against various bacterial strains.

Tea Tree Oil Nanoemulsion-Based Hydrogel Vehicle for Enhancing Topical Delivery of Neomycin.

The present investigation aims to improve the antimicrobial influence of certain antibacterial drugs, namely, neomycin (NEO), exploiting the benefits of natural oils such as tea tree oil (TTO). Therefore, a distinctive nanolipid formulation, namely, a nanoemulsion (NE), was developed using a Central Composite Factorial Design (CCD) approach depending on the amount of TTO and tween 80 as surfactant. The optimized NEO-NE formula exhibiting minimum globular size and maximum in vitro release was selected. For efficient topical delivery, NEO-NE was incorporated into a pre-formulated hydrogel. The developed NEO-NE-hydrogel was characterized by its physical characteristics such as pH, viscosity, and spreadability. Next, it was tested for stability under different conditions for 3 months. Ultimately, an irritation test was conducted followed by an antibacterial examination. The preparation demonstrated acceptable properties to be successfully applied topically. It showed non-significant changes in stability in both conditions up to 3 months storage when compared to a fresh preparation. It exhibited no irritation when applied on hairless animal skin. Finally, TTO revealed a good inhibition for the bacterial growth that could improve the influence of NEO antibacterial activity, indicating the efficiency of NE containing NEO prepared with TTO to be a promising antibacterial nanocarrier.

Development and Optimization of Nigella sativa Nanoemulsion Loaded with Pioglitazone for Hypoglycemic Effect.

Diabetes mellitus (DM) is a metabolic disorder associated with an increased blood glucose level. The world health burden of DM has increased as a result of numerous causes that necessitates suitable treatment. Pioglitazone (PGZ) is a generally prescribed medication for managing type II diabetes. However, its low solubility creates complications for its formulation. Therefore, the aim of the current study was to incorporate PGZ into a nanoemulsion (NE) formulation prepared with Nigella sativa oil (NSO) to boost the action of PGZ. To our knowledge, no previous study has addressed the combination and synergistic effect of PGZ and NSO as a hypoglycemic NE formulation intended for oral administration. An experiment was designed to test several PGZ-loaded NE formulations, varying factors such as NSO, surfactant and co-surfactant concentrations. These factors were investigated for their influence on responses including particle size and in vitro release. An optimized PGZ-loaded NE was selected and examined for its morphology, kinetic activity and stability. Further, the anti-diabetic effect of the optimized formulation was evaluated using diabetically induced rats. The optimized formula exhibited a good particle size of 167.1 nm and in vitro release of 89.5%. A kinetic study revealed that the drug release followed the Korsmeyer-Peppas mechanism. Additionally, the PGZ-loaded NE formulation was found to be stable, showing non-significant variation in the evaluated parameters when stored at 4 and 25 °C for a period of 3 months. In vivo investigation of the PGZ-loaded NE formulation showed a significant reduction in blood glucose level, which appeared to be enhanced by the presence of NSO. In conclusion, NS-NE could be a promising nanocarrier for enhancing the hypoglycemic effect of PGZ.

Hypolipidemic Activity of Olive Oil-Based Nanostructured Lipid Carrier Containing Atorvastatin.

