Determination of the Toxicity Preferences of Ocular Drug Delivery System by Comparing Two Different Toxicity Bioassays.

Ocular drug delivery methods are highly favored for boosting bioavailability, patient compliance, and lower adverse effects and dose frequency. In addition to preventing adverse effects from the active ingredient, the parts of drug delivery systems must be nontoxic and nonallergic as well. Mitochondrial toxicity test (MTT) and Hen's egg chorioallantois membrane (HET-CAM) assay are the most often utilized tests based on this dilemma. The toxicity of loteprednol etabonate loaded solid lipid nanoparticles, lipid nanostructured carriers, and nanoemulsion were compared. Oleic acid, Precirol®ATO5, and Pluronic® F68 were used in the preparation. Their toxicities were evaluated by using two different toxicity tests (MTT and HET-CAM). The results suggest that there are no significant differences between the HET-CAM and MTT assays. It is noteworthy that the HET-CAM assay offers a more cost-effective and environmentally friendly alternative to the MTT assay, as it does not require cell culture and generates less toxic waste. This information may be useful to consider when selecting between the two assays.

Loteprednol-Loaded Nanoformulations for Corneal Delivery by Quality-by-Design Concepts: Optimization, Characterization, and Anti-inflammatory Activity.

Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19 nm, 82.38 nm, and 126.35 nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye.

Safety in Cosmetics and Cosmetovigilance, Current Regulations in Türkiye.

Although it is considered that cosmetics do not have side effects, studies have revealed that a significant number of consumers experience side effects. Undesirable effects arising from the use of cosmetic products have created the need for a reporting and evaluation system, which is responsible for some restrictions on the use of cosmetics ingredients and putting into cosmetic regulation effect, called cosmetovigilance. However, the new cosmetovigilance concept needs some updates to become more effective for public health. For instance, side effects related to cosmetic use have been reported more frequently recently, but this rate is still quite low. Additionally, since the current cosmetic directive does not recognize cosmeceuticals as a distinct category from cosmetics, some products named cosmetic under the laws may affect the bottom layers of dermis and cause systemic side effects. Although the manufacturers must show safety assessments to the Turkish Pharmaceutical and Medical Device Agency to get a license, after launching they do not have post-vigilance reporting to the institution, which is another problem of the system. In this review, the current cosmetovigilance system in Türkiye was discussed and some hardships encountered were criticized regarding the implementation of the system. Additionally, scientific studies are conducted on cosmetic ingredients that can have side effects and contribute to the developing cosmetovigilance concept. Because of the study, the importance of the feedback of healthcare professionals in the cosmetovigilance system, the consultancy service to be given to the consumer and patient about the contents that should be considered. Besides, there is a need for new studies to indicate the adverse reaction incidence related to cosmetics in the Turkish market. Another outcome of this review article is to understand the importance of the new regulations regarding the increase in the new active ingredients in the cosmetic market.

Development of lipid nanoparticles for transdermal loteprednol etabonate delivery.

AIM: Loteprednol etabonate (LE) is a new generation corticosteroid that is used for the treatment of inflammatory and allergic conditions of the eye. Therefore, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were attempted to improve transdermal LE delivery for the first time. METHODS: SLN and NLC were produced by hot homogenisation and ultrasonication technique. Their physical stability was monitored for 3 months of storage. Drug release and permeation of SLN and NLC through the porcine skin were investigated. RESULTS: It was determined that SLN and NLC mean particle size of 139.1 nm had a homogeneous particle size distribution (∼0.169 PI) and the mean charge was -23.6. They were found to be stable both physically and chemically at room temperature. CONCLUSION: SLN and NLC formulations of LE can be stated among the systems that can be an alternative to conventional systems with fewer side-effects in the treatment of inflammatory problems.

Influence of Vehicles and Penetration Enhancers on the Permeation of Cinnarizine Through the Skin

Objectives: The aim of this study was to determine the influence of vehicles and penetration enhancers on the penetration and permeation of cinnarizine (CNZ) through the skin. Materials and Methods: Topical formulations based on hydrogel, o/w emulsion and oleaginous cream were prepared. After determination of physical properties of formulations, the penetration and permeation of CNZ through the stratum corneum and full-thickness skin was investigated by an ex vivo study. Results: The cumulative amount of CNZ permeated from the base hydrogel formulation was about 5 times higher than the base o/w emulsion and base oleaginous cream formulations. The incorporation of penetration enhancers to the base hydrogel and o/w emulsion formulations generally increased CNZ penetration through the skin. Transcutol® was confirmed to provide the highest penetration in the hydrogel formulation. Propylene glycol was found to be the most suitable penetration enhancer for CNZ in the oleaginous cream. Glycerol and oleic acid displayed the highest effect in the o/w emulsion. Conclusion: It was concluded that the hydrogel containing Transcutol® provided the highest penetration through the skin among all formulations and this formulation could be an alternative to the oral route in the treatment of Ménière's disease and motion sickness. Thus, the risk of systemic side effects caused by oral medication can be reduced or eliminated.

Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies

To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière's disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated

Design of colloidal drug carriers of celecoxib for use in treatment of breast cancer and leukemia.

Inflammation develops initiation and pathological process of cancer. Nanoscale drug carriers are required to be investigated for delivery of actives at cellular level for treatment of various cancer types. Solid lipid nanoparticles (CLX-SLN), nanostructured lipid carriers (CLX-NLC) and a nanoemulsion (CLX-NE) of celecoxib (CLX), a selective cyclooxygenase-2 inhibitor, were formulated for use in remedy of breast cancer and acute promyelocytic leukemia. The hot high pressure homogenization technique was employed to product formulations. Scanning electron micrographs were utilized for morphological characterization of formulations. Laser diffraction (LD), photon correlation spectroscopy (PCS) and differential scanning calorimetry (DSC) were used for examination of their physical stability by storing them at various temperatures. Drug release profiles of formulations were obtained. Their activity on cancer cells was investigated in the cell culture experiments. Stable formulations having homogenous size distribution were obtained below 200 nm with high drug payloads between 93.76% and 96.66%. Nanoparticles were ascertained to contribute controlled drug release. CLX-SLN induced the highest decrease in numbers of human breast cancer and human acute promyelocytic leukemia cells through the activation of the cell death cascades especially apoptosis in comparison to CLX-NLC, CLX-NE and the pure CLX application (p < 0.05). Nanoformulations of CLX optimized in this study were found to have various advantages expected from sophisticated drug delivery systems in order to achieve higher CLX efficiency at cellular level. Thus, they are able to be administered efficaciously alone and in combination therapies in remedy of breast cancer and acute promyelocytic leukemia.

Therapeutic potential of drug delivery by means of lipid nanoparticles: reality or illusion?

BACKGROUND: Solid lipid nanoparticles (SLN) are colloidal drug carrier systems that contribute several properties required from a sophisticated drug delivery system for increasing drug bioavailability and providing effective therapy. Many advantages of SLN have been reported over traditional dosage forms and their colloidal counterparts in the studies since the early 1990s. They were optimized for oral drug delivery for the first time. The first SLN formulations were produced by reducing the particle size of solid lipid microparticles by spray congealing technique in the late 1980s. Then, studies have been continued investigating for their different administration routes else including parenteral, transdermal, ocular, nasal, respiratory etc. METHODS: Their foremost qualifications such as their biocompatible nature and high drug entrapment efficiency make them promising colloidal drug carrier systems for the effective treatment of serious disasters like genetic disorders and cancer. CONCLUSION: In this review, therapeutic potential of drug delivery of SLN and nanostructured lipid carriers (NLC, the second generation of SLN) are summarized considering researches and patents on their administration via different routes and their preparations in the pharmaceutical market.

Optimization of piribedil mucoadhesive tablets for efficient therapy of Parkinson's disease: physical characterization and ex vivo drug permeation through buccal mucosa.

OBJECTIVE: The aim of this study was optimization of buccal piribedil (PR) mucoadhesive tablets to improve its low bioavailability and provide controlled release for the treatment of Parkinson's disease. METHODS: Buccal tablets were prepared by direct compression method using carbomer (CP), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Physical properties of powder mixtures and buccal tablets were evaluated. Physicochemical compatibility between ingredients was investigated with infrared spectroscopy and differential scanning calorimetry analysis. In vitro dissolution profiles and drug release kinetics of buccal tablets were investigated. Mucoadhesion and ex vivo permeation studies were performed using sheep buccal mucosa. RESULTS: Powder mixtures demonstrated sufficient flow properties and physical characteristics of all tablet formulations were within compendia limits. Tablet ingredients were absent of any chemical interactions. CP tablets displayed slower drug release compared to HPMC tablets with zero order release, while CMC tablets lost their integrity and released entire drug after 6 h following Higuchi model. All formulations displayed adequate mucoadhesion and steady state flux of PR through buccal mucosa were higher with HPMC compared to CP-containing tablets. CONCLUSION: Overall, HPMC was found to combine desired controlled release and mucoadhesion characteristics with sufficient pharmaceutical quality for optimization of buccal tablets. Piribedil mucoadhesive buccal tablets designed for the first time may introduce a new alternative for the treatment of Parkinson's disease.

Formulation and characterization of solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsion of lornoxicam for transdermal delivery.

Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsion (NE) of lornoxicam (LRX) were prepared for the treatment of painful and inflammatory conditions of the skin. Compritol® 888 ATO, Lanette® O and oleic acid were used as solid and liquid lipids. SLN, NLC and NE were found physically stable at various temperatures for 6 months. Case I diffusional drug release was detected as the dominant mechanism indicating Fickian drug diffusion from nanoparticles and nanoemulsion. The highest rate of drug penetration through rat skin was obtained with NE followed by NLC, SLN and a gel formulation. Nanoformulations significantly increased drug penetration through rat skin compared to the gel (p<0.05). Thus, SLN, NLC and NE of LRX can be suggested for relieving painful and inflammatory conditions of the skin.