Nanocarriers for the treatment of glioblastoma multiforme: A succinct review of conventional and repositioned drugs in the last decade.

Glioblastoma multiforme is a very combative and threatening type of cancer. The standard course of treatment involves excising the tumor surgically, then administering chemotherapy and radiation therapy. Because of the presence of the blood-brain barrier and the unique characteristics of the tumor microenvironment, chemotherapy is extremely difficult and has a high incidence of relapse. With their capacity to precisely target and transport therapeutic medications to the tumor while overcoming the challenges provided by invasive and infiltrative gliomas, nanocarriers offer a potentially beneficial treatment option for gliomas. Drug repositioning or, in other words, finding novel therapeutic uses for medications that have received approval for previous uses has also recently emerged to provide alternative treatments for many diseases, with glioblastoma being among them. In this article, our goal is to shed light on the pathogenesis of glioma and summarize the proposed treatment approaches in the last decade, highlighting how combining repositioned drugs and nanocarriers technology can reduce drug resistance and improve therapeutic efficacy in primary glioma.

Visible active narrow/narrow band gap CuO/Cu2SnS3 nanoheterostructures as efficient nanophotocatalysts.

Binary metal oxide/ternary metal sulphide based nanoheterostructures, such as CuO/Cu2SnS3, were prepared via a modified hydrothermal route. The prepared nanoheterostructures were characterized using scanning electron microscopy, x-ray powder diffractometer, XPS, ultraviolet-visible spectroscopy, isoelectric point, and Brunauer-Emmett-Teller techniques. The XPS results revealed the successful incorporation of Cu+/Cu2+ with different ratios. The prepared heterostructures were tested as solar active photocatalysts for Methylene Blue (MB) photodegradation. The CuO/Cu2SnS3 (20% Cu2SnS3/80% CuO) photocatalytic results exhibited a high photodegradation efficiency (90%) after 60 min. In addition, the photonic efficiency values (ζ) were calculated to be 15.9%, 44%, and 61.4% for CuO, Cu2SnS3, and CuO/Cu2SnS3 nanoheterostructures, respectively. In addition, the reactive oxidative species were detected by the trapping experiments to get a clear insight about the photocatalytic reactivity factors. Total organic carbon (TOC) was conducted to confirm the safe photodegradation of MB dye without the formation of colorless hazardous (95.5% TOC removal). Based on the electronic band structure, the mechanism of photodegradation was investigated. The currently investigated heterostructure system is narrow/narrow bandgap, which fulfills the two contradictory conditions in terms of high solar photocatalytic activity and overcomes the rapid recombination process.

Eutectic phase transition during tablet manufacture: effect of melting point of eutectic forming drug.

The aim was to investigate eutectic transition during tableting and storage. Mixtures of lidocaine and series of NSAIDs with increasing melting point were used as model systems to guide formulators to scaleup eutectic forming materials gaining enhanced dissolution while avoiding deleterious physical changes. Physical mixtures of NSAIDs with lidocaine were prepared at eutectic forming ratio. These were directly compressed, dry co-ground before compression, or compressed after wet granulation. Dissolution of tablets was compared to corresponding dry co-ground mixture. Thermograms of direct compressed tablet were compared to co-ground mixture and pure compound. Stability of direct compressed tablets was assessed. Tableting initiated eutexia which enhanced dissolution of NSAIDs. Eutexia was associated with tablet softening in case of low melting point ketoprofen and aceclofenac. Wet granulation hastened eutexia developing unacceptable tablet in case ketoprofen and aceclofenac. Tablets prepared by direct compression of physical mixtures underwent gradual eutectic transition upon storage with the magnitude of eutectic transition reducing with increased melting point of NSAIDs. Ketoprofen was physically unstable but aceclofenac degraded chemically as well. Tenoxicam and meloxicam tablets were physically and chemically stable. Direct compression after physical mixing is the best tableting technique, but low melting point drugs should consider different strategy before compression.

Application of Design of Experiment in the Optimization of Apixaban-Loaded Solid Lipid Nanoparticles: In Vitro and In Vivo Evaluation.

