Skin penetration of caffeine from commercial eye creams and eye creams designed and optimized based on Hansen solubility parameters.

Computer-aided formulation design can streamline and speed up product development. In this study, ingredient screening and optimizing software, Formulating for Efficacy® (FFE), was used to design and optimize creams for the topical delivery of caffeine. FFE was set up to optimize lipophilic active ingredients, therefore, this study challenged the program's capabilities. The effect of two chemical penetration enhancers, including dimethyl isosorbide (DMI) and ethoxydiglycol (EDG), were studied based on their favorable Hansen Solubility Parameter physicochemical input parameters for the skin delivery of caffeine in the FFE® software application. Four oil-in-water emulsions containing 2% caffeine were formulated, one without a chemical penetration enhancer, one with five percent of DMI, one with five percent of EDG, and one with 2.5% of DMI and EDG each (DMI + EDG). Additionally, three commercial products were used as reference products. The cumulative amount of caffeine released and permeated, and the flux across Strat-M® membranes were determined using Franz diffusion cells. The eye creams had skin-compatible pH, excellent spreadability for the application area, were opaque emulsions with 14-17 µm droplet size, and were stable at 25 °C for 6 months. All four eye creams formulated released over 85% of caffeine in 24 h, outperforming the commercial products. DMI + EDG cream provided the highest permeation in vitro in 24 h, which was significantly higher than the commercial products (p < 0.05). FFE proved to be a valuable and quick tool to aid in the topical delivery of caffeine.

Microwave-Assisted Functionalization of Multi-Walled Carbon Nanotubes for Biosensor and Drug Delivery Applications.

Microwave-assisted synthetic methods have emerged as a popular technique for surface modification and the functionalization of multi-walled carbon nanotubes (MWCNTs) for diverse drug delivery applications. Microwave-induced functionalization of MWCNTs provides a high functionalization and requires less time than conventional techniques. Microwave methods are simple, fast, and effective for the covalent and noncovalent conjugation of MWCNTs with various biomolecules and polymers. The present review focuses on the synthetic and drug delivery applications of microwave irradiation techniques (MITs) for the functionalization of MWCNTs, using amino acids and other molecular frameworks containing amino groups, vitamins, proteins, epoxy moieties, metal nanoparticles, and polymers.

Oncology biosimilars: New developments and future directions.

Biologicals have become an integral part of cancer treatment both as therapeutic agents and as supportive care agents. It is important to know that biologics are large, complex molecular entities requiring extensive immunogenicity testing and pharmacovigilance strategies to ensure no immune response is evoked in the body. Oncology's pharmacological market is dominated by biologics; however, their high development and manufacturing costs are burdensome to health care systems. Biologics being the most expensive prescription drugs on the market limit the accessibility for necessary treatment in the case of many patients. As biologics patents expire, the development of biosimilars is underway in an effort to lower costs and enable patients to access new cancer therapies. Regulatory guidelines for biosimilars have now been established and are constantly being revised to address any issues, facilitating their robust development. Moreover, many scientific societies offer guidance to help stakeholders better understand current regulations and biosimilar's safety. Despite the potential cost benefits, lack of knowledge about biosimilars, and the possibility of immunogenicity have created an uncertain environment for healthcare professionals and patients. In this review, we provide an overview of relevant legislation and regulations, pharmacoeconomics, and stakeholder perceptions regarding biosimilars. The article also describes biosimilars in development, as well as the ones currently available on the market.

Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis.

A novel series of 4-anilinoquinazoline analogues, DW (1-10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.

Transdermal Delivery of Chemotherapeutics: Strategies, Requirements, and Opportunities.