Currently, hyperlipidemia is a growing health issue that is considered a risk factor for obesity. Controlling body weight and modifying life style in most of cases are not adequate and the condition requires medical treatment. Statin drugs (mainly Atorvastatin (ATO)), have been used broadly and for long time as medications for handling higher levels of lipid, especially bad cholesterol, which accordingly controls the prevalence of obesity. Still, the obstacle that stands in front of any formulation is the poor solubility of the drug. Low solubility of ATO came up with poor absorption as well as poor bioavailability. This paved the way for the present study, which aimed to exploit nanotechnology and develop certain nanolipid carriers that could accommodate hydrophobic drugs, such as ATO. Nanostructured lipid carrier (NLC) containing ATO was fabricated using olive oil. Olive oil is natural plant oil possessing confirmed hypolipidemic activity that would help in improving the efficacy of the formulation. Via applying the Quality by Design (QbD) approach, one NLC formula was selected to be optimized based on appropriate size and higher entrapment. Optimized ATO-NLC was scrutinized for zeta potential, in vitro study and kinetic profile. Moreover, stability testing and in vivo hypolipidemic behavior was conducted. The optimized NLC formulation seemed to show particle size (254.23 nm) with neutral zeta potential (-1.77 mV) and entrapment efficiency (69.56%). The formulation could be prolonged for 12 h and provided higher % of release (97.17%). Stability testing confirmed the role of modifying the surface of the formulation with PEG-DSPE in providing a highly stable formulation that could withstand three months storage in two altered conditions. Ultimately, optimized ATO-NLC could successfully lower total cholesterol level in rats induced with obesity and fed a high-fat diet. Remarkably, ATO-NLC prepared with olive oil, in addition to shielding its surface, would provide a stable formulation that holds up the synergistic action between olive oil and ATO.

Shea Butter Potentiates the Anti-Bacterial Activity of Fusidic Acid Incorporated into Solid Lipid Nanoparticle.

Fusidic acid (FA) is an efficient anti-bacterial drug proven to be efficient against a wide range of bacteria. Nevertheless, the main restriction in its formulation is the limited solubility. To avoid such an obstacle, the drug is incorporated into the lipid core of the nanolipid formulation. Consequently, the present study was an attempt to formulate nanolipid preparation, mainly, solid lipid nanoparticle (SLN) integrating FA. FA-SLN was prepared using shea butter as a lipid phase owing to its reported anti-bacterial activity. Different FA-SLNs were fabricated using the central composite design (CCD) approach. The optimized formula was selected and integrated into a hydrogel base to be efficiently used topically. FA-SLN-hydrogel was evaluated for its character, morphology, in vitro release and stability. The formula was examined for irritation reaction and finally evaluated for its anti-bacterial performance. The optimized formula showed particle size 283.83 nm and entrapment 73.057%. The formulated FA-SLN-hydrogel displayed pH 6.2, viscosity 15,610 cP, spreadability 51.1 mm and in vitro release 64.6% following 180 min. FA-SLN-hydrogel showed good stability for three months at different conditions (room temperature and refrigerator). It exhibited no irritation reaction on the treated rats. Eventually, shea butter displayed a noteworthy effect against bacterial growth that improved the effect of FA. This would indicate prospective anti-bacterial activity of FA when combined with shea butter in SLN formulation as a promising nanocarrier.

Development, Characterization and Optimization of the Anti-Inflammatory Influence of Meloxicam Loaded into a Eucalyptus Oil-Based Nanoemulgel.

The purpose of the present study was to explore the influence of a certain natural essential oil, namely eucalyptus oil, as an anti-inflammatory agent in addition to its prospective role in enhancing the action of meloxicam in reducing inflammation. As far as we know, this has been the first integration of meloxicam and eucalyptus essential oil into a nanoemulgel formulation intended for topical use. Primarily, eucalyptus oil was utilized in developing a nanoemulsion formulation incorporating meloxicam. A 22 factorial design was constructed using two independent variables (oil concentration and surfactant concentration) with two responses (particle size and % of in vitro release). One optimized formula was selected depending on the desirability function and subjected to a stability study. The optimized nanoemulsion was mixed with HPMC as a gelling agent to produce a meloxicam-loaded nanoemulgel, which was examined for its properties, stability, in vitro release and ex vivo permeation. Eventually, the anti-inflammatory activity was evaluated and compared with a placebo and corresponding gel formulation. The developed nanoemulgel revealed acceptable physical characteristics to be applied topically. Studying of the in vitro release was conducted successfully for 6 h. The ex vivo permeation from the nanoemulgel formulations was prompted, showing an appropriate value of the steady-state transdermal flux (SSTF). As a final point, the anti-inflammatory activity of the developed nanoemulgel revealed a valued anti-inflammatory influence. Additionally, the concurrence of eucalyptus essential oil and meloxicam was assured, and their potential in combating and lowering inflammation was supported.