Solid lipid nanoparticles (SLnPs) are usually utilized as lipid-based formulations for enhancing oral bioavailability of BCS class IV drugs. Accordingly, the objective of this work was to investigate the effect of formulation and processing variables on the properties of the developed SLnPs for oral delivery of apixaban. Randomized full factorial design (24) was employed for optimization of SLnPs. With two levels for each independent variable, four factors comprising both formulations and processing factors were chosen: the GMS content (A), the Tween 80 content (B), the homogenization time (C), and the content of poloxamer 188 used (D). The modified hot homogenization and sonication method was employed in the formulation of solid lipid nanoparticles loaded with apixaban (APX-SLnPs). The size of APX-SLnPs formulations was measured to lie between 116.7 and 1866 nm, polydispersity index ranged from 0.385 to 1, and zeta potential was discovered to be in the range of - 12.6 to - 38.6 mV. The entrapping efficiency of APX-SLnPs formulations was found to be in the range of 22.8 to 96.7%. The optimized formulation was evaluated in vivo after oral administration to rats. Oral administration of APX-SLnPs resulted in significant prolongation in bleeding time compared with both positive and negative control. This indicates the ability of this system to enhance drug therapeutic effect either by increasing intestinal absorption or trans-lymphatic transport. So, this study highlighted the capability of SLnPs to boost the pharmacological effect of apixaban.

Melting point depression for enhanced dissolution rate of eslicarbazepine acetate.

BACKGROUND: Eslicarbazepine acetate (ESL) is antiepileptic agent which is approved for use as single therapy or in combination with other drugs. However, it suffers from poor oral bioavailability. Modulation of drug crystallinity can be utilized as an approach for enhancing drug dissolution. OBJECTIVE: Accordingly, the aim of this study was to investigate possible eutectic system formation between eslicarbazepine with either tartaric acid or citric acid. METHODOLOGY: Eslicarbazepine acetate was subjected to wet co-grinding with tartaric acid or citric acid at different molar ratios. The prepared formulations were assessed using Fourier-transform infrared (FTIR), X-ray powder diffraction (XRPD), differential scanning calorimetry in addition to dissolution studies. RESULTS: The characterization techniques confirmed eutectic system formation with tartaric and citric acid with the optimum molar ratio for eutexia being 1:1 for both substances. Development of eutectic systems significantly enhanced the dissolution rate of ESL. Increasing the ratio of tartaric acid higher than the optimum ratio for eutexia resulted in additional increase in drug dissolution rate. This suggested the impact of pH modification on drug dissolution rate. The enhanced dissolution rate in case of the formulations containing ESL and citric acid was accredited to combined effect of eutaxia and pH modulation. These explanations were proven from investigating the dissolution rate of the physical mixtures which were inferior in their dissolution rate compared with the prepared formulations. CONCLUSION: co-processing of ESL with either citric acid or tartaric acid resulted in hastened dissolution rate which was accredited to combined effect of eutexia with pH modification.

Lopinavir-menthol co-crystals for enhanced dissolution rate and intestinal absorption.

Lopinavir is an antiretroviral, antiparasitic agent and recently utilized in treatment of COVID-19. Unfortunately, lopinavir exhibited poor oral bioavailability due to poor dissolution, extensive pre-systemic metabolism, and significant P-glycoprotein intestinal efflux. Accordingly, the aim was to enhance dissolution rate and intestinal absorption of lopinavir. This employed co-processing with menthol which is believed to modify crystalline structures and inhibit intestinal efflux. Lopinavir was mixed with menthol at different molar ratios before ethanol assisted kneading. Formulations were evaluated using FTIR spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and dissolution studies. Optimum ratio was utilized to assess lopinavir intestinal permeability. This employed in situ rabbit intestinal perfusion technique. FTIR, DSC and XRD indicated formation of lopinavir-menthol co-crystals at optimum molar ratio of 1:2. Additional menthol underwent phase separation due to possible self-association. Co-crystallization significantly enhanced lopinavir dissolution rate compared with pure drug to increase the dissolution efficiency from 24.96% in case of unprocessed lopinavir to 91.43% in optimum formulation. Lopinavir showed incomplete absorption from duodenum and jejuno-iliac segments with lower absorptive clearance from jejuno-ileum reflecting P-gp efflux. Co-perfusion with menthol increased lopinavir intestinal permeability. The study introduced menthol as co-crystal co-former for enhanced dissolution and augmented intestinal absorption of lopinavir.