Chemotherapeutic drugs are primarily administered to cancer patients via oral or parenteral routes. The use of transdermal drug delivery could potentially be a better alternative to decrease the dose frequency and severity of adverse or toxic effects associated with oral or parenteral administration of chemotherapeutic drugs. The transdermal delivery of drugs has shown to be advantageous for the treatment of highly localized tumors in certain types of breast and skin cancers. In addition, the transdermal route can be used to deliver low-dose chemotherapeutics in a sustained manner. The transdermal route can also be utilized for vaccine design in cancer management, for example, vaccines against cervical cancer. However, the design of transdermal formulations may be challenging in terms of the conjugation chemistry of the molecules and the sustained and reproducible delivery of therapeutically efficacious doses. In this review, we discuss the nano-carrier systems, such as nanoparticles, liposomes, etc., used in recent literature to deliver chemotherapeutic agents. The advantages of transdermal route over oral and parenteral routes for popular chemotherapeutic drugs are summarized. Furthermore, we also discuss a possible in silico approach, Formulating for Efficacy™, to design transdermal formulations that would probably be economical, robust, and more efficacious.

Blue light protection, part II-Ingredients and performance testing methods.

BACKGROUND: There are numerous cosmetic ingredients that have been identified to have blue light protection benefits. The urge to learn more about blue light protection claims has led to several substantiation test methods that can be utilized by companies to prove product efficacy. AIMS: Part II of this article provides up-to-date information on cosmetic ingredients that can provide protection from blue light, and methods companies can use to substantiate blue light protection claims. METHODS: An Internet search was completed using the Google Scholar database and a cosmetic ingredient supplier database (UL Prospector) for ingredients and relevant literature. RESULTS: Multiple ingredient categories, for example, algae-derived ingredients, UV filters, botanical extracts, antioxidants, and vitamins, are available on the market to fight against blue light-induced skin damage. There is not a formal standardized method to test for blue light protection; however, spectrophotometers, imaging devices, measuring oxidative stress, and visual evaluations are some of the methods being used today. CONCLUSIONS: The number of ingredients launched for blue light protection and new methods developed to test products for blue light protection claims is expected to increase in the near future as we are learning more about the mechanism of damage that occurs in the skin upon blue light exposure.

Blue Light Protection, Part I-Effects of blue light on the skin.

BACKGROUND: Blue light is emitted visible light between the wavelengths of 400 to 500 nm. The main source of blue light is sunlight, but digital screens, light-emitting diodes (LEDs), and fluorescent lighting serve as additional sources. Concerns about the negative effects of blue light on the skin have rapidly increased over the past 15 years, and consequently, the urge to learn more about this topic is increasing as well. AIMS: Part I of this article provides up-to-date information on the definition of blue light and the negative and positive effects of blue light on the skin. METHODS: An Internet search was completed using the Google scholar database for relevant literature. RESULTS: Blue light can be both harmful and beneficial to the skin, depending on intensity and wavelength. Short-term safety information is more readily available from clinical studies; however, the biological effects of repeated and/or longer-term exposure are not fully understood yet. CONCLUSIONS: Low-energy and low exposure times to high-energy blue light can help prevent skin diseases, while studies have revealed that longer exposure to high-energy blue light can increase the amount of DNA damage, cell and tissue death, and injury, eye damage, skin barrier damage, and photoaging.

Effect of Solvents on the In Vitro Sun Protection Factor and Broad-Spectrum Protection of Three Organic UV Filters.

Solvents play an essential role in the performance of ultraviolet (UV) filters. The goal of this study was to understand how the in vitro sun protection factor (SPF) and broad-spectrum protection of three organic UV filters (homosalate, ethylhexyl salicylate, and butyl methoxydibenzoylmethane) and a combination of these are influenced by solvents. Twenty-four solvents were selected based on the ingredient active gap for testing. Mixtures of UV filters and solvents were formulated, and in vitro SPF, wavelength of maximum absorbance, broad-spectrum protection, and spreadability were evaluated. Results indicate that in vitro SPF of organic sunscreens can be significantly enhanced by solvents. Relying on solubility data only was not found to be a good approach in this study. The most efficient solvents shared multiple similar structural characteristics, including ester bonds, conjugated structure, aromatic rings, and -CN groups; however, the absence of some of these structural elements did not necessarily prevent a solvent from being a booster. The wavelength of maximum absorbance was significantly shifted in the UVA range by most solvents, whereas minimal or no shift was observed in the UVB range. Results of this study provide practical information that can guide sunscreen formulators in selecting solvents for UV filters and making more effective sunscreens.