Protection of hair color with pomegranate peel extract-loaded liposomal formulation: Preparation, characterization, and ex-vivo activity studies.

BACKGROUND: Pomegranate peel extract is known as a powerful antioxidant and due to preventing oxidation, it can reduce color change of dyed hair after washing. Liposomes are vesicular systems that include lipids and can form a film on hair fibers. Delivery system and active agent have a synergistic effect on protecting hair color and reducing dyeing frequency. AIMS: This study aimed to prepare liposomes suspension as an innovative formulation of pomegranate peel extract to reduce hair color changing. METHODS: Pomegranate peel extract-loaded liposomes were prepared with lipidic film hydration method. The characterizations of formulations (F1 and F2) were defined by several parameters. The pH, particle size, polydispersity index, zeta potential, microscopical image, loading capacity (LC), and encapsulation efficiency (EE) of formulations were determined. The antioxidant capacity of formulations and actives were tested. The effect of formulations on hair color change was shown with ex-vivo studies. RESULTS: The results showed that cholesterol influenced particle size, zeta potential, and antioxidant capacity. The particle sizes of formulations were 217.71 ± 6.74 nm and 577.5 ± 1.41 nm for F1 and F2, respectively. F2 formulation had better results for zeta potential (33.8 mV) while F1 was neutral. Morphologic images confirmed vesicular structure or liposomes. The EE was found higher for F2 than F1 (F1: 57.14 and F2: 78.69). Antioxidant studies confirmed that active substance and the vesicular system had a synergistic effect on protection from oxidation. Selected formulation reduced hair color change as shown in ex-vivo tests. CONCLUSION: Pomegranate peel extract-loaded liposomes were designed for hair color protection. It was shown with this study that prepared formulations have a good color protection on hair fibers due to antioxidant properties of pomegranate peel extract and film forming effect of liposomal formulations. According to results, prepared liposomal formulations may serve as a good alternative for reducing dyeing frequency and protecting hair fibers.

Design and in vitro, in vivo evaluation of antioxidant bioadhesive gels for burn treatment.

Burn wounds are frequently encountered health problems, which need a new treatment approach especially in terms of good patient compliance. Availability of use of antioxidant agents and bio-adhesive gels in tissue healing can be an alternative as a new approach for wound healing. Antioxidant taurine containing bio-adhesive gels were prepared by using carbopol (CP) 940 and 934. Rheological and texture analyses were carried out on bio-adhesive gels for in vitro characterization. Wound model on Wistar rats was used to evaluate the in vivo evaluation of gels. Rheological and texture analyses showed that a carbopol bioadhesive gel has acceptable topically use dosage characteristics and in combination with Taurine it presented a successful wound healing effect via antioxidant parameters. In conclusion, bio-adhesive CP 940 (2%) gel containing 50 mM taurine could be promising in the treatment of burns by balancing oxidative stress.

Comparative Evaluation of Clinical Efficacy and Safety of Collagen Laminin-Based Dermal Matrix Combined With Resveratrol Microparticles (Dermalix) and Standard Wound Care for Diabetic Foot Ulcers.

This is an open, prospective, comparative parallel-arm medical device clinical study of Dermalix (Dx) in diabetic foot wounds. Dx is a 3-dimensional collagen-laminin porous-structured dermal matrix prepared and additionally impregnated with resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine-based microparticles. The aim was to evaluate the efficacy and safety of Dx, an investigational medical device, in Wagner 1 and 2 wounds in comparison to a standard wound care (SWC) that consists of irrigation and cleaning with sterile saline solution. Forty-eight patients were randomized to receive either SWC or SWC + Dx. A 4-week treatment period was followed by a 2-month follow-up without treatment. The wound area measurement, total collagen, vascular epidermal growth factor, tumor necrosis factor, interleukin 1, caspase 3, glutathione, reduced/oxidized glutathione, and lipid peroxidation levels were evaluated. At the end of 4 weeks, the percentage closures of wounds were determined as 57.82% for Dx, and 26.63% for SWC groups. Dx had a significant effect on tumor necrosis factor, caspase 3, and reduced/oxidized glutathione levels. Dx provided 2 times faster wound healing and decreased oxidative stress. Application of Dx in the first phase of wound would help the wound area heal faster with a safe profile.

An examination of carbopol hydrogel/organogel bigels of thymoquinone prepared by microwave irradiation method.

