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The aim of this work was to prepare and optimize mucoadhesive nanostructured lipid carrier (NLC) impregnated with fluconazole for better management of oral candidiasis. The NLCs were fabricated using an emulsification/sonication technique. The nanoparticles consisted of stearic acid, oleic acid, Pluronic F127, and lecithin. Box-Behnken design, artificial neural networking, and variable weight desirability were employed to optimize the joint effect of drug concentration in the drug/lipid mixture, solid lipid concentration in the solid/liquid lipid mixture, and surfactant concentration in the total mixture on size and entrapment. The optimized NLCs were coated with chitosan. The nanoparticles were characterized by surface charge, spectroscopic, thermal, morphological, mucoadhesion, release, histopathological, and antifungal properties. The nanoparticles are characterized by a particle size of 335 ± 13.5 nm, entrapment efficiency of 73.1 ± 4.9%, sustained release, minor histopathological effects on rabbit oral mucosa, and higher fungal inhibition efficiency for an extended period of time compared with fluconazole solution. Coating the nanoparticles with chitosan increased its adhesion to rabbit oral buccal mucosa and improved its anti-candidiasis activity. It is concluded that mucoadhesive lipid-based nanoparticles amplify the effect of fluconazole on

There are many synthetic drugs in literature have been utilized in healing of the wounds although the natural product specially antioxidants can offer similar if not better biological activity in t...

The objective of the current work was to develop and evaluate suppository dosage form in order to improve ranitidine bioavailability as a substitute to the oral administration. Suppocire (different grades), Witepsol W25 and polyethylene glycol (PEG) were used as suppository bases and prepared by molding method. The prepared formulations were examined for hardness, disintegration time, melting point, content uniformity, drug release, stability and bioavailability. The hardness ranged from 3.82 to 12.53 kg and disintegration time from 13.32 to 28.22 min. The melting points of fatty bases had values from 33.94 to 36.82±0.36ºC while PEG based suppositories melting points were directly proportional chain length. Higher content uniformity was observed in PEG based suppositories due to easy incorporation of RT into water soluble base. Release was affected by hydroxyl value and molecular weight (in cases of fatty and PEG bases respectively). All formulations were relatively stable after 12 months. In vivo studies of all formulations exhibited double peak phenomena. PEG based formula (S8) showed significant higher Cmax (10.05±1 μg/ml) and AUC0-12 (58.313±3.9 µg.h/mL) than fatty bases and oral solution. In conclusion, rectal administration of S8 could be prepared as an alternative to the oral dosage form to improve bioavailability and overcome the first-pass metabolism.

Although it is a front-line in tuberculosis treatment, rifampicin (RF) exhibits poor oral bioavailability and hepatotoxicity. Rectal mucoadhesive and in situ rectal gels were developed to overcome drug drawbacks. A RF/polyethylene glycol 6000 co-precipitate was first prepared in different ratios. Based on the drug solubility, the selected ratio was investigated for drug/polymer interaction and then incorporated into in situ rectal gels using Pluronic F127 (15%) and Pluronic F68 (10%) as a gel base and mucoadhesive polymers (HPMC, sodium alginate and chitosan). The formulations were assessed for gelation temperature and gel strength. The selected formulation was investigated for in vivo assessments. The results showed that a 1:1 drug/polymer ratio exhibited satisfying solubility with the recorded drug/polymer interaction. Depending on their concentrations, adding mucoadhesive polymers shifted the gelation temperature to lower temperatures and improved the gel strength. The selected formulation (F4) did not exhibit any anal leakage or marked rectal irritation. Using a validated chromatographic analytical method, F4 exhibited higher drug absorption with a 3.38-fold and 1.74-fold higher bioavailability when compared to oral drug suspension and solid suppositories, respectively. Toxicity studies showed unnoticeable hepatic injury in terms of biochemical, histopathological and immunohistochemical examinations. Together, F4 showed a potential of enhanced performance and also offered lower hepatic toxicity, thus offering an encouraging therapeutic alternative.

