Receptor Pharmacogenomics: Deciphering Genetic Influence on Drug Response.

The paradigm "one drug fits all" or "one dose fits all" will soon be challenged by pharmacogenetics research and application. Drug response-efficacy or safety-depends on interindividual variability. The current clinical practice does not include genetic screening as a routine procedure and does not account for genetic variation. Patients with the same illness receive the same treatment, yielding different responses. Integrating pharmacogenomics in therapy would provide critical information about how a patient will respond to a certain drug. Worldwide, great efforts are being made to achieve a personalized therapy-based approach. Nevertheless, a global harmonized guideline is still needed. Plasma membrane proteins, like receptor tyrosine kinase (RTK) and G protein-coupled receptors (GPCRs), are ubiquitously expressed, being involved in a diverse array of physiopathological processes. Over 30% of drugs approved by the FDA target GPCRs, reflecting the importance of assessing the genetic variability among individuals who are treated with these drugs. Pharmacogenomics of transmembrane protein receptors is a dynamic field with profound implications for precision medicine. Understanding genetic variations in these receptors provides a framework for optimizing drug therapies, minimizing adverse reactions, and advancing the paradigm of personalized healthcare.

Novel Collagen Membrane Formulations with Irinotecan or Minocycline for Potential Application in Brain Cancer.

Our study explores the development of collagen membranes with integrated minocycline or irinotecan, targeting applications in tissue engineering and drug delivery systems. Type I collagen, extracted from bovine skin using advanced fibril-forming technology, was crosslinked with glutaraldehyde to create membranes. These membranes incorporated minocycline, an antibiotic, or irinotecan, a chemotherapeutic agent, in various concentrations. The membranes, varying in drug concentration, were studied by water absorption and enzymatic degradation tests, demonstrating a degree of permeability. We emphasize the advantages of local drug delivery for treating high-grade gliomas, highlighting the targeted approach's efficacy in reducing systemic adverse effects and enhancing drug bioavailability at the tumor site. The utilization of collagen membranes is proposed as a viable method for local drug delivery. Irinotecan's mechanism, a topoisomerase I inhibitor, and minocycline's broad antibacterial spectrum and inhibition of glial cell-induced membrane degradation are discussed. We critically examine the challenges posed by the systemic administration of chemotherapeutic agents, mainly due to the blood-brain barrier's restrictive nature, advocating for local delivery methods as a more effective alternative for glioblastoma treatment. These local delivery strategies, including collagen membranes, are posited as significant advancements in enhancing therapeutic outcomes for glioblastoma patients.

Development and Evaluation of Docetaxel-Loaded Nanostructured Lipid Carriers for Skin Cancer Therapy.

This study focuses on the design, characterization, and optimization of nanostructured lipid carriers (NLCs) loaded with docetaxel for the treatment of skin cancer. Employing a systematic formulation development process guided by Design of Experiments (DoE) principles, key parameters such as particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were optimized to ensure the stability and drug-loading efficacy of the NLCs. Combined XRD and cryo-TEM analysis were employed for NLC nanostructure evaluation, confirming the formation of well-defined nanostructures. In vitro kinetics studies demonstrated controlled and sustained docetaxel release over 48 h, emphasizing the potential for prolonged therapeutic effects. Cytotoxicity assays on human umbilical vein endothelial cells (HUVEC) and SK-MEL-24 melanoma cell line revealed enhanced efficacy against cancer cells, with significant selective cytotoxicity and minimal impact on normal cells. This multidimensional approach, encompassing formulation optimization and comprehensive characterization, positions the docetaxel-loaded NLCs as promising candidates for advanced skin cancer therapy. The findings underscore the potential translational impact of these nanocarriers, paving the way for future preclinical investigations and clinical applications in skin cancer treatment.

Application of Common Culinary Herbs for the Development of Bioactive Materials.