The Development and Evaluation of Phase Transition Microemulsion for Ocular Delivery of Acetazolamide for Glaucoma Treatment.

The aim of this study was to develop microemulsion (ME) formulation with possible phase transition into liquid crystals upon ocular application to enhance acetazolamide bioavailability. Pseudoternary phase diagrams were constructed using olive oil or castor oil (oily phase), Tween 80 (surfactant), and sodium carbonate solution (aqueous phase). Microemulsion and liquid crystal (LC) formulations were selected from the constructed phase diagrams and were evaluated for rheological properties and in vitro drug release. The efficacy of the developed formulations in reducing intraocular pressure (IOP) was assessed in vivo. In vitro release study showed slower release rate from LC and ME compared with drug solution with the release from LC being the slowest. Ocular application of acetazolamide ME formulations or aqueous solution resulted in significant reduction in IOP from baseline. The recorded Tmax values indicated faster onset of action for acetazolamide aqueous solution (1 h) compared with ME systems (3 h). However, the duration of action was prolonged and the reduction in IOP continued for up to 10 h in case of MEs, while that of aqueous solution was only for 4-5 h. The study suggested ME formulations for ocular delivery of acetazolamide with enhanced efficacy and prolonged duration of action.

Niosomal versus nano-crystalline ivermectin against different stages of Trichinella spiralis infection in mice.

Ivermectin (IVM) is one of the competitive treatments used for trichinellosis. However, several studies linked its efficacy with early diagnosis and administration to tackle the intestinal phase with limited activity being recorded against encysted larvae. The aim of this study was to employ niosomes for enhancing effectiveness of oral IVM against different stages of Trichinella spiralis (T. spiralis) infection with reference to nano-crystalline IVM. Mice were randomized into four groups: group Ι, 15 uninfected controls; group ΙΙ, 30 infected untreated controls; group ΙΙΙ, 30 infected nano-crystalline IVM treated, and group ΙV, 30 infected niosomal IVM treated. All groups were equally subdivided into 3 subgroups; (a) treated on the 1st day post infection (dpi), (b) treated on the 10th dpi, and (c) treated on the 30th dpi. Assessment was done by counting adult worms and larvae plus histopathological examination of jejunum and diaphragm. Biochemical assessment of oxidant/antioxidant status, angiogenic, and inflammatory biomarkers in intestinal and muscle tissues was also performed. Both niosomes and nano-crystals resulted in significant reduction in adult and larval counts compared to the infected untreated control with superior activity of niosomal IVM. The superiority of niosomes was expressed further by reduction of inflammation in both jejunal and muscle homogenates. Biochemical parameters showed highly significant differences in all treated mice compared to infected untreated control at different stages with highly significant effect of niosomal IVM. In conclusion, niosomal IVM efficacy exceeded the nano-crystalline IVM in treatment of different phases of trichinellosis.

Histological and biochemical studies on effect of Sofosbuvir (Sovaldi) on adult male albino rat kidney.

Sofosbuvir (sovaldi) is the backbone of many anti-HCV drugs. We aimed to demonstrate the effect of sofosbuvir on the adult male albino rat kidney. Sixty adult male albino rats were used. The animals were divided equally into 2 main groups (I and II), and each group was divided equally into 3 subgroups (A, B, and C). In group I (control group), each rat was gavaged 0.5 ml distilled water daily for 4 weeks. In group II (sofosbuvir treated group), each albino rat was gavaged 0.5 ml distilled water containing 7.2 mg sofosbuvir daily for 4 weeks. The rats were sacrificed at the end of the 4th week (subgroups IA and IIA), 6th week (subgroups IB and IIB), and 8th week (subgroups IC and IIC) from the start of the treatment. The kidneys were used for histological study while blood samples were used for biochemical study. The obtained data were statistically analyzed. Sofosbuvir (sovaldi) induced pathological changes that gave the criteria of acute Kidney injury in the adult male albino rats. The pathological changes were confirmed by elevation of serum level of urea and creatinine. After 2 and 4 weeks of drug withdrawal, the kidney incompletely recovered. We concluded that sofosbuvir induced criteria of acute tubular injury in the kidney of the adult male albino rats. This renal injury was proved by histological and biochemical studies. These insults were incompletely reversible after the end the treatment.