Long-acting preparations containing the antipsychotic paliperidone for intramuscular injection has drawn considerable attention to achieve harmless long-term treatment. This study aimed to develop paliperidone loaded polycaprolactone (PCL) nanoparticles and investigate the influence of PCL/drug ratio, stabilizer type, and chitosan coating on physicochemical properties, protein adsorption, and cellular toxicity. Results showed that chitosan coating produced enlarged particle sizes, shifted the surface charges from negative into positive and did not influence encapsulation efficiencies. Chitosan coating relatively sustained the drug release especially in pluronic stabilized formulations. Pluronic F127 based formulations exhibited the least protein adsorption (384.3 μg/mL). Chitosan coating of Tween 80 and polyvinyl alcohol stabilized formulations significantly (p < 0.05) increased protein adsorption. Cellular viability was concentration-dependent and negatively affected by stabilizers. All formulations did not show cellular death at 1.56 μg/mL. Inflammatory responses and oxidative stress were less affected by Tween 80 compared with other stabilizers. Chitosan minimized all aspects of cellular toxicity. Collectively, stabilizer type and chitosan coating play critical roles in developing safe and effective long-acting PCL nanoparticles intended for parenteral drug delivery. The coated formulations containing Tween 80 and Pluronic F127 as stabilizers are warranted a future in vivo study to delineate its safety and efficacy profiles.

This study aims to overcome most of the obstacles that face oral administration of progesterone. Fatty alcohols (cetyl, cetostearyl and 1:1 mixture) containing NLCs were thought to be one of the most relevant systems based on progesterone drawbacks as acid sensitivity and poor solubility. Formulations were prepared characterized for physicochemical evaluation, in vitro release, in vitro stability in gastric fluid, short term stability, interaction possibility and ex vivo permeation studies. The results showed nanorange particle size with major influence of fatty alcohol concentration. In vitro stability in gastric fluid and release results suggested protection of formulation from gastric environment with controlling the drug release as a function of fatty alcohol concentration. Infrared and thermal analyses showed interaction among fatty alcohol, stearic acid and progesterone. Ex vivo results showed that formulations significantly (p

Luteolin is a natural drug used as an antioxidant and anti-inflammatory, but unfortunately, it possesses low water solubility, which hinders its delivery via the skin. The main objective of this study was to prepare a luteolin-loaded nanosuspension by the antisolvent precipitation/sonication technique and study the effects of four stabilizers (two nonionic stabilizers, Pluronic F127 and Tween 80, and two polymeric stabilizers, HPMC and alginate) on the physicochemical properties of the prepared formulations. The selected formulations were incorporated into a gel base to evaluate their skin permeability and anti-inflammatory efficacy. The particle size was in the nanosize range (in the range from 468.1 ± 18.6 nm to 1024.8 ± 15.9 nm), while the zeta potential was negative and in the range from −41.7 ± 6.3 mV to −15.3 ± 1.9 mV. In particular, alginate-stabilized nanosuspensions showed the smallest particle size, the highest zeta potential value, and excellent stability due to the dual stabilizing effects (electrostatic and steric effects). The DSC results revealed a less crystalline structure of luteolin in lyophilized NS2 and NS12. Formulations stabilized by 1% Pluronic (NS2) and 2% alginate (NS12) were incorporated into a carbopol 940 gel base and showed good organoleptic character (homogenous with no evidenced phase separation or grittiness). In vitro dissolution studies showed that NS12 enhanced luteolin release rates, indicating the effect of particle size on the drug release pattern. On the other hand, NS2 showed enhanced skin permeability and anti-inflammatory effect in a carrageenan-induced paw edema model, revealing the surface activity role of the stabilizers. In conclusion, while alginate increased the nanosuspension stability by means of dual stabilizing effects, Pluronic F127 improved the skin delivery and pharmacodynamic efficacy of luteolin.

Luteolin is a valuable natural drug for the treatment of oxidative stress associated diseases, but its use is hindered by gastric instability and poor bioavailability. Given that hybrid polymeric nanoparticles may have potential applications in the design of oral drug delivery systems, this study aims to develop luteolin loaded hybrid polylactic acid/Eudragit L100 nanoparticles. By nanoprecipitation, different formulations were prepared, optimized and characterized in terms of physicochemical properties, stability and in vivo performance. The optimum formulation presented particle size of 452.23 ± 22.4 nm, zeta potential of 0.92 mV ± 0.04, entrapment efficiency of 71.02 ± 14.6% and loading efficiency of 11.21 ± 3.1%, in accordance with the values predicted created by Box-Behnken design. In vitro, the system was capable of protection of luteolin in simulated gastric fluid, while a release study confirmed the controlled luteolin release pattern. Interaction between system components was verified through infrared and thermal analysis. The maximum plasma concentration of luteolin in the optimized formulation was significantly improved (212.2 %, p