Hyssop (Hyssopus officinalis L.) and oregano (Origanum vulgare L.), traditionally used for their antimicrobial properties, can be considered viable candidates for nanotechnology applications, in particular for the phytosynthesis of metal nanoparticles. The present work aims to evaluate the potential application of hyssop and oregano for the phytosynthesis of silver nanoparticles, as well as to evaluate the biological activities of their extracts and obtained nanoparticles (antioxidant potential, as well as cell viability, inflammation level and cytotoxicity in human fibroblasts HFIB-G cell line studies). In order to obtain natural extracts, two extraction methods were applied (classical temperature extraction and microwave-assisted extraction), with the extraction method having a major influence on their composition, as demonstrated by both the total phenolic compounds (significantly higher for the microwave-assisted extraction; the oregano extracts had consistently higher TPC values, compared with the hyssop extracts) and in terms of individual components identified via HPLC. The obtained nanoparticles ware characterized via X-ray diffraction (XRD) and transmission electron microscopy (TEM), with the lowest dimension nanoparticles being recorded for the nanoparticles obtained using the oregano microwave extract (crystallite size 2.94 nm through XRD, average diameter 10 nm via TEM). The extract composition and particle size also influenced the antioxidant properties (over 60% DPPH inhibition being recorded for the NPs obtained using the oregano microwave extract). Cell viability was not affected at the lowest tested concentrations, which can be correlated with the nitric oxide level. Cell membrane integrity was not affected after exposure to classic temperature hyssop extract-NPs, while the other samples led to a significant LDH increase.

Development and Characterization of New Miconazole-Based Microemulsions for Buccal Delivery by Implementing a Full Factorial Design Modeling.

This research aimed to develop miconazole-based microemulsions using oleic acid as a natural lipophilic phase and a stabilizer mixture comprising Tween 20 and PEG 400 to solubilize miconazole as an antifungal agent known for its activity in oral candidiasis and to improve its bioavailability. The formulation and preparation process was combined with a mathematical approach using a 23-full factorial plan. Fluid and gel-like microemulsions were obtained and analyzed considering pH, conductivity, and refractive index, followed by extensive analyses focused on droplet size, zeta potential, rheological behavior, and goniometry. In vitro release tests were performed to assess their biopharmaceutical characteristics. Independent variables coded X1-Oleic acid (%, w/w), X2-Tween 20 (%, w/w), and X3-PEG 400 (%, w/w) were analyzed in relationship with three main outputs like mean droplet size, work of adhesion, and diffusion coefficient by combining statistical tools with response surface methodology. The microemulsion containing miconazole base-2%, oleic acid-5%, Tween 20-40%, PEG 400-20%, and water-33% exhibited a mean droplet size of 119.6 nm, a work of adhesion of 71.98 mN/m, a diffusion coefficient of 2.11·10-5 cm2/s, and together with remarked attributes of two gel-like systems formulated with higher oil concentrations, modeled the final optimization step of microemulsions as potential systems for buccal delivery.

Pyrethrins and Pyrethroids: A Comprehensive Review of Natural Occurring Compounds and Their Synthetic Derivatives.

This comprehensive scientific review provides an in-depth analysis of both the natural compounds, pyrethrins, and their synthetic derivatives, pyrethroids, focusing on their classification, biosynthesis, mechanism of action, general and pharmaceutical uses, as well as their toxicity and environmental impact. Pyrethrins, derived from certain plant species, have long been recognized for their potent insecticidal properties. The review begins by examining the classification of pyrethrins and pyrethroids, elucidating their structural characteristics and unique features within the field of natural and synthetic compounds. The biosynthetic pathways responsible for producing pyrethrins in plants are discussed, highlighting the enzymatic reactions and genetic regulation involved. In addition, the synthesis of pyrethroid derivatives is explored, including both natural and synthetic sources and potential optimization strategies. Understanding the mechanisms of action by which pyrethrins and pyrethroids exert their insecticidal effects is a crucial aspect of this review. Complex interactions with the nervous systems of target organisms are examined, providing insights into their selective toxicity and modes of action. In addition, the various applications of these compounds are explored, from their use in agriculture for pest control to their incorporation into household insecticides and potential pharmaceutical applications. The review also critically evaluates the potential toxicity of pyrethrins and pyrethroids to human health. By consolidating current knowledge and research findings, this review provides a comprehensive understanding of the properties and applications of pyrethrins and pyrethroids, highlighting their benefits and risks, and the importance of responsible and sustainable use in various areas.