Nanostructured lipid carriers for enhanced in vitro and in vivo schistosomicidal activity of praziquantel: effect of charge.

WHO considers praziquantel (PZQ) as the drug of choice for treatment of Schistosoma mansoni infection but this requires high dose due to poor solubility and first pass metabolism. The aim of this work was to optimize nanostructured lipid carriers (NLCs) for enhanced PZQ oral delivery. The optimization involved testing the effect of surface charge of NLCs. NLCs comprised precirol ATO as solid lipid with oleic acid, Span 60 and Tween 80 as liquid components. Dicetyl phosphate and stearyl amine were the negative and positive charging agents, respectively. NLCs were prepared by microemulsification technique and were characterized. The schistosomicidal activity of PZQ loaded NLCs was monitored in vitro and in vivo using infected mice. PZQ showed high entrapment efficiency in all types of NLCs (ranged from 93.97 to 96.29%) with better PZQ loading in standard NLCs. This was clarified by thermal analysis which reflected displacement of PZQ by charging agents. In vitro schistosomicidal study revealed the superiority of PZQ loaded positively charged NLCs (LC50 and LC95 equal 0.147 and 0.193 µg/ml respectively) with traditional and negatively charged NLCs being inferior to simple PZQ solution after short incubation period. Scanning electron micrographs showed that PZQ loaded positively charged NLCs resulted in more intense ultrastructural changes in worms. The superiority of positively charged NLCs was confirmed by in vivo assessment as they showed better improvement in histopathological features of the liver of the infected mice compared with other formulations. The study introduced positively charged NLCs as promising carriers for oral delivery of PZQ.

Co-processing of Atorvastatin and Ezetimibe for Enhanced Dissolution Rate: In Vitro and In Vivo Correlation.

Development of fixed dose combinations is growing and many of these drug combinations are being legally marketed. However, the development of these requires careful investigation of possible physicochemical changes during co-processing. This requires investigation of the effect of co-processing of drug combination in absence of excipients to maximize the chance of interaction (if any). Accordingly, the aim was to investigate the effect of co-processing of ezetimibe and atorvastatin on drugs dissolution rate. The objective was extended to in vitro in vivo correlation. Drugs were subjected to wet co-processing in presence of ethanol after being mixed at different ratios. The prepared formulations were characterized using FTIR spectroscopy, X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, and in vitro dissolution testing. These investigations proved the possibility of eutectic system formation after drugs co-processing. This was reflected on drugs dissolution rate which was significantly enhanced at dose ratio and 2:1 atorvastatin:ezetimibe molar ratio compared to the corresponding pure drugs. In vivo antihyperlipidemic effects of the co-processed drugs were monitored in albino mice which were subjected to hyperlipidemia induction using poloxamer 407. The results showed significant enhancement in pharmacological activity as revealed from pronounced reduction in cholesterol level in mice administering the co-processed form of both drugs. Besides, histopathological examinations of the liver showed marked decrease in hepatic vacuolation. In conclusion, co-processing of atorvastatin with ezetimibe resulted in beneficial eutexia which hastened the dissolution rate and pharmacological effects of both drugs.Graphical abstract.

Hypoxia-Preconditioned Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Mitigate Hypoglycemic Testicular Injury Induced by Insulin in Rats.

Hypoglycemia is a neglected metabolic disorder. Thus, we evaluated the protective effect of hypoxia-preconditioned human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on hypoglycemic testicular injury. We examined 56 testes from 28 animals: 7 rats with insulin-induced hypoglycemia (HG group), 7 hypoglycemic rats which received an intratesticular injection of hUCB-MSCs (HG-MSC group), and 14 untreated control rats. Testosterone level, testicular catalase (CAT) activity, and malondialdehyde (MDA) level were analyzed. Immunostaining for specific testicular germ and somatic cell markers was performed. Proliferating and apoptotic cells were detected by anti-PCNA and anti-caspase-3, respectively. Morphometrical data were statistically analyzed. The hypoglycemic rats showed a significant decrease in testosterone level and CAT activity and a significant increase in MDA production. Examination of histological structure and protein expression of diverse germ cell markers revealed collapsed tubules that were lined by degenerated germ cells, decreased lactate dehydrogenase type C immune expression, as well as decreased proliferating and increased apoptotic cells number in hypoglycemic testes. Injection of MSCs improved testicular biochemical parameters, preserved germ cells and somatic cells, and decreased apoptosis. In conclusion, hypoxia-preconditioned hUCB-MSCs attenuate rat testicular injury caused by insulin-induced hypoglycemia. Avoidance and rapid management of hypoglycemia are necessary to avoid significant testicular injury.

Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate the Pancreatic Changes of Chemically Induced Hypothyroidism by Carbimazole in Male Rats.

We induced hypothyroidism (HT) in male rats through chronic oral administration of carbimazole and then tested whether an i.v. injection of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) could ameliorate the HT-induced changes in pancreatic structure and function. The thyroid and pancreatic function tests, as well as total antioxidant capacity (TAC) and malondialdehyde (MDA) were estimated. The pancreatic structure was evaluated by hematoxylin and eosin (H&E) stain. Insulin protein and cleaved caspase-3 were detected immunohistochemically. The degree of apoptosis was assessed by TUNEL assay. The morphometric measurements were done by an image analyzer system and the obtained data were statistically analyzed. HT rats showed hyperglycemia associated with insulin deficiency, decreased TAC and increased MDA levels. H&E-stained sections showed that the pancreatic septa were infiltrated with acidophilic material. Some acini were vacuolated while others showed depleted acidophilia and dilated lumina. Spindle-shaped cells were accumulated within deformed islets in HT rats. The positive reaction with anti-cleaved caspase-3 was exclusively noted in the cytoplasm of islet cells with no immunostaining reaction in the acinar and ductal cells, whereas the positively stained nuclei with TUNEL were demonstrated in the islet and acinar cells. A significant increase in the apoptotic index % of both markers was detected. Injection of BM-MSCs in HT rats restored all biochemical indicators of disturbed pancreatic function to normal level and improved pancreatic structure, resulting in a clear septa and normal appearance of acini and islets. In conclusion, many of the significant structural and func tional pancreatic alterations detected in HT rats were ameliorated after the injection of BM-MSCs. These data demonstrate the ability of BM-MSCs to repair pancreatic disturbances. Further studies on humans are necessary to determine the potential clinical applications of BM-MSCs.

Factorial design optimization of micelle enhanced synchronous spectrofluorimetric assay of Omarigliptin: Applied to content uniformity testing and in vitro drug release.

A micelle enhanced spectrofluorimetric method was developed for determination of Omarigliptin (OMG) based on its native fluorescence behavior. The interaction of OMG with surfactants and macromolecules was studied. In aqueous solution, the relative fluorescence intensity (RFI) of OMG was enhanced by 24% in the presence of Tween 80 at pH 3.5. The optimal conditions for the micelle enhanced fluorescence were attained by Minitab® program using Plackett-Burman factorial design. Pareto chart, contour plots and surface plots were used to exclude the insignificant variables and optimize the significant factors. The spectrofluorimeter was operated under synchronous mode using ∆λ = 30 nm and recording the RFI of the intense narrow band at 267 nm for OMG in 0.5% w/v Tween 80 + 0.2 M acetate buffer (pH 3.5) system using water as diluent. Using synchronous scan mode offered many advantages including considerable reduction of spectral overlap and enhanced linearity of the calibrators. Validation parameters were satisfied over the concentration range 0.1-2 µg/ml. The developed method was the first analytical procedure for OMG assay in Marizev® tablets. Moreover, content uniformity testing and in vitro drug release of tablets were performed.

Xylitol as a potential co-crystal co-former for enhancing dissolution rate of felodipine: preparation and evaluation of sublingual tablets.

Dissolution enhancement is a promising strategy for improving drug bioavailability. Co-crystallization of drugs with inert material can help in this direction. The benefit will become even greater if the inert material can form co-crystal while maintaining its main function as excipient. Accordingly, the objective of the current study was to investigate xylitol as a potential co-crystal co-former for felodipine with the goal of preparing felodipine sublingual tablets. Co-crystallization was achieved by wet co-grinding of the crystals deposited from methanolic solutions containing felodipine with increasing molar ratios of xylitol (1:1, 1:2 and 1:3). The developed co-crystals were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) before monitoring drug dissolution. These results reflected the development of new crystalline species depending on the relative proportions of felodipine and xylitol with complete co-crystallization of felodipine being achieved in the presence of double its molar concentration of xylitol. This co-crystal formulation was compressed into sublingual tablet with ultrashort disintegration time with subsequent fast dissolution. Co-crystal formation was associated with enhanced dissolution with the optimum formulation producing the fastest dissolution rate. In conclusion, xylitol can be considered as a co-crystal co-former for enhanced dissolution rate of drugs.