Novel Formulation of Fusidic Acid Incorporated into a Myrrh-Oil-Based Nanoemulgel for the Enhancement of Skin Bacterial Infection Treatment.

Fusidic acid (FA) is renowned as an effective bacteriostatic agent obtained from the fungus Fusidium coccineum, used for treating various eye and skin disorders. The objective of the present study was to develop, characterize, and evaluate the antibacterial activity of a novel FA nanoemulgel for topical skin application. Primarily, various fusidic acid nanoemulsion formulations were fabricated using different concentrations of myrrh essential oil, Tween 80 as a surfactant, and Transcutol® P as a co-surfactant. A Box−Behnken design was employed to select the optimized FA nanoemulsion formulation, based on the evaluated particle size and % of in vitro release as dependent variables. The optimized formula was incorporated within a hydrogel to obtain an FA nanoemulgel (FA-NEG) preparation. The formulated FA-NEG was evaluated for its visual appearance, pH, viscosity, and spreadability, compared to its corresponding prepared fusidic acid gel. In vitro release, kinetic study, and ex vivo drug permeation were implemented, followed by formulation stability testing. The FA-NEG exhibited a smooth and homogeneous appearance, pH value (6.61), viscosity (25,265 cP), and spreadability (33.6 mm), which were all good characteristics for appropriate topical application. A total of 59.3% of FA was released from the FA-NEG after 3 h. The ex vivo skin permeability of the FA-NEG was significantly enhanced by 3.10 ± 0.13-fold, showing SSTF of 111.2 ± 4.5 µg/cm2·h when compared to other formulations under investigation (p < 0.05). No irritation was observed upon applying the FA-NEG to animal skin. Eventually, it was revealed that the FA-NEG displayed improved antibacterial activity against a wide variety of bacteria when compared to its corresponding FA gel and marketed cream, indicating the prospective antibacterial effect of myrrh essential oil. In conclusion, the recommended formulation offers a promising antibacterial approach for skin infections.

Geraniol Averts Methotrexate-Induced Acute Kidney Injury via Keap1/Nrf2/HO-1 and MAPK/NF-κB Pathways.

OBJECTIVES: Geraniol, a natural monoterpene, is an essential oil component of many plants. Methotrexate is an anti-metabolite drug, used for cancer and autoimmune conditions; however, clinical uses of methotrexate are limited by its concomitant renal injury. This study investigated the efficacy of geraniol to prevent methotrexate-induced acute kidney injury and via scrutinizing the Keap1/Nrf2/HO-1, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 and -9 pathways. METHODS: Male Wister rats were allocated into five groups: control, geraniol (orally), methotrexate (IP), methotrexate and geraniol (100 and 200 mg/kg). RESULTS: Geraniol effectively reduced the serum levels of creatinine, urea and Kim-1 with an increase in the serum level of albumin when compared to the methotrexate-treated group. Geraniol reduced Keap1, escalated Nrf2 and HO-1, enhanced the antioxidant parameters GSH, SOD, CAT and GSHPx and reduced MDA and NO. Geraniol decreased renal P38 MAPK and NF-κB and ameliorated the inflammatory mediators TNF-α, IL-1ß, IL-6 and IL-10. Geraniol negatively regulated the apoptotic mediators Bax and caspase-3 and -9 and increased Bcl2. All the biochemical findings were supported by the alleviation of histopathological changes in kidney tissues. CONCLUSION: The current findings support that co-administration of geraniol with methotrexate may attenuate methotrexate-induced acute kidney injury.

Geraniol isolated from lemon grass to mitigate doxorubicin-induced cardiotoxicity through Nrf2 and NF-κB signaling.