Chitosan Biomaterials: Advances and Challenges.

The purpose of this Special Issue was to review research focusing on the development of formulations based on chitosan or its derivatives together with other molecules, producing biomaterials with improved physicochemical properties and effects [...].

Molecular Mapping of Antifungal Mechanisms Accessing Biomaterials and New Agents to Target Oral Candidiasis.

Oral candidiasis has a high rate of development, especially in immunocompromised patients. Immunosuppressive and cytotoxic therapies in hospitalized HIV and cancer patients are known to induce the poor management of adverse reactions, where local and systemic candidiasis become highly resistant to conventional antifungal therapy. The development of oral candidiasis is triggered by several mechanisms that determine oral epithelium imbalances, resulting in poor local defense and a delayed immune system response. As a result, pathogenic fungi colonies disseminate and form resistant biofilms, promoting serious challenges in initiating a proper therapeutic protocol. Hence, this study of the literature aimed to discuss possibilities and new trends through antifungal therapy for buccal drug administration. A large number of studies explored the antifungal activity of new agents or synergic components that may enhance the effect of classic drugs. It was of significant interest to find connections between smart biomaterials and their activity, to find molecular responses and mechanisms that can conquer the multidrug resistance of fungi strains, and to transpose them into a molecular map. Overall, attention is focused on the nanocolloids domain, nanoparticles, nanocomposite synthesis, and the design of polymeric platforms to satisfy sustained antifungal activity and high biocompatibility with the oral mucosa.

Bacterial Cellulose-A Remarkable Polymer as a Source for Biomaterials Tailoring.

Nowadays, the development of new eco-friendly and biocompatible materials using 'green' technologies represents a significant challenge for the biomedical and pharmaceutical fields to reduce the destructive actions of scientific research on the human body and the environment. Thus, bacterial cellulose (BC) has a central place among these novel tailored biomaterials. BC is a non-pathogenic bacteria-produced polysaccharide with a 3D nanofibrous structure, chemically identical to plant cellulose, but exhibiting greater purity and crystallinity. Bacterial cellulose possesses excellent physicochemical and mechanical properties, adequate capacity to absorb a large quantity of water, non-toxicity, chemical inertness, biocompatibility, biodegradability, proper capacity to form films and to stabilize emulsions, high porosity, and a large surface area. Due to its suitable characteristics, this ecological material can combine with multiple polymers and diverse bioactive agents to develop new materials and composites. Bacterial cellulose alone, and with its mixtures, exhibits numerous applications, including in the food and electronic industries and in the biotechnological and biomedical areas (such as in wound dressing, tissue engineering, dental implants, drug delivery systems, and cell culture). This review presents an overview of the main properties and uses of bacterial cellulose and the latest promising future applications, such as in biological diagnosis, biosensors, personalized regenerative medicine, and nerve and ocular tissue engineering.

Insights from a Box-Behnken Optimization Study of Microemulsions with Salicylic Acid for Acne Therapy.

The present study brings to attention a method to develop salicylic acid-based oil in water (O/W) microemulsions using a tensioactive system based on Tween 80, lecithin, and propylene glycol (PG), enriched with a vegetable oat oil phase and hyaluronic acid. The systems were physically characterized and the Quality by design approach was applied to optimize the attributes of microemulsions using Box-Behnken modeling, combined with response surface methodology. For this purpose, a 33 fractional factorial design was selected. The effect of independent variables namely X1: Tween 80/PG (%), X2: Lecithin (%), X3: Oil phase (%) was analyzed considering their impact upon the internal structure and evaluated parameters chosen as dependent factors: viscosity, mean droplet size, and work of adhesion. A high viscosity, a low droplet size, an adequate wettability-with a reduced mechanical work-and clarity were considered as desirable for the optimal systems. It was found that the optimal microemulsion which complied with the established conditions was based on: Tween 80/PG 40%, lecithin 0.3%, oat oil 2%, salicylic acid 0.5%, hyaluronic acid 1%, and water 56.2%. The response surface methodology was considered an appropriate tool to explain the impact of formulation factors on the physical properties of microemulsions, offering a complex pattern in the assessment of stability and quality attributes for the optimized formulation.