Sucralose as co-crystal co-former for hydrochlorothiazide: development of oral disintegrating tablets.

Development of oral disintegrating tablets requires enhancement of drug dissolution and selection of sweetener. Co-crystallization of drugs with inert co-former is an emerging technique for enhancing dissolution rate. The benefit of this technique will become even greater if one of the sweeteners can act as co-crystal co-former to enhance dissolution and mask the taste. Accordingly, the objective of this work was to investigate the efficacy of sucralose as a potential co-crystal co-former for enhancing the dissolution rate of hydrochlorothiazide. This was extended to prepare oral disintegrating tablets. Co-crystallization was achieved after dissolving hydrochlorothiazide with increasing molar ratios of sucralose in the least amount of acetone. The co-crystallization products were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and powder X-ray diffraction. These measurements indicated that co-crystallization process started at a drug sucralose molar ratio of 1:1 and completed at 1:2. The developed co-crystals exhibited faster drug dissolution compared with the control, with co-crystal containing the drug with sucralose at 1:2 molar ratio being optimum. The later was used to prepare fast disintegrating tablets. These tablets had acceptable physical characteristics and showed fast disintegration with subsequent rapid dissolution. The study introduced sucralose as co-crystal co-former for enhanced dissolution and masking the taste.

Chemopreventive effect of Mentha piperita on dimethylbenz[a]anthracene and formaldehyde-induced tongue carcinogenesis in mice (histological and immunohistochemical study).

OBJECTIVE: Cancer chemoprevention is defined as the use of chemicals or dietary components to block, inhibit, or reverse the development of cancer in normal or pre-neoplastic tissue. Mentha extract (ME) has antioxidant and antiperoxidant properties. This study was held to investigate the protective and anticancer effect of Mentha leaves aqueous extract on oral epithelium of mice tongues. DESIGN: A total of 80 Egyptian albino mice were divided into three groups. Group I served as control (not subjected to any kind of treatment), and groups II and III were subjected to two-stage chemical carcinogenesis through topical application of dimethylbenz[a]anthracene (DMBA) followed by formaldehyde on dorsal and ventral surfaces of tongues for 9 weeks. Mentha leaves extract was administrated to group III at the same time of cancer induction. Histological changes were assessed in H&E sections at 3-week intervals. The anticarcinogenic effect of Mentha piperita was tested using immunostain with anticaspase antibody. RESULTS: The oral administration of ME reduced the appearance of dysplastic cellular changes with 61% and inhibited tumor incidence with 100%. Group I showed moderate-to-strong cytoplasmic caspase expression. At 6-week interval, group II showed weak-to-moderate caspase expression, while sections from group III showed moderate-to-strong caspase expression. High significant statistical difference in the total score of caspase 3 expression was found between specimens obtained from animals sacrificed at 6 weeks in groups I, II, and III (P = 0.001**). CONCLUSION: Our study demonstrated that Mentha piperita has inhibited the initiation and promotion of oral dysplastic lesions.

Microemulsion for simultaneous transdermal delivery of benzocaine and indomethacin: in vitro and in vivo evaluation.

This study investigated simultaneous transdermal delivery of indomethacin and benzocaine from microemulsion. Eucalyptus oil based microemulsion was used with Tween 80 and ethanol being employed as surfactant and cosurfactant, respectively. A microemulsion formulation comprising eucalyptus oil, polyoxyethylene sorbitan momooleate (Tween 80), ethanol and water (20:30:30:20) was selected. Indomethacin (1% w/w) and benzocaine (20% w/w) were incorporated separately or combined into this formulation before in vitro and in vivo evaluation. Application of indomethacin microemulsion enhanced the transdermal flux and reduced the lag time compared to saturated aqueous control. The same trend was evident for benzocaine microemulsion. Simultaneous application of the two drugs in microemulsion provided similar enhancement pattern. The in vivo evaluation employed the pinprick method and revealed rapid anesthesia after application of benzocaine microemulsion with the onset being 10 min and the action lasting for 50 min. For indomethacin microemulsion, the analgesic effect was recorded after 34.5 min and lasted for 70.5 min. Simultaneous application of benzocaine and indomethacin provided synergistic effect. The onset of action was achieved after 10 min and lasted for 95 min. The study highlighted the potential of microemulsion formulation in simultaneous transdermal delivery of two drugs.