BACKGROUND: Geraniol, a natural monoterpene, is a component of many plant essential oils. It contains many medicinal and pharmacological properties. Doxorubicin is an anticancer drug; however, its clinical usage is limited due to its cumulative and dose-dependent cardiotoxicity. This study investigates geraniol as a protective agent against doxorubicin-induced cardiotoxicity and explores possible underlying mechanisms of action. METHODS: Male Sprague-Dawley rats were allocated into five groups. Groups 1 and 2 were administered saline and geraniol 200 mg/kg/day/orally, respectively, for 15 days. Group 3 was administered intraperitoneal doxorubicin (5 mg/kg/IP on the 5th, 10th and 15th days to achieve a cumulative dose of 15 mg/kg) to induce cardiotoxicity. The fourth and fifth groups were treated with either geraniol 100 mg/kg or 200 mg/kg orally and doxorubicin to equal the doxorubicin dose administered to Group 3. RESULTS: Treatment with geraniol significantly ameliorated cardiac damage and restored serum cardiac injury marker levels in doxorubicin treated animals. Geraniol upregulated Nrf2 and HO-1 expression, elevated total antioxidant capacity, decreased the nuclear accumulation of kappa-light-chain enhancer of activated B cells (NF-κB), decreased the phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), suppressed tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin-18 (IL-18) levels, and restored the levels of Bax and caspase-3 and 9 in heart tissue. CONCLUSION: Geraniol may function as a potential activator of nuclear factor erythroid 2-related factor 2 (Nrf2), which subsequently improves Nrf2-dependent antioxidative signaling, diminishes apoptosis and subdues the inflammatory response. The downstream result is protection of the heart from doxorubicin-induced cardiotoxicity.

Quality by Design for Development, Optimization and Characterization of Brucine Ethosomal Gel for Skin Cancer Delivery.

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (32) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.

Curcumin Niosomes Prepared from Proniosomal Gels: In Vitro Skin Permeability, Kinetic and In Vivo Studies.

Curcumin is a poorly water-soluble drug that is used for the treatment of inflammations, tumors, wound healing antioxidant and other diseases. In the current manuscript, it is successfully formulated into proniosome gels. The proniosomes are readily hydrated into niosomal formulations using warm water. Proniosomes were prepared using nonionic surfactants (tween 80, span 60) either solely or in combinations with cholesterol. The produced niosomal formulations were homogenous in size with vesicular sizes >343 and <1800 nm. The encapsulation efficiency percentage "EE%" of curcumin in niosomal formulations was different according to niosomal composition. It increased up to 99.74% in formulations of tween 80/Chol of 200 µmole/mL lipid concentration. Span 60/chol niosomes showed decreased curcumin EE%. Niosomal formulations showed increased SSTF and PC with enhancement ratios of more than 20-fold compared with curcumin suspension form. Kinetically, niosomes fitted to the Korsemeyer-Peppas model with non-Fickian transport according to their calculated n-values where curcumin suspension form showed Korsemeyer-Peppas kinetics with Fickian transport. Niosomal formulations deposited higher curcumin amounts in the skin compared with the suspension form. The best niosomal formulation (F9) was used for niosomal gel and emulgel fabrication. Finally, the anti-inflammatory activity of curcumin in various formulations was evaluated using a rat hind paw edema method and the % of swelling was 17.5% following 24 h in group treated with curcumin niosomal emulgel. In conclusion, this study suggests that the developed niosomal emulgel could significantly enhance the anti-inflammatory effect of curcumin and be an efficient carrier for the transdermal delivery of the drug.

Date Palm Extract (Phoenix dactylifera) PEGylated Nanoemulsion: Development, Optimization and Cytotoxicity Evaluation.