An Overview Regarding Microbial Aspects of Production and Applications of Bacterial Cellulose.

Cellulose is the most widely used biopolymer, accounting for about 1.5 trillion tons of annual production on Earth. Bacterial cellulose (BC) is a form produced by different species of bacteria, representing a purified form of cellulose. The structure of bacterial cellulose consists of glucose monomers that give it excellent properties for different medical applications (unique nanostructure, high water holding capacity, high degree of polymerization, high mechanical strength, and high crystallinity). These properties differ depending on the cellulose-producing bacteria. The most discussed topic is related to the use of bacterial cellulose as a versatile biopolymer for wound dressing applications. The aim of this review is to present the microbial aspects of BC production and potential applications in development of value-added products, especially for biomedical applications.

3D Porous Collagen Matrices-A Reservoir for In Vitro Simultaneous Release of Tannic Acid and Chlorhexidine.

The treatment of wounds occurring accidentally or as a result of chronic diseases most frequently requires the use of appropriate dressings, mainly to ensure tissue regeneration/healing, at the same time as treating or preventing potential bacterial infections or superinfections. Collagen type I-based scaffolds in tandem with adequate antimicrobials can successfully fulfill these requirements. In this work, starting from the corresponding hydrogels, we prepared a series of freeze-dried atelocollagen type I-based matrices loaded with tannic acid (TA) and chlorhexidine digluconate (CHDG) as active agents with a broad spectrum of antimicrobial activity and also as crosslinkers for the collagen network. The primary aim of this study was to design an original and reliable algorithm to in vitro monitor and kinetically analyze the simultaneous release of TA and CHDG from the porous matrices into an aqueous solution of phosphate-buffered saline (PBS, pH 7.4, 37 °C) containing micellar carriers of a cationic surfactant (hexadecyltrimethylammonium bromide, HTAB) as a release environment that roughly mimics human extracellular fluids in living tissues. Around this central idea, a comprehensive investigation of the lyophilized matrices (morpho-structural characterization through FT-IR spectroscopy, scanning electron microscopy, swelling behavior, resistance against the collagenolytic action of collagenase type I) was carried out. The kinetic treatment of the release data displayed a preponderance of non-Fickian-Case II diffusion behavior, which led to a general anomalous transport mechanism for both TA and CHDG, irrespective of their concentrations. This is equivalent to saying that the release regime is not governed only by the gradient concentration of the releasing components inside and outside the matrix (like in ideal Fickian diffusion), but also, to a large extent, by the relaxation phenomena of the collagen network (determined, in turn, by its crosslinking degree induced by TA and CHDG) and the dynamic capacity of the HTAB micelles to solubilize the two antimicrobials. By controlling the degree of physical crosslinking of collagen with a proper content of TA and CHDG loaded in the matrix, a tunable, sustainable release profile can be obtained.

An Overview of Cellulose Derivatives-Based Dressings for Wound-Healing Management.

Presently, notwithstanding the progress regarding wound-healing management, the treatment of the majority of skin lesions still represents a serious challenge for biomedical and pharmaceutical industries. Thus, the attention of the researchers has turned to the development of novel materials based on cellulose derivatives. Cellulose derivatives are semi-synthetic biopolymers, which exhibit high solubility in water and represent an advantageous alternative to water-insoluble cellulose. These biopolymers possess excellent properties, such as biocompatibility, biodegradability, sustainability, non-toxicity, non-immunogenicity, thermo-gelling behavior, mechanical strength, abundance, low costs, antibacterial effect, and high hydrophilicity. They have an efficient ability to absorb and retain a large quantity of wound exudates in the interstitial sites of their networks and can maintain optimal local moisture. Cellulose derivatives also represent a proper scaffold to incorporate various bioactive agents with beneficial therapeutic effects on skin tissue restoration. Due to these suitable and versatile characteristics, cellulose derivatives are attractive and captivating materials for wound-healing applications. This review presents an extensive overview of recent research regarding promising cellulose derivatives-based materials for the development of multiple biomedical and pharmaceutical applications, such as wound dressings, drug delivery devices, and tissue engineering.