The main objective of this study was to prepare and characterize oleogel as potential carrier for quercetin skin delivery. The formulations were prepared by adding olive oil (5–30%) to Pluronic F127 hydrogel and were evaluated for particle size, zeta potential, viscosity in vitro quercetin release and stability, and were compared with that of Pluronic F127 hydrogel. The selected formulation was characterized for its interaction possibility, ex vivo skin permeation and skin histological changes and safety. The particle sizes ranged from 345.3 ± 5.3 nm to 401.5 ± 2.8 nm, and possessed negative charges. The viscosities of the formulations were found in the range of 6367–4823 cps with inverse proportionality to olive oil percentage while the higher percentages showed higher quercetin release. Percentages of 25% and 30% olive oil showed instability pattern under the conditions of accelerated stability studies. Differential scanning calorimetry verified the existence of quercetin in micellar aggregation and the network in the case of hydrogel and oleogel respectively. Ex vivo skin permeation showed an improved skin permeation of quercetin when 20% olive oil containing oleogel was used. Skin histology after 10 days of application showed stratum corneum disruption and good safety profile. Based on these findings, the proposed oleogel containing 20% olive oil denotes a potential carrier for topical delivery of quercetin.

This study focuses on the effect of different flexible liposomes containing sodium cholate, Tween 80, or cineol on skin deposition of carboxyfluorescein (CF). Size distribution, morphology, zeta potential, and stability of the prepared vesicles were evaluated. The influence of these systems on the skin deposition of CF utilizing rat skin as membrane model was investigated. Results showed that all of the investigated liposomes had almost spherical shapes with low polydispersity (PDI In vitroskin deposition data showed that flexible liposomes gave significant deposition of CF on the skin compared to conventional liposomes and drug solutions. This study revealed that flexible liposomes, containing cineole, were able to deliver higher amount of CF suggesting that the hydrophilic drugs delivery to the skin was strictly correlated to the vesicle composition.

Khaled AG ShalabyOpthamology Department, Al-Azhar University, Cairo, Egypt; Chief Vitreoretinal Service, Dr Soliman Fakeeh Hospital, Jeddah, Saudi ArabiaAbstract: Relaxing retinotomies and retinectomies are used in the presence of retinal shortening resulting from retinal incarceration or fibrous proliferation and contraction that prevents contact of the retina with the retinal pigment epithelium. The peripheral retina is usually cut or excised to preserve function of the posterior retina which is more visually significant.Objective: To investigate the techniques, therapeutic effects, indications, and complications of relaxing retinotomies and retinectomies for complicated retinal detachment with severe proliferative vitreoretinopathy (PVR).Methods: Thirty eight eyes of 38 patients of complicated retinal detachment with severe PVR were recruited for a noncomparative retrospective study. They were operated on and followed-up for at least six months. The operative technique included buckling, vitrectomy, peeling, relaxing retinotomy and/or retinectomy, intraocular tamponade, and laser treatment.Results: Retina was reattached in 34 (89.5%) eyes in operations. Retinal detachment was recurrent in seven eyes in follow-up, in which the retina was reattached again in two eyes by a second operation. The final success rate was 76.3% (29 eyes out of 38 eyes). Visual acuity was perception of light with bad projection in 35 (92%) eyes and hand motion in three (8%) eyes before operation. Visual acuity was better than 4/60 in 23 eyes (60.5%) after operation. The complications included iatrogenic retinal breaks, bleeding from the retinotomy site, hypotony, and recurrent fibrous proliferation from the retinotomy site.Conclusion: Retinotomy and retinectomy can improve the curative effect of complicated retinal detachment. There are potentially serious complications of these maneuvers and they should not be performed if less aggressive measures will suffice.Keywords: relaxing retinotomy, retinectomy, proliferative vitreoretinopathy, recurrent retinal detachment, iatrogenic retinal breaks, intraoperative hemorrhage, intraocular tamponade, hypotony