Date palm fruit (Phoenix dactylifera) is reputed to have numerous biological activities, including anticancer properties. To utilize the great fortune of this fruit, the current study aimed to maximize its pharmacological activity. Date palm extract (DPE) of Khalas cultivar was obtained in powder form and then was formulated into nanoemulsion (NE). The optimized DPE-NE was formulated along with its naked counterpart followed by studying their physical and chemical properties. A qualitative assessment of total serum protein associated with the surface of formulations was implemented. Studies for the in vitro release of DPE from developed NE before and after incubation with serum were investigated. Eventually, an MTT assay was conducted. Total phenolic and flavonoid contents were 22.89 ± 0.013 mg GAE/g of dry DPE and 9.90 ± 0.03 mg QE/g of dry DPE, respectively. Homogenous NE formulations were attained with appropriate particle size and viscosity that could be administered intravenously. The optimized PEGylated NE exhibited a proper particle size, PDI, and zeta potential. Total serum protein adsorbed on PEG-NE surface was significantly low. The release of the drug through in vitro study was effectively extended for 24 h. Ultimately; PEGylated NE of DPE attained significant inhibition for cancer cell viability with IC50 values of 18.6 ± 2.4 and 13.5 ± 1.8 µg/mL for MCF-7 and HepG2 cell lines, respectively. PEGylated NE of DPE of Khalas cultivar will open the gate for future adjuvants for cancer therapy.

Enhancement of Curcumin Anti-Inflammatory Effect via Formulation into Myrrh Oil-Based Nanoemulgel.

BACKGROUND: Curcumin (Cur) possesses a variety of beneficial pharmacological properties including antioxidant, antimicrobial, anti-cancer and anti-inflammatory activities. Nevertheless, the low aqueous solubility and subsequent poor bioavailability greatly limits its effectiveness. Besides, the role of myrrh oil as an essential oil in treating inflammatory disorders has been recently demonstrated. The objective of the current investigation is to enhance Cur efficacy via developing Cur nanoemulgel, which helps to improve its solubility and permeability, for transdermal delivery. METHODS: The formulated preparations (Cur gel, emulgel and nanoemulgel) were evaluated for their physical appearance, spreadability, viscosity, particle size, in vitro release and ex vivo drug permeation studies. The in vivo anti-inflammatory activity was estimated using the carrageenan-induced rat hind paw edema method. RESULTS: The formulated Cur-loaded preparations exhibited good physical characteristics that were in the acceptable range of transdermal preparations. The release of Cur from gel, emulgel and nanoemulgel after 12 h was 72.17 ± 3.76, 51.93 ± 3.81 and 62.0 ± 3.9%, respectively. Skin permeation of Cur was significantly (p < 0.05) improved when formulated into nanoemulgel since it showed the best steady state transdermal flux (SSTF) value (108.6 ± 3.8 µg/cm2·h) with the highest enhancement ratio (ER) (7.1 ± 0.2). In vivo anti-inflammatory studies proved that Cur-loaded nanoemulgel displayed the lowest percent of swelling (26.6% after 12 h). CONCLUSIONS: The obtained data confirmed the potential of the nanoemulgel dosage form and established the synergism of myrrh oil and Cur as an advanced anti-inflammatory drug.

Enhancement of Anti-Inflammatory Activity of Optimized Niosomal Colchicine Loaded into Jojoba Oil-Based Emulgel Using Response Surface Methodology.

Recent progression in investigational studies aiming to integrate natural products and plant oils in developing new dosage forms that would provide optimal therapeutic effect. Therefore, the aim of the present exploration was to inspect the influence of jojoba oil in boosting the anti-inflammatory effect of colchicine natural product. To our knowledge, there is no formulation comprising colchicine and jojoba oil together to form a niosomal emulgel preparation anticipated for topical application. Colchicine is a natural product extracted from Colchicum autumnale that has been evidenced to show respectable anti-inflammatory activity. Owing to its drawbacks and low therapeutic index, it was preferable to be formulated into topical dosage form. The current study inspected colchicine transdermal delivery by developing niosomal preparation as a potential nanocarrier included into emulgel prepared with jojoba oil. Box Behnken design was constructed to develop 17 niosomal emulgel formulations. The optimized colchicine niosomal emulgel was evaluated for its physical characteristics and in vitro release studies. The in vivo anti-inflammatory activity was estimated via carrageenan-induced rat hind paw edema method. The developed colchicine niosomal preparation revealed particle size of 220.7 nm with PDI value 0.22, entrapment efficiency 65.3%. The formulation was found to be stable showing no significant difference in particle size and entrapment efficiency up on storage at 4 °C and 25 °C for 3 months. The optimized colchicine niosomal emulgel exhibited a pH value 6.73, viscosity 4598 cP, and spreadability 38.3 mm. In vitro release study of colchicine from niosomal emulgel formulation was around 52.4% over 6 h. Apparently, the proficient anti-inflammatory activity of colchicine niosomal emulgel was confirmed via carrageenan-induced rat hind paw edema test. Overall, the results recommend the combination of niosomal preparation with jojoba oil-based emulgel that might signify a favorable delivery of anti-inflammatory drug such as colchicine.