Nigella sativa L. is shown wide spread over the world and contains many useful phytochemicals. Much of the biological activity of the seeds has been shown due to the presence of thymoquinone (TQ). Its poor aqueous solubility of TQ hinders its delivery to target site. The aim of this work was to prepare TQ bigels composed of Carbopol 974 P NF (C974) in PEG 400 (organogel) or C974 in water (hydrogel) with microwave heating method. A novel technique, high speed homogenization followed by microwave heating, was used to prepare organogels. The pH, electrical conductivity, differential scanning calorimetry, rheological properties, and morphological structure of the formulations have been evaluated, and the effect of microwave on drug content and TQ antioxidant activity has been investigated. The bigels of TQ were successfully produced via high-speed homogenization followed by microwave-assisted heating for the first time in this study. Highly lipophilic TQ was successfully dissolved in organogel, and it was not affected from the microwaves. It can be stated that microwave heating is a promising method to obtain C974 organogels and thus bigels with appropriate above indicated investigated physicochemical characteristics. The time and energy consumption could be decreased with microwave-assisted heating, especially for gel preparation in the field of pharmaceuticals.

OPHTHALMIC APPLICATIONS of SLN and NLC.

BACKGROUND: The eyes are among the most readily accessible organs in terms of location in the body, yet drug delivery to eye tissues is particularly problematic. The anatomy, physiology and biochemistry of the eye limit the ophthalmic delivery of drugs. Numerous strategies in ophthalmic drug delivery have been made to expand the bioavailability and to prolong the remaining time of drugs treated topically to eye. METHODS: Designing a novel delivery vehicles that can proficiently target the diseased eye tissue, generate high drug levels, and keep sustained and effective concentrations with no or minimum side effects is the main concentration of present examination. One of the encouraging approaches currently is the use of lipidic nanoparticle vehicles categorized by a submicron-meter dimension. Due to their properties and numerous advantages, solid lipid nanoparticles and nanostructure lipid carriers are promising systems for ocular drug delivery. CONCLUSION: The focus of this review is on the recent developments in ophthalmic lipid nanoparticles, the rationale for their use, drug loaded SLNs and NLCs, and the characteristic advantages, limitations of this system and recent studies.

Modification of solid lipid nanoparticles loaded with nebivolol hydrochloride for improvement of oral bioavailability in treatment of hypertension: polyethylene glycol versus chitosan oligosaccharide lactate.

Nebivolol (NB)-loaded solid lipid nanoparticles (SLNs) were prepared and modified with chitosan oligosaccharide lactate (COL) and polyethylene glycol (PEG) stearate for improvement of its oral bioavailability. Compritol, poloxamer and lecithin were used for the preparation of SLNs by homogenisation method. After in vitro characterisation effect of lipase, pepsin, or pancreatin on degradation and release rate were investigated. Cytotoxicity and permeation were studied on Caco-2 cells. As COL concentration increased in SLNs, size and zeta potential increased. PEG concentration was reversely proportional to particle size with no change in zeta potential. Encapsulation efficiencies (EEs) were determined as 84-98%. DSC confirmed solubilisation of NB in lipid matrix. A sustained release with no burst effect was determined. The presence of enzymes affected the release. SLNs did not reveal cytotoxicity and highest permeability was obtained with PEG modification. PEG-modified SLNs could be offered as a promising strategy for oral delivery of NB.

Novel nanostructured lipid carrier-based inserts for controlled ocular drug delivery: evaluation of corneal bioavailability and treatment efficacy in bacterial keratitis.

OBJECTIVES: The aim of the present study was to develop novel ofloxacin (OFX)-loaded nanostructured lipid carrier (NLC)-based inserts for ocular application for treatment of bacterial keratitis. METHODS: NLC loaded with 0.3% OFX was prepared by means of high shear homogenization and 0.75% chitosan oligosaccharide lactate (COL) was added. Glycerin or PEG 400 at the range of 1 - 15% was added to NLCs as plasticizers and inserts were developed by solvent casting evaporation. Characterization, in vitro release, microbiological, ex vivo and in vivo studies were performed. RESULTS: The inserts developed with the addition of glycerin (Ins3OFX) was found as optimal. The kinetic studies revealed that the release of Ins3OFX was a combination of diffusion and swelling. Ins3OFX was more bioadhesive in texture profile analysis studies. In the in vivo studies performed with rabbits, the pre-ocular retention time was enhanced up to 24 h and Cmax was increased almost six times in comparison with commercial. The rabbits were infected with Staphylococcus aureus and keratitis was confirmed. This group was treated with Ins3OFX and they recovered in 7 days with no significant sign of conjunctival redness and corneal opacity. CONCLUSION: NLC-based inserts developed with COL and glycerin may be offered as appropriate vehicles for ocular delivery.

