Properties, Extraction Methods, and Delivery Systems for Curcumin as a Natural Source of Beneficial Health Effects.

This review discusses the impact of curcumin-an aromatic phytoextract from the turmeric (Curcuma longa) rhizome-as an effective therapeutic agent. Despite all of the beneficial health properties ensured by curcumin application, its pharmacological efficacy is compromised in vivo due to poor aqueous solubility, high metabolism, and rapid excretion that may result in poor systemic bioavailability. To overcome these problems, novel nanosystems have been proposed to enhance its bioavailability and bioactivity by reducing the particle size, the modification of surfaces, and the encapsulation efficiency of curcumin with different nanocarriers. The solutions based on nanotechnology can improve the perspective for medical patients with serious illnesses. In this review, we discuss commonly used curcumin-loaded bio-based nanoparticles that should be implemented for overcoming the innate constraints of this natural ingredient. Furthermore, the associated challenges regarding the potential applications in combination therapies are discussed as well.

Methylene blue in anticancer photodynamic therapy: systematic review of preclinical studies.

Background: Methylene blue has a long history of clinical application. Thanks to phenothiazine chromophore, it has potential in photodynamic anticancer therapy. In spite of the growing body of literature that has evaluated the action of this dye on different types of cancer, the systematic understanding of this problem is still lacking. Therefore, this systematic review was performed to study the efficacy of methylene blue in photodynamic anticancer therapy. Methods: This systematic review was carried out in accordance with the PRISMA guidelines, and the study protocol was registered in PROSPERO (CRD42022368738). Articles for the systematic review were identified through the PubMed database. SYRCLE's risk of bias tool was used to assess the studies. The results of systematic analysis are presented as narrative synthesis. Results: Ten studies met the inclusion criteria and these full texts were reviewed. In the selected articles, the dosage of dye infusion ranged from 0.04 to 24.12 mg/kg. The effectiveness of photodynamic therapy with methylene blue against different types of cancer was confirmed by a decrease in tumor sizes in seven articles. Conclusion: The results of the systematic review support the suggestions that photodynamic therapy with methylene blue helps against different types of cancer, including colorectal tumor, carcinoma, and melanoma. In cases of nanopharmaceutics use, a considerable increase of anticancer therapy effectiveness was observed. The further research into methylene blue in photodynamic anticancer therapy is needed. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=368738), identifier (CRD42022368738).

Nanopharmaceutics: Part I-Clinical Trials Legislation and Good Manufacturing Practices (GMP) of Nanotherapeutics in the EU.

The latest advances in pharmaceutical technology are leading to the development of cutting edged approaches to produce what is now known as the "Holy Grail" of medicine-nanopharmaceutics. Over the latest decade, the pharmaceutical industry has made important contributions to the scale up of these new products. To ensure their quality, efficacy, and safety for human use, clinical trials are mandatory. Yet, regulation regarding nanopharmaceuticals is still limited with a set of guidelines being recently released with respect to compliance with quality and safety. For the coming years, updates on regulatory issues about nanopharmaceuticals and their use in clinical settings are expected. The use of nanopharmaceuticals in clinical trials depends on the approval of the production methods and assurance of the quality of the final product by implementation and verification of the good manufacturing practices (GMP). This review addresses the available legislation on nanopharmaceuticals within the European Union (EU), the GMP that should be followed for their production, and the current challenges encountered in clinical trials of these new formulations. The singular properties of nanopharmaceuticals over their bulk counterparts are associated with their size, matrix composition, and surface properties. To understand their relevance, four main clinical trial guidelines, namely, for intravenous iron-based nanopharmaceuticals, liposomal-based nanopharmaceuticals, block copolymer micelle-based nanopharmaceuticals, and related to surface coating requirements, are described here.

Nanopharmaceutics: Part II-Production Scales and Clinically Compliant Production Methods.

Due the implementation of nanotechnologies in the pharmaceutical industry over the last few decades, new type of cutting-edge formulations-nanopharmaceutics-have been proposed. These comprise pharmaceutical products at the nanoscale, developed from different types of materials with the purpose to, e.g., overcome solubility problems of poorly water-soluble drugs, the pharmacokinetic and pharmacodynamic profiles of known drugs but also of new biomolecules, to modify the release profile of loaded compounds, or to decrease the risk of toxicity by providing site-specific delivery reducing the systemic distribution and thus adverse side effects. To succeed with the development of a nanopharmaceutical formulation, it is first necessary to analyze the type of drug which is to be encapsulated, select the type matrix to load it (e.g., polymers, lipids, polysaccharides, proteins, metals), followed by the production procedure. Together these elements have to be compatible with the administration route. To be launched onto the market, the selected production method has to be scaled-up, and quality assurance implemented for the product to reach clinical trials, during which in vivo performance is evaluated. Regulatory issues concerning nanopharmaceutics still require expertise for harmonizing legislation and a clear understanding of clinically compliant production methods. The first part of this study addressing "Nanopharmaceutics: Part I-Clinical trials legislation and Good Manufacturing Practices (GMP) of nanotherapeutics in the EU" has been published in Pharmaceutics. This second part complements the study with the discussion about the production scales and clinically compliant production methods of nanopharmaceutics.