Enhancement in antinociceptive and anti-inflammatory effects of tramadol by transdermal proniosome gel.

Oral therapy of tramadol, an opiate analgesic, undergoes extensive hepatic metabolism and requires frequent administration. Transdermal therapy by virtue can overcome these issues and can improve the efficacy and reduce abuse liability of tramadol. The aim of this research was to investigate the possibility of transdermal delivery of tramadol by formulating proniosome gel and evaluate its therapeutic potential in vivo. The effect of formulation composition as well as amount of drug on physicochemical characteristics of prepared proniosomes were examined. Best proniosome gel (F4) was selected and evaluated for drug release, stability and transdermal efficacy by ex vivo and in vivo experiments. The vesicles demonstrated optimal properties including spherical shape, nanosize with good entrapment efficiency, adequate zeta potential, higher stability and greater transdermal flux. The amorphization and dispersion of tramadol in the aqueous core of proniosome vesicles was confirmed by differential scanning calorimeter. Release profile of F4 was distinct (P < 0.001) from control and displayed steady and prolonged tramadol release by Fickian diffusion. Transdermal therapy of F4 showed prominent reduction of induced twitches (P < 0.005) in mice and edema (P < 0.05) in rats, as compared to oral tramadol. The improvement in clinical efficacy of tramadol in transdermal therapy is correlated with the pharmacokinetic data observed. In conclusion, the observed improvement in antinociceptive and anti-inflammatory effects from proniosome carriers signifies its potential to be a suitable alternative to oral therapy of tramadol with greater efficacy.

Therapeutic Applications of Biostable Silver Nanoparticles Synthesized Using Peel Extract of Benincasa hispida: Antibacterial and Anticancer Activities.

The purpose of this study was to fabricate biostable inorganic silver nanoparticles (AgNPs) using fresh peel (aqueous) extract of Benincasa hispida. A fast, robust, and eco-friendly approach was used for the synthesis of AgNPs, where bioactive components of peel extract of B. hispida acted as reducing and stabilizing agents. Synthesized AgNPs were characterized using a UV-Vis spectrophotometer, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and electron microscopy. The synthesized nanoparticles exhibited maximum absorption at 418 nm under the typical AgNPs surface plasmon resonance band range. They depicted a mean size of 26 ± 2 nm with a spherical shape. Their therapeutic prospective was determined by evaluating their antimicrobial and anticancer potential. The bio-synthesized silver nanoparticles exhibited strong antimicrobial activity with minimum inhibitory concentration (MIC 50) values of 14.5, 8.6, 6.063, and 13.4 µg/mL against Staphylococcus aureus (ATCC 25923), Micrococcus luteus (ATCC 14593), Escherichia coli (ATCC 25922), and Klebsiella pneumonia (ATCC 13883), respectively. The biosynthesized AgNPs showed potent in vitro cytotoxicity against human cervical cancer cell line with a half maximal inhibitory concentration (IC50) value of 0.066 µg/mL; however, no cytotoxic effect was observed on normal human primary osteoblasts cell line. This study explored B. hispida extract and confirmed its effectiveness as a promising source in producing AgNPs that could be employed for several therapeutic applications.

Mucoadhesive buccal film of almotriptan improved therapeutic delivery in rabbit model.

