No abstract

The high incidence of prostate carcinogenesis has prompted the search for novel effective treatment approaches. We have employed curcumin (Curc) and diethylstilbestrol (DES) to synthesize a series of polyacetal (PA)-based combination conjugates for prostate cancer (PCa) treatment. Given their bihydroxyl functionalities, Curc and DES molecules were incorporated into a PA mainchain using a one-pot reaction between diols and divinyl ethers. The PA-conjugates released both drugs under acidic conditions, such as those found in the tumor microenvironment, endosomes, or lysosomes, while remaining stable at neutral pH 7.4. The drug ratio was optimized to achieve anticancer drug synergism with elevated cytotoxicity against LNCaP-hormone-dependent human PCa cells conferred via the induction of S phase cell cycle arrest by the upregulation of p53 and CDK inhibitors p21Waf/CIP1 and downregulation of cyclin D1. The application of rationally designed PA-Curc-DES combination conjugates represents a potentially exciting new treatment for prostate cancer.

The aim of the present study was to develop self-microemul sifying drug delivery systems (SMEDDS) of the extract of Moringa oleifera, a herbal medicinal plant. Kaempferol and quercetin, the flavonoids present in the leaf extract of M. olei fera, were chosen as markers for quantification. The optimized formulation of SMEDDS consisted of propylene glycol dicaprylocaprate, polysorbate 80, and polyethylene glycol 400 (PEG 400) in a percentage ratio of 20:60:20 (m/m). SMEDDS emulsified immediately (within 20 s) after dilution in water, resulting in transparent microemulsions with a droplet size of 49 nm. SMEDDS could increase the solubility of kaempferol and quercetin to nearly 100 % within 15 min, whereas only a 30 % improvement in solubility was achieved in the case of crude extract. These results demonstrated SMEDDS to be a promising strategy to improve the solubility of M. oleifera extract-derived drugs, which, in turn, could prove beneficial to the herbal medicine field.

The purpose of this research was to develop a hydrogel containing the extract of Gac fruit (Momordica cochinchinensis Spreng) with appropriate physicochemical properties and good dermatological efficacy. The Gac aril fruit was extracted by maceration in dichloromethane, and its antioxidant activity was determined through a DPPH assay. The very low water-solubility of the Gac extract is responsible for its incompatibility with the hydrogel. To overcome this drawback, Labrafac TM PG and Tween 60 were used to develop the hydrogel due to their potent potential for solubilizing the Gac extract. The prepared hydrogels displayed good physical properties, a homogenous orange gel, appropriate pH, and viscosity. After storage in an accelerated condition for six months, the hydrogels of the Gac extract had physical stability and high remaining amounts of beta-carotene and lycopene within the range of 90.25 -94.61%. The skin efficacy of hydrogel containing the Gac fruit extract was found using 14 healthy female volunteers over a 30-day period of daily application. Topical application of the hydrogel containing the Gac fruit extract, which contains antioxidants, significantly moisturizes the skin and enhanced its elasticity (p ≤ 0.05; ANOVA). This makes it suitable for use as a skin care product.

Palm fruits (Elaeis guineensis) comprise antioxidants that can be used as skin care agents. This study developed a cosmeceutical cream containing E. guineensis extract, loaded with solid lipid nanoparticles (SLNs), and assessed its efficacy on female volunteers. The E. guineensis extract exhibited a good antioxidant activity with high levels of vitamin E, β-carotene, and palmitic acid. Day and night creams containing E. guineensis fruit extract, loaded with SLNs, were formulated and exhibited acceptable physical characteristics and good stability. Subsequently, their clinical efficacy and safety were evaluated on female volunteers. Both creams were non-irritating and had good cutaneous compatibility. Skin hydration, transepidermal water loss (TEWL), skin elasticity, melanin index, and skin texture were measured before and 30 min after the first application, as well as after 7, 14, and 30 days of daily application. A satisfactory survey was implemented using a questionnaire, and volunteer satisfaction scores were high for the product’s performance. Overall, the results showed that skin hydration, TEWL, cutaneous elasticity, and melanin index were improved, compared to the baseline data, after 30 days. Thus, the formulated facial day and night creams made the skin moist, reduced wrinkles, increased elasticity, and cleared the skin to the consumers’ satisfaction.

Mefenamic acid (MA), a member of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), has been widely use to relief pain and inflammation. Its medical uses are limited by poor aqueous solubility resulting in low bioavailability and gastric irritation. The aim of this study was to develop a mefenamic acid delayed-release matrix tablet formulation using solid dispersion (SD). Delayed-release drug delivery systems were designed to retard drug release in upper gastrointestinal tract avoiding gastrointestinal (GI) adverse reactions. SDs of MA were successfully prepared by solvent evaporation method employing methanol as a solvent. SDs incorporated surfactant and super disintegrant gave much higher rates of dissolution than SDs with combined carriers (PEG and surfactant), SD containing PEG and pure drug, respectively. The optimal SD containing MA:PEG4000:poloxamer188:crospovidone in the ratio 1:8:1:3 exhibited higher amount of drug release up to 8-fold compared with pure MA. FTIR and DSC were performed to identify the physicochemical interaction between drug and polymers. The resulting data justified that no change in the chemical structure of MA and the crystalline MA transformed into the amorphous state after preparation. The formulation F4 delayed-release tablet comprising SD of MA dissolved less than 4 % in artificial gastric fluid in the initial 2 h and released more than 95 % at 3 h in the artificial intestinal fluid. Accordingly, formulation F4 containing polyethylene oxide as a time-controlled matrix-forming polymer was a promising delayed-release solid dispersion system of MA. HIGHLIGHTS The present study demonstrated a mefenamic acid delayed-release matrix tablet formulation using solid dispersion (SD) The optimal SD of mefenamic acid exhibited higher amount of drug release (8-fold) compared with that of the pure drug The tablet formulation F4 containing polyethylene oxide is capable of releasing mefenamic acid in a typical delayed-release profile GRAPHICAL ABSTRACT