Preparation and in vitro-in vivo evaluation of ofloxacin loaded ophthalmic nano structured lipid carriers modified with chitosan oligosaccharide lactate for the treatment of bacterial keratitis.

The objective of this study was to explore the potential of the nanostructured lipid carriers (NLCs) modified with chitosan oligosaccharide lactate (COL) for topical ocular application. Ofloxacin (OFX) loaded NLCs were prepared by microemulsion or high shear homogenization methods. For combination of NLCs Compritol HD5 ATO was used as solid lipid, oleic acid as liquid lipid, Tween 80 as surfactant, ethanol as co-surfactant. The optimum NLCs was modified with 0.75% COL. The properties of NLCs in the absence or presence of OFX (0.3%) were characterized as zeta potential, particle size, viscosity and pH, TEM, drug loading, encapsulation efficiency and anti-microbial properties. Ex-vivo penetration/permeation studies were performed with rabbit cornea in Franz-diffusion cells. The penetration rate of OFX from NM-COL4OFX and NH-COL4OFX were significantly higher than commercial solution. Based on the selected formulations, in vivo tests were carried out by eye-drop instillation of NLCs in rabbit. The addition of COL improved the preocular residence time, controlled the drug release and enhanced the corneal bioavailability. In conclusion, OFX COL modified NLCs prepared by high shear homogenization method could be offered as a promising strategy for ocular drug delivery.

Novel ofloxacin-loaded microemulsion formulations for ocular delivery.

PURPOSE: The aim of this study was to prepare a novel oil-in-water microemulsion of ofloxacin (OFX) for topical ocular application. METHODS: Pseudo-ternary phase diagrams were constructed for combination of oleic acid as oil phase, Tween 80 as surfactant, ethanol as co-surfactant, and 0.5 N NaOH solutions as aqueous phase. The optimum microemulsion was modified with 0.75% chitosan oligosaccharide lactate (COL). The properties of microemulsions in the absence or presence of OFX (0.3%) were measured, such as electrical conductivity, droplet size, viscosity, and pH. The in vitro release study was carried out using the dialysis bag method. Ex vivo permeability studies were performed with rabbit cornea in Franz-diffusion cells. Sterility, minimum inhibition concentration (MIC), and antibacterial activity studies were conducted microbiologically. The preocular residence time and efficacy against bacterial keratitis was compared with a commercial (C) solution via in vivo studies. RESULTS: M2OFX modified with 0.75% COL showed slower release than M1OFX, which does not contain COL. The permeation rate of OFX from M1OFX was significantly higher than M2OFX and the C solution. The formulations were sterile and MIC values were the same for both. M2OFX, which contains 0.75% COL, performed higher antibacterial activity than M1OFX. The preocular residence time was improved by microemulsion in comparison to solution; the addition of COL did not make a significant difference. In total, 8 rabbits gave better results with M1OFX, whereas 4 gave similar scores to commercial solution-applied rabbits. CONCLUSION: In conclusion, OFX microemulsions could be offered as a promising strategy for ocular drug delivery.

A novel preparation method for organogels: high-speed homogenization and micro-irradiation.

The aim of this work was to prepare organogels of Carbopol 974P NF (C974) in PEG 400 by using a novel technique, high-speed homogenization followed by microwave heating. Triclosan (TCS) was used as a model drug. C974, at concentrations ranging between 2% and 4%, was dispersed in 25 ml of PEG 400, and the dispersion was homogenised for 5 min at 24,000 rpm. The dispersion was either heated at 80°C in water bath under mechanic stirring at 200 rpm or exposed to micro-irradiation (1,200 W/1 h) for 2 min. The formulations prepared with both methods performed a well-structured gel matrix characteristic at 3% and 4% of C974 concentrations. As the concentrations of the polymer increased, the elastic properties also increased. The viscosity profiles indicated a shear-thinning system. DSC data revealed that TCS was dissolved in gel. Skin accumulation ability of TCS had been improved by these novel organogels regardless of the preparation method. TCS was still microbiologically effective after the microwave process was applied. It was determined that microwave heating is a suitable method to obtain C974 organogels. This novel production technique developed might be promising especially in industrial scale when the dramatic reduction in the preparation time and energy were considered.