Foray into Concepts of Design and Evaluation of Microemulsions as a Modern Approach for Topical Applications in Acne Pathology.

With a fascinating complexity, governed by multiple physiological processes, the skin is considered a mantle with protective functions which during lifetime are frequently impaired, triggering dermatologic disorders. As one of the most prevalent dermatologic conditions worldwide, characterized by a complex pathogenesis and a high recurrence, acne can affect the patient's quality of life. Smart topical vehicles represent a good option in the treatment of a versatile skin condition. By surpassing the stratum corneum known for diffusional resistance, a superior topical bioavailability can be obtained at the affected place. In this direction, the literature study presents microemulsions as a part of a condensed group of modern formulations. Microemulsions are appreciated for their superior profile in matters of drug delivery, especially for challenging substances with hydrophilic or lipophilic structures. Formulated as transparent and thermodynamically stable systems, using simplified methods of preparation, microemulsions have a simple and clear appearance. Their unique structures can be explained as a function of the formulation parameters which were found to be the mainstay of a targeted therapy.

Ciprofloxacin-Collagen-Based Materials with Potential Oral Surgical Applications.

We report in this paper the synthesis and characterization of a new collagen-based material. This material was obtained in a spongy form and was functionalized with an antibiotic, ciprofloxacin. The targeted applications of these kind of materials concern the post-operative prophylaxis. The in vitro tests (antimicrobial, cytotoxic, drug release) showed that sponges with a concentration of 0.75 g of ciprofloxacin per gram of collagen could be beneficial for the desired applications.

New Opportunity to Formulate Intranasal Vaccines and Drug Delivery Systems Based on Chitosan.

In an attempt to develop drug delivery systems that bypass the blood-brain barrier (BBB) and prevent liver and intestinal degradation, it was concluded that nasal medication meets these criteria and can be used for drugs that have these drawbacks. The aim of this review is to present the influence of the properties of chitosan and its derivatives (mucoadhesion, permeability enhancement, surface tension, and zeta potential) on the development of suitable nasal drug delivery systems and on the nasal bioavailability of various active pharmaceutical ingredients. Interactions between chitosan and proteins, lipids, antigens, and other molecules lead to complexes that have their own applications or to changing characteristics of the substances involved in the bond (conformational changes, increased stability or solubility, etc.). Chitosan and its derivatives have their own actions (antibacterial, antifungal, immunostimulant, antioxidant, etc.) and can be used as such or in combination with other molecules from the same class to achieve a synergistic effect. The applicability of the properties is set out in the second part of the paper, where nasal formulations based on chitosan are described (vaccines, hydrogels, nanoparticles, nanostructured lipid carriers (NLC), powders, emulsions, etc.).

Selection of Optimal Operating Conditions for Extraction of Myrtus Communis L. Essential Oil by the Steam Distillation Method.

Myrtus communis L. is one of the important aromatic and medicinal species from the Mediterranean area. It is used in various fields such as culinary, cosmetic, pharmaceutical, therapeutic, and industrial applications. Thus, a Box-Wilson experimental plan was used in this study to select the optimal operating conditions in order to obtain high volumes of essential oils. The factorial design method was applied to evaluate at an industrial scale the effect of major process variables on the essential oil extraction from Myrtus communis L. herbs by the steam distillation method. The input variables considered as significant operating conditions were: X1-boiler occupancy rate (boilers were filled to 50%, 75%, and 100%), X2-distillation duration (distillation was continued 60, 75, and 90 min), and X3-particle size (herbs were cut in sizes of 10, 20, and 30 mm via guillotine). The dependent variable selected, coded as Y, was the essential oil volume obtained (mL). The steps of the classical statistical experimental design technique were complemented with the Taguchi method to improve the extraction efficacy of essential oil from Myrtus communis L., and the optimum parameter conditions were selected: boiler occupancy rate 100%, distillation duration 75 min, and particle size 20 mm. Following the optimum parameters, the GC-MS assay revealed for the Myrtus communis L. essential oil two predominant components, α-pinene-33.14% and eucalyptol-55.09%.