Development of Topical Nanocarriers for Skin Cancer Treatment Using Quality by Design Approach.

BACKGROUND: One of the most compelling medical challenges of this century is the treatment of cancer and among them, skin cancer is the most common type. Thus, current treatments need to be renewed continuously to handle this challenge. OBJECTIVE: This review presents considerations which can be employed during the development of nanosized formulations dedicated to the topical treatment of skin cancer. We aimed to collect and organize literature data on the treatment options for skin cancer in order to determine the required quality attributes of an effective dermal anticancer formulation. METHOD: With the consideration of the Quality by Design (QbD) approach related to the development of new pharmaceutical formulations, a cost-saving process ensuring a high-quality product taking into account patient expectations, industrial and regulatory aspects can be achieved. Furthermore, this concept is highly recommended by regulatory agencies. RESULTS: Our work discusses the current therapies, active agents, drug carrier systems, and evaluation methods in connection with the treatment of skin cancer and outlines Critical Quality Attributes which need to be considered during the development of a nanosized dermal anticancer formulation. CONCLUSION: The first part of this review summarizes the most important topical treatment therapies for skin cancer and highlights the future therapeutic perspectives, focusing on the benefits of nanotechnology and dermal administration. The second part outlines the critical points of nanosized dermal anticancer formulation development in the view of QbD approach. Our research emphasizes the application of QbD method for a rationalized and more effective anticancer formulation development process.

A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines.

Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL-1 and 2.4 mg mL-1 inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 µg mL-1.

Influencing Factors of the Pharmacokinetic Characters on Nanopharmaceutics.

BACKGROUND: Nano-pharmaceutics have been actively studied for the encapsulation and targeted delivery of drugs to improve the treatment strategies for various diseases. Because of the size, nano-pharmaceutics show some special characteristics of pharmacokinetics (PK). There are quite a number of studies focusing on the efficacy and toxicity of nano-pharmaceutics. However, only few of them investigated PK. METHOD: Literature search was conducted to summarize recent studies on PK of nano-pharmaceutics. RESULT: Both the efficacy and toxicity of nano-pharmaceutics are associated with their absorption, distribution, metabolism and elimination (ADME). Absorption mainly affects bioavailability, while distribution gears with target delivery. Both absorption and distribution play important roles in the efficacy of nano-pharmaceutics. Metabolism and elimination are the major influencing factors for the toxicity of nano-pharmaceutics. PK models and physiologically-based PK models can be powerful tools to analyze and predict the in vivo behavior of nano-pharmaceutics based on experimental data. CONCLUSION: Further research will be needed to investigate the underlying mechanism between the ADME processes of nano-pharmaceutics and their efficacy and toxicity.

All natural cellulose acetate-Lemongrass essential oil antimicrobial nanocapsules.

Nanocapsules and nanoparticles play an essential role in the delivery of pharmaceutical agents in modern era, since they can be delivered in specific tissues and cells. Natural polymers, such as cellulose acetate, are becoming very important due to their availability, biocompatibility, absence of toxicity and biodegradability. In parallel, essential oils are having continuous growth in biomedical applications due to the inherent active compounds that they contain. A characteristic example is lemongrass oil that has exceptional antimicrobial properties. In this work, nanocapsules of cellulose acetate with lemongrass oil were developed with the solvent/anti-solvent method with resulting diameter tailored between 95 and 185nm. Various physico-chemical and surface analysis techniques were employed to investigate the formation of the nanocapsules. These all-natural nanocapsules found to well bioadhere to mucous membranes and to have very good antimicrobial properties at little concentrations against Escherichia coli and Staphylococcus aureus.

Formation and stability of hesperidin nanoemulsion / 中草药

Objective: To prepare a new hesperidin nanoemulsion (HDN-NE) with glycyrrhizic acid as emulsifier, by which could develop a “new green nano-pharmaceutics” of hesperidin. Methods HDN-NE was prepared by high-speed shearing and high-pressure homogenization. The prescription of HDN-NE was optimized with particle size, PDI, and appearance as indexes. The physicochemical property and stability of HDN-NE prepared by the optimal prescription were studied. Results: The optimal prescription of HDN-NE was as follow: The content of hesperidin, glycyrrhizic acid, and oil phase were 0.1%, 0.3%, and 5%, respectively. The shear rate was 13 000 r/min, the cutting time was 2 min, the homogeneous pressure and times were 100 MPa and 6, severally. The result showed that the prepared HDN-NE had the mean size of (262.7 ± 3.1) nm, PDI of 0.234 ± 0.009, Zeta potential of (-35.42 ± 0.72) mV, and solubility of (460.3 ± 2.1) μg/mL. The physicochemical property study showed that the conductivity was (116.4 ± 1.7) μs/cm, the pH was 6.820 ± 0.008, and the turbidity was 451 cm-1 (n = 3). It was identified as O/W emulsion by dyeing method. The droplets were spherical and uniform by transmission electron microscopy. The stability study showed that HDN-NE had good stability. Conclusion: HDN-NE with glycyrrhizic acid as an emulsifier can significantly improve the solubility and stability of hesperidin, which is a new potential nano-drug with safety.