A new approach to the treatment of recurrent aphthous stomatitis with bioadhesive gels containing cyclosporine A solid lipid nanoparticles: in vivo/in vitro examinations.

AIM: To develop a suitable buccal bioadhesive gel formulation containing cyclosporine A solid lipid nanoparticles (CsA SLNs) for the treatment of recurrent aphthous stomatitis. METHODS: The suitability of the prepared formulations for buccal application was assessed by means of rheological studies, textural profile analysis, and ex vivo drug-release studies. Plastic flows, typical gel-like spectra, and suitable mechanical properties were obtained from prepared formulations. The retention time was explored in in vivo distribution studies and the effect of the gel containing CsA SLNs on the healing of oral mucosal ulceration was investigated in an animal model. In vivo distribution studies are a very important indicator of the retention time of formulations at the application site. RESULTS: Distribution studies showed that 64.76% ± 8.35% of the formulation coded "F8+SLN" remained on the buccal mucosa 6 hours after application. For the second part of the in vivo experiments, 36 rabbits were separated into three groups: the first group was treated with the gel formulation without the active agent; the second group with the gel formulation containing CsA SLNs; and the third group, used as the control group, received no treatment. Wound healing was established by scoring of the rate of wound healing on Days 3, 6, 9, and 12. Histological observations were made on the same days as the scoring studies. The bioadhesive gel formulation that included CsA SLNs increased the rate of mucosal repair significantly. CONCLUSION: This study has shown that the bioadhesive gel formulation containing CsA SLNs reported here is a promising candidate for the topical treatment of recurrent aphthous stomatitis.

Chitosan-associated SLN: in vitro and ex vivo characterization of cyclosporine A loaded ophthalmic systems.

The aim of this study was to develop cyclosporine A (CsA) loaded solid lipid nanoparticles (SLN) associated with chitosan (CS), to improve interaction and internalization in corneal cells. The SLN were prepared using high shear homogenization and ultrasound methods with CS in the aqueous phase. The lipid phase was based on Compritol or Precirol. The SLN were characterized for particle size, polydispersity index, morphology, zeta potential and encapsulation efficiency. The systems were freeze-dried to increase physical stability and trehalose was used as a cryo/lyo-protector to stabilize the SLN. The penetration and permeation properties of the SLN were assessed in vitro (cell culture) and ex vivo (excised pig cornea). The cell uptake of SLN was studied by means of confocal laser scanning microscopy. CS-associated SLN based on Compritol were biocompatible and enhanced the permeation/penetration of CsA along with a possible mechanism of internalization/uptake of the nanoparticles both in vitro and ex vivo.

In vitro release--in vivo microbiological and toxicological studies on ketoconazole lipid granules.

In some multidrug therapy programs, ketoconazole (KTZ) may be administered with some antacids that could modify its dissolution rate and reduce its absorption, thus leading to therapeutic failures. The primary aim of this study was to evaluate the influence of Compritol HD5 ATO and Compritol 888 ATO on this interaction in comparison with commercial KTZ tablets. The second aim was to prepare lipid granules of KTZ that could be an alternative to the commercial formulation. Therefore, six KTZ sustained-release granules were prepared with different lipid concentrations, because they were found to be more suitable than tablets that are dissolved only in gastric medium. The results confirmed that the dissolution rate of KTZ granules was significantly reduced in the presence of antacids. The ideal formulation was selected as granules including 5% of Compritol lipids in relation to the suitability of the target profile. Therapeutic effects of orally administered, ideal KTZ granule formulations, and commercial tablets were evaluated in vivo by the experimental model of murine vulvo-vaginal candidiasis (VVC) with and without antacids. It was found that formulations were very effective on VVC, and the therapeutic effect decreased significantly in the presence of antacids. Histopathological studies were carried out for vagina, stomach, and liver tissues and hepatoxicity was also examined. The levels of reduced glutathione (GSH) were measured to assess the oxidative stress induced by KTZ and function of the liver. It was observed that orally administered formulations of KTZ were successful in treating candidiasis in mice without irritancy in stomach. However, liver tissues were damaged. The decreased GSH levels indicated toxicity in our study. This study suggested that in vitro release and in vivo microbiological-toxicological properties of KTZ were affected by antacids and drug-excipient interactions. Lipid granules of KTZ prepared with Compritol 888 ATO could be proposed as a new KTZ solid dosage form with optimum dissolution and therapeutic characteristics.