Water in nigella oil microemulsion for enhanced oral bioavailability of linagliptin.

Linagliptin is hydrophilic antidiabetic with poor oral bioavailability due to poor permeability and pre-systemic metabolism. The objective was to assess w/o microemulsion for enhanced oral bioavailability of linagliptin. Nigella oil was used as oily phase based on its reported antidiabetic effect. Isopropyl myristate (IPM) or capryol were combined with nigella oil to impart intestinal membrane permeabilizing abilities. Pseudoternary phase diagrams were constructed utilizing nigella oil in presence and absence of isopropyl myristate or capryol as oily phase using Tween 60 as surfactant. W/O microemulsion formulations were selected from the constructed phase diagrams and linagliptin was loaded in the internal aqueous phase at a concentration of 0.5 mg/ml. The prepared formulations were physically evaluated and linagliptin in vitro release was monitored. Eventually, the in vivo hypoglycemic effect was assessed using diabetic rats. The developed microemulsions were of w/o type and exhibited Newtonian flow behavior with nigella/capryol microemulsion recording the lowest viscosity. The recorded droplet size values were 104.9, 121.2 and 86.4 nm for nigella, nigella/IPM and nigella/capryol microemulsions, respectively. All microemulsion formulations showed slower drug release rate compared with aqueous suspension with nigella/capryol microemulsion showing the highest release rate compared to other microemulsions. Release data from microemulsion best fitted to Higuchi model. In vivo oral hypoglycemic activity measurement reflected a more intensified hypoglycemic effect with rapid onset after oral ingestion of microemulsion compared to linagliptin dispersion. Nigella oil/IPM-based microemulsion was ranked as the most effective. The investigation highlighted the feasibility of w/o microemulsion for enhanced oral bioavailability of hydrophilic drugs like linagliptin.

Functionalized surface of PLGA nanoparticles in thermosensitive gel to enhance the efficacy of antibiotics against antibiotic resistant infections in endodontics: A randomized clinical trial.

Enterococcus faecalis plays the key role in endodontic infections and is responsible for the formation of biofilm on dentin, which causes a resistance against periradicular lesions treatment, consequently the aim of this study is to use nanoparticles entrapping anibacterial agents coated with chitosan that in authors previous study showed a successful in vitro biofilm inhibition, additionally incorporated in thermoresponsive gel.to benefit nanoparticles` small size, and the positive charge of their surfaces that binds with the negatively charged surface of bacterial cell causing its destruction, in addition to the sustained release pattern of the drug based nanoparticles in gel. Therefore, Ciprofloxacin hydrochloride (CIP) encapsulated in PLGA nanoparticles coated with chitosan (CIP-CS-PLGA-NPs), in addition to free CIP, were incorporated in Pluronic® 407/188 to form thermosensitive gels (F1) and (F2), respectively. The thermosensitive gels were tested with regards to rheology, gelling temperature and the release pattern of the drug. A clinical study of the efficacy of F1 and F2 as antibacterial treatments was conducted on patients followed by a comparative studies against CIP and Ca(OH)2 pastes in terms of biofilm inhibition assay and total bacterial reduction count and percent.The results revealed that F1 and F2 exhibited gelation temperature of 36.9 ± 0.3 °C and 36.0 ± 0.4 °C, viscosity was 15,000 ± 360.6 and 7023.3 ± 296.8 cP respectively. The cumulative release of F1 and F2 after 72 h was 50.03% ± 0.7345 and 77.98% ± 3.122 respectively. F1 was the most efficient treatment against recurrent E.faecalis infection in endodontics that was evident by the highest total bacterial reduction count and percent and biofilm inhibition percent that were recorded in the group treated with F1followed by the group treated with F2. Nanocarriers succeeded in carrying the drug deeply in the root canal and sustaining its effect to abolish the obstinate E. faecalis recurrent infection and its biofilm formation.