Administration of almotriptan as an oral therapy is largely limited because of poor aqueous solubility and rather low bioavailability. The aim of present investigation was to formulate oral mucoadhesive film of almotriptan to improve the drug delivery and desired therapeutic effects. Placebo films (F1-F8) were prepared by varying the concentrations of Proloc 15 (7.5-15% w/v) and Eudragit RL 100/RS 100 (15-30% w/v) polymers. Physicomechanical and pharmaceutical characteristics of drug loaded films (FA1-FA4) were examined. Selected FA4 film was evaluated in vivo by assessing the pharmacokinetic profile and compared with oral therapy in rabbits. FA1-FA4 films exhibited excellent physicomechanical properties and rapid hydration. A biphasic and considerably greater drug release (p < 0.05) was observed in FA3 and FA4 films contain higher amount of hydrophilic polymer. The rate of permeation of almotriptan was found to be significantly higher in FA4 than FA3 film (p < 0.005). Fourier transform infrared spectral scan indicates no incompatibility exists between the drug and polymers used. Differential scanning calorimetry thermogram represents the evidence of almotriptan amorphization and molecular dispersion of it in the film. Scanning electron microscopy images shows that FA4 possess good morphological features and hence suitable for use in the buccal application. In vivo data demonstrated rapid and efficient absorption (p < 0.005) of almotriptan with greater AUC0-12 (>2 folds, p < 0.0001) by FA4 film as compared to oral (control). In general, the data established the potential of FA4 film to improve the therapeutic delivery of almotriptan and offers a promising option in migraine therapy.

Dual-targeting potential of active constituents of Nigella sativa against FimH and CTX-M-15: A plausible therapeutic strategy against drug-resistant uropathogenic strains.

Uropathogenic strains belonging to the Enterobacteriaceae family are considered one of factors for urinary tract infections, and type 1 pilus fimbrial adhesin (FimH) and beta lactamase CTX-M-15 play crucial roles in their pathogenesis and resistance. Thus, a promising approach is to explore dual-targeting therapeutic agents that act against both FimH and CTX-M-15. In the present study, active constituents of Nigella sativa were selected on the basis of significant activity against UTIs. Molecular docking was used to target active constituents of Nigella sativa to the active sites of FimH and CTX-M-15; these included thymoquinone, dithymoquinone, carvacrol, p-cymene, thymol, thymohydroquinone and longifolene. Dithymoquinone was found to be the most potent dual inhibitor, with binding energy of -7.01 and -5.38kcal/mol against CTX-M-15 and FimH, respectively; In addition, Dithymoquinone exhibited superior activity compared to positive controls avibactam and heptyl α-D-mannopyranoside. Further molecular dynamic simulation studies were carried out to assess the stability of dithymoquinone-target protein complexes via RMSD, Rg, SASA, hydrogen bond number, and RMSF analysis. Both protein-ligand complexes were conserved and attained equilibrium at around 2.0 to 2.5 ns during 10 ns runs. These results suggest that active constituents of Nigella sativa, particularly dithymoquinone, might represent a plausible therapeutic strategy against resistant uropathogenic bacteria.

Preparation and Evaluation of Atorvastatin-Loaded Nanoemulgel on Wound-Healing Efficacy.

Tissue repair and wound healing are complex processes that involve inflammation, granulation, and remodeling of the tissue. The potential of various statins including atorvastatin (ATR) to improve the wound healing effect was established. The aim of this study was to formulate and evaluate the efficacy of topical application of ATR-based nanoemulgel on wound healing. The prepared formulations (ATR gel, ATR emulgel, and ATR nanoemulgel) were evaluated for their physical appearance, rheological behavior, in vitro drug release and ex vivo drug permeation. The in vivo wound healing effect was evaluated in wound-induced rats. The prepared ATR gel formulations showed good physical properties and were comparable. The release profiles of drugs from gel, emulgel, and nanoemulgel were distinct. Skin permeation potential of ATR was significantly (p < 0.05) enhanced when formulated into nanoemulgel. In vivo wound healing studies showed that ATR nanoemulgel exhibited the highest percent wound contraction. Histopathological assessment showed marked improvement in the skin histological architecture after 21 days of ATR nanoemulgel treatment. In conclusion, the data demonstrated here signify the prospective of ATR nanoemulgel as an innovative therapeutic approach in wound healing.