Preliminary safety and in vivo efficacy of Acmella oleracea extract-loaded glycolipid emulsion serum-Effects on ocular irritation, dermal absorption, and facial skin biophysical and microrelief properties.

Objective: Substantial efforts have been progressively devoted to developing innovative, safe, and effective topical anti-aging products that not only improve the appearance of aged skin but also prioritize environmental sustainability and the responsible use of natural resources. Thus, the current study targeted to evaluate novel, natural emulsion/serum comprising new glycolipid emulsifier (lauryl glucoside/myristyl glucoside/polyglyceryl-6 laurate) and Acmella oleracea plant extract as a model active.

Methods: The developed serum was assessed concerning its stability (freeze-thaw test, accelerated study), safety (in vitro screening of eye irritation potential, dermal absorption study) and efficacy (randomized, active/reference-controlled, half-face, in vivo study).

Efficient Development of Green Emulsifier/Emollient-Based Emulsion Vehicles: From RSM Optimal Experimental Design to Abridged In Vivo Assessment.

Since natural-origin, sustainable ingredients are preferred by modern consumers, novel emulsifiers and emollients keep entering the market. This study hypothesizes that a combination of in silico, instrumental tools and simplified sensory studies could be used to efficiently characterize emulsions in a shorter timeframe. A total of 22 rather simple o/w emulsions were prepared by a time/energy-saving emulsification process.

Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation.

Contemporary trends in combinatorial chemistry and the design of pharmaceuticals targeting brain disorders have favored the development of drug candidates with increased lipophilicity and poorer water solubility, with the expected improvement in delivery across the blood-brain barrier (BBB). The growing availability of innovative excipients/ligands allowing improved brain targeting and controlled drug release makes the lipid nanocarriers a reasonable choice to overcome the factors impeding drug delivery through the BBB. However, a wide variety of methods, study designs and experimental conditions utilized in the literature hinder their systematic comparison, and thus slows the advances in brain-targeting by lipid-based nanoparticles.

Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study.

Hypothesis: Lipophilic cannabidiol can be solubilized in oil-in water nanoemulsions, which can then be impregnated into chitosan hydrogels forming another colloidal system that will facilitate cannabidiol's release. The delivery from both systems was compared, alongside structural and biological studies, to clarify the effect of the two carriers' structure on the release and toxicity of the systems.

Experiments: Oil-in-water nanoemulsions (NEs) and the respective nanoemulsion-filled chitosan hydrogels (NE/HGs) were formulated as carriers of cannabidiol (CBD).

Topically applied lipid-containing emulsions based on PEGylated emulsifiers: Formulation, characterization, and evaluation of their impact on skin properties ex vivo and in vivo.

PEGylated emulsifiers have been largely used in topical formulations for skin research. They have been a continuous study focus in our group as well. According to our previous studies, severe interruptions of the skin barrier were observed with certain types of emulsifiers.

Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study.

Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization challenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems.

Simultaneous Physico-Mechanical and In Vivo Assessment towards Factual Skin Performance Profile of Topical Polymeric Film-Forming Systems.

Topical film-forming systems (FFS) change drastically after solvent displacement, therefore indicating their skin metamorphosis/transformation as a property of special regulatory and research interest. This paper deals with the lack of suitable characterization techniques, suggesting a set of methods able to provide a comprehensive notion of FFS skin performance. After screening the physico-chemical, mechanical and sensory properties of FFS and resulting films, an elaborate three-phase in vivo study was performed, covering skin irritation, friction and substantivity.

'All-natural' anti-wrinkle emulsion serum with Acmella oleracea extract: A design of experiments (DoE) formulation approach, rheology and in vivo skin performance/efficacy evaluation.

Objective: The growing consumers' preferences and concerns regarding healthy ageing, youthful skin appearance, environmental protection and sustainability have triggered an ever-increasing trend towards natural, eco-friendly and ethically sourced anti-ageing products. Accordingly, this paper describes design and evaluation of novel, safe, effective and high-quality emulsion serums, completely based on ingredients of natural origin, intended for improving facial fine lines and wrinkles.

Methods: Model formulations, stabilized by an innovative glycolipid mixed emulsifier (lauryl glucoside/myristyl glucoside/polyglyceryl-6 laurate) and containing Acmella oleracea extract as a model anti-ageing active, were prepared by cold process and fully assessed regarding their rheological behaviour (continuous rotational and oscillatory tests) and physical stability (dynamic-mechanical thermoanalysis - DMTA test).

Comparative efficacy evaluation of different penetration enhancement strategies for dermal delivery of poorly soluble drugs - A case with sertaconazole nitrate.

The aim of this study was to compare the efficacy of different approaches for enhancement of dermal availability of the highly lipophilic antifungal model drug - sertaconazole nitrate (SN). For this purpose, a physical penetration enhancer - dissolving microneedles (MNs) was fabricated by filling moulds with liquid formulation based on polyvinylpyrrolidone and loaded with SN. Dissolving MNs were characterised regarding their morphological and mechanical characteristics.

The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence.

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment.

Biological Evaluation of Oil-in-Water Microemulsions as Carriers of Benzothiophene Analogues for Dermal Applications.

During the last decade, many studies have been reported on the design and formulation of novel drug delivery systems proposed for dermal or transdermal administration. The efforts focus on the development of biocompatible nanodispersions that can be delivered to the skin and treat severe skin disorders, including cancer. In this context, oil-in-water (O/W) microemulsions have been developed to encapsulate and deliver lipophilic bioactive molecules for dermal application.