Oxytetracycline versus Doxycycline Collagen Sponges Designed as Potential Carrier Supports in Biomedical Applications.

Many research studies are directed toward developing safe and efficient collagen-based biomaterials as carriers for drug delivery systems. This article presents a comparative study of the properties of new collagen sponges prepared and characterized by different methods intended for biomedical applications. The structural integrity is one of the main properties for a biomaterial in order for it to be easily removed from the treated area. Thus, the effect of combining a natural polymer such as collagen with an antimicrobial drug such as oxytetracycline or doxycycline and glutaraldehyde as the chemical cross-linking agent influences the cross-linking degree of the material, which is in direct relation to its resistance to collagenase digestion, the drug kinetic release profile, and in vitro biocompatibility. The enzymatic degradation results identified oxytetracycline as the best inhibitor of collagenase when the collagen sponge was cross-linked with 0.5% glutaraldehyde. The drug release kinetics revealed an extended release of the antibiotic for oxytetracycline-loaded collagen sponges compared with doxycycline-loaded collagen sponges. Considering the behavior of differently prepared sponges, the collagen sponge with oxytetracycline and 0.5% glutaraldehyde could represent a viable polymeric support for the prevention/treatment of infections at the application site, favoring tissue regeneration.

Efficiency of Multiparticulate Delivery Systems Loaded with Flufenamic Acid Designed for Burn Wound Healing Applications.

Burns are soft tissue injuries that require particular care for wound healing. Current tissue engineering approaches are aimed at identifying the most efficient treatment combinations to restore the tissue properties and function by using adapted scaffolds or delivery platforms for tissue repair and regeneration by triggering molecules. To reduce the inflammation associated with skin burns, the addition of an anti-inflammatory factor in these scaffolds would greatly increase the quality of the therapy. Therefore, this study is aimed at obtaining and validating a novel multiparticulate system based on a collagen matrix with controlled delivery of flufenamic acid anti-inflammatory drug for burn wound healing applications. In this work, we have characterized the properties and biocompatibility of these multiparticulate drug delivery systems (MDDS) and we have demonstrated their efficiency against burns and soft tissue lesions, particularly when the drug was microencapsulated, and thus with a controlled release. This study contributes to the advancement in therapy of burns and burn wound healing applications.

Collagen-Polyvinyl Alcohol-Indomethacin Biohybrid Matrices as Wound Dressings.

The aim of this study is to design, develop and evaluate new biohybrid sponges based on polymers (collagen and polyvinyl alcohol) with and without indomethacin as anti-inflammatory drug model to be used for tissue regeneration in wound healing. Type I fibrillar collagen in the form of a gel and different concentrations of polyvinyl alcohol were mixed together to prepare composite gels. Both control samples, without indomethacin and with indomethacin, were obtained. All samples were crosslinked with glutaraldehyde. By freeze-drying of hydrogels, the spongious forms (matrices) were obtained. The matrices were characterized by FT-IR spectroscopy, scanning electron microscopy (SEM), water absorption, enzymatic degradation and in vitro indomethacin release. The pharmacological effect of the spongious biohybrid matrices was determined on an experimental model of burns induced to Wistar rats. The SEM images showed a porous structure with interconnected pores. Collagen sponges present a structure with pore sizes between 20 and 200 µm, which became more and more compact with polyvinyl alcohol addition. The FT-IR showed interactions between collagen and polyvinyl alcohol. The enzymatic degradation indicated that the most stable matrix is the one with the ratio 75:25 of collagen:polyvinyl alcohol (ACI75), the other ones being degradable in time. The kinetic data of indomethacin release from matrices were fitted with different kinetic models and highlighted a biphasic release of the drug. Such kinetic profiles are targeted in skin wound healing for which important aspects are impaired inflammation and local pain. The treatment with sponges associated with anti-inflammatory drug had beneficial effects on the healing process in experimentally induced burns compared to the corresponding matrices without indomethacin and the classical treated control group.