Technological Approaches for Improving Vaccination Compliance and Coverage.

Vaccination has been well recognised as a critically important tool in preventing infectious disease, yet incomplete immunisation coverage remains a major obstacle to achieving disease control and eradication. As medical products for global access, vaccines need to be safe, effective and inexpensive. In line with these goals, continuous improvements of vaccine delivery strategies are necessary to achieve the full potential of immunisation.

Tacrolimus-loaded lecithin-based nanostructured lipid carrier and nanoemulsion with propylene glycol monocaprylate as a liquid lipid: Formulation characterization and assessment of dermal delivery compared to referent ointment.

Nanostructured lipid carriers (NLC) and nanoemulsions (NE) are colloid carriers which could improve dermal delivery of tacrolimus. The aims of this study were to evaluate effects of different formulation and process parameters on physicochemical characteristics and stability of lecithin-based NLC with glyceryl palmitostearate as solid and propylene glycol monocaprylate as liquid lipid and to compare the influence of different inner structure of tacrolimus-loaded NLC and corresponding NE on physicochemical characteristics, stability, entrapment efficiency, in vitro drug release and overall skin performance. Solid/liquid lipid ratio, total amount of lipids, homogenization pressure and cooling after the preparation were identified as critical variables in NLC development.

Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies.

This study aimed to investigate the potential of lecithin-based nanoemulsions costabilized by sucrose esters, with and without skin pretreatment with stainless steel microneedles, to improve delivery of aceclofenac, as a model drug, into/across the skin. The characterization revealed favorable droplet size (about 180 nm), narrow size distribution (<0.15), high surface charge (about -40 mV) and satisfying long-term stability (one year at 4 ± 1 °C) of the formulation costabilized by sucrose palmitate, demonstrating a similar trend observed for the reference stabilized by widely used lecithin/polysorbate 80 combination.

Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance.

Two types of biocompatible surfactants were evaluated for their capability to formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly water-soluble model drugs differing in properties and concentrations: alkyl polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated surfactants (glycereth-7-caprylate/ caprate and polysorbate 80). Phase behavior, structural inversion and microemulsion solubilization potential for sertaconazole nitrate and adapalene were found to be highly dependent on the surfactants structure and HLB value. Performed characterization (polarized light microscopy, pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a formulation containing glycereth- 7-caprylate/caprate as suitable for incorporation of both drugs, whereas alkyl polyglucoside-based systems did not exhibit satisfying solubilization capacity for sertaconazole nitrate.

Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances.

In order to improve skin penetration of tacrolimus we aimed to develop potentially non-irritant, lecithin-based microemulsions containing ethanol, isopropanol and/or propylene glycol as cosurfactants, varying caprylic/capric triglycerides and propylene glycol monocaprylate as oil phase. The influence of excipients on the size of microemulsion region in pseudo-ternary phase diagrams and their ability to form different types of microemulsions was evaluated. The comprehensive physicochemical characterization of microemulsions and the evaluation of their structure was performed, while the localization of tacrolimus in microemulsions was further investigated using electron paramagnetic resonance spectroscopy.

Critical quality attributes, in vitro release and correlated in vitro skin permeation-in vivo tape stripping collective data for demonstrating therapeutic (non)equivalence of topical semisolids: A case study of "ready-to-use" vehicles.

This work aimed to prove the ability of "ready-to-use" topical vehicles based on alkyl polyglucoside-mixed emulsifier (with/without co-solvent modifications) to replace the conventionally used pharmacopoeial bases (e.g., non-ionic hydrophilic cream) in compounding practice.

Parenteral nanoemulsions of risperidone for enhanced brain delivery in acute psychosis: Physicochemical and in vivo performances.

This work aimed to deepen the lately acquired knowledge about parenteral nanoemulsions as carriers for brain delivery of risperidone, a poorly water-soluble antipsychotic drug, through establishing the prospective relationship between their physicochemical, pharmacokinetic, biodistribution, and behavioral performances. For this purpose, two optimized risperidone-loaded nanoemulsions, stabilized by lecithin or lecithin/polysorbate 80 mixture, and costabilized by sodium oleate, were produced by high-pressure homogenization. The characterization revealed the favorable droplet size, narrow size distribution, high surface charge, with proven stability to autoclaving and long-term stability for at least one year at 25±2°C.

Changes in bacterial resistance patterns in children with urinary tract infections on antimicrobial prophylaxis at University Hospital in Split.

Background: We assessed prevalence and resistance of uropathogens on antimicrobial agents (AA) from urine cultures (UC) in children hospitalized with urinary tract infections (UTI) at University Hospital in Split.

Material/methods: During the 7-year period, children hospitalized only once with UTI alone were compared to those repeatedly hospitalized, and who received long-term antimicrobial prophylaxis (LTAP), as well as those with associated anomalies of the urinary system (US).

Results: E.

Autoantibodies in patients treated for active pulmonary tuberculosis.

The genesis of auto-immune antibodies directed against the own tissue antigens of a host may be due to the host's immune response to mycobacteria. The prospective study included 110 patients treated for active pulmonary tuberculosis and the control group of 60 healthy subjects, volontary blood donors. Applying the method of indirect immnunofluorescence and cryostat sections of rat organs and human larynx cancer epithelial cell line (HEp-2 cells), the prescence of the following autoantibodies in the serum of the examined patients was examined: anti,nclear (ANA), anticardiac (ACA), antimitochondrial (AMA), antiparietal (APA), anti smooth muscular (ASMA), antithyroidal (ATA), rheumnatoid factor (RF).