Randomized, double-blind clinical trial evaluating the impact of freeze-dried garlic extract capsules on blood pressure, lipid profile, and nitric oxide levels in individuals at risk for hypertension.

OBJECTIVES: Hypertension, substantially heightens the risk of cardiovascular disease. This study aims to evaluate the effectiveness of freeze-dried garlic extract in blood pressure and lipid profiles in prehypertensive individuals. METHODS: Participants (age of 30-70 years) were allocated to intervention (n=47) or control (n=49) groups. The intervention group received two capsules of freeze-dried garlic extract daily for eight weeks, while the control group received identical placebo capsules. Primary outcomes, SBP, DBP, PP, MAP, TC, TG, LDL and HDL levels, serum NO levels, were assessed at baseline, four weeks, and eight weeks. RESULTS: At the end of study, results showed significant changes in the values of SBP, DBP, and MAP except for PP. In comparison to those who received the placebo, a significant drop in SBP, DBP (p<0.001), and MAP (p<0.001) was observed in the intervention group. Also, there were significant changes in TG, LDL, TC, and HDL levels in the interventional group. A noticeable decline was reported in TG (p<0.001), LDL (p<0.001), and TC (p<0.001), while HDL levels increased (p<0.001) in the intervention group compared to those receiving the placebo. Following garlic supplementation, a significant increase in blood NO levels was reported in the intervention group (p<0.001). CONCLUSIONS: The study showed that garlic supplementation was effective in lowering blood pressure, improving lipid profile, and increasing nitric oxide levels in prehypertensive participants. These results indicate that garlic could be a valuable complementary therapy for managing prehypertension.

In vivo assessment of bone repair by an injectable nanocomposite scaffold for local co-delivery of autologous platelet-rich plasma and calcitonin in a rat model.

BACKGROUND: Gellan gum is obtained from the bacterium Sphingomonas elodea and is a polysaccharide with carboxylic acid functional groups. The goal of this project was to investigate the osteoinductive effect of local administration of calcitonin through an injectable scaffold of gellan gum containing salmon calcitonin loaded in silsesquioxane nanoparticles, hydroxyapatite, and platelets rich plasma. METHODS: The femur of rats was defected by creating a 2 × 5 mm2 hole using an electric drill. The defect was filled with an injectable hydrogel scaffold composed of gellan gum enriched with salmon calcitonin loaded in silsesquioxane nanoparticles, hydroxyapatite, platelets rich plasma, and then the radiologic images were taken. Bone densitometry and the histologic studies were carried out by Hematoxylin & Eosin test. Biochemical analysis was done to measure the serum alkaline phosphatase (ALP), calcium, and calcitonin concentration. RESULTS: Healing of the bone defects and bone densitometry in the treated group by calcitonin-loaded scaffold was significantly higher (p < 0.05) and bone formation occupied 75% of the defect was greater than in other groups. Serum ALP and calcium levels in the scaffold-loaded calcitonin group were more than in the other groups (p < 0.05). The osteogenic marker genes also increased significantly (p < 0.05) with free calcitonin and the scaffold. CONCLUSIONS: Gellan gum-based scaffold loaded with calcitonin may be considered a promising local treatment to progress bone formation in repairing skeletal injuries.

Calcitonin-loaded octamaleimic acid-silsesquioxane nanoparticles in hydrogel scaffold support osteoinductivity in bone regeneration.

Novel osteoinductive scaffolds fabricated using the benefits of tissue engineering techniques accompanied by utilizing drugs can accelerate bone regeneration. The purpose of this study was to load salmon calcitonin (sCT) in octamaleimic acid-silsesquioxane (OMA-POSS) nanoparticles and enrich the hydrogel scaffold based on hydroxyapatite, Gelrite® and platelet-rich plasma (PRP) for use in bone tissue engineering. The loading efficiency, release percentage, particle size and zeta potential of the nanoparticles were evaluated. The proliferation of seeded MG-63 osteoblast cells on the designed scaffold, its cytotoxicity and osteo-conductivity were studied by alkaline phosphatase measurement and Alizarin red staining. The expression of cellular osteogenic markers such as collagen 1 (COL1A1), osteocalcin (BGLAP) and osteopontin (SPP1) was examined using reverse transcription polymerase chain reaction. The results revealed that the particle size of the nanoparticles varied between 94.2 and 199.2 nm and their negative surface charge increased after drug conjugation. The osteoblast cell proliferation and calcium granule production in the optimum formulation were significantly higher in comparison with the control group (p < 0.05). Osteogenic markers increased significantly after a specific number of days of cell culture compared to the control group (p < 0.05). The results also showed the potential of the designed scaffold in bone tissue engineering.

Polyhedral Oligomeric Silsesquioxane /Platelets Rich Plasma/Gelrite-Based Hydrogel Scaffold for Bone Tissue Engineering.

BACKGROUND: Polyhedral oligomeric silsesquioxane (POSS) is a monomer with silicon structure and an internal nanometric cage. OBJECTIVE: The purpose of this study was to provide an injectable hydrogel that could be easily located in open or closed bone fractures and injuries, and also to reduce the possible risks of infections caused by bone graft either as an allograft or an autograft. METHODS: Various formulations of temperature sensitive hydrogels containing hydroxyapatite, Gelrite, POSS and platelets rich plasma (PRP), such as the co-gelling agent and cell growth enhancer, were prepared. The hydrogels were characterized for their injectability, gelation time, phase transition temperature and viscosity. Other physical properties of the optimized formulation including compressive stress, compressive strain and Young's modulus as mechanical properties, as well as storage and loss modulus, swelling ratio, biodegradation behavior and cell toxicity as rheometrical parameters were studied on human osteoblast MG-63 cells. Alizarin red tests were conducted to study the qualitative and quantitative osteogenic capability of the designed scaffold, and the cell adhesion to the scaffold was visualized by scanning electron microscopy. RESULTS: The results demonstrated that the hydrogel scaffold mechanical force and injectability were 3.34±0.44 Mpa and 12.57 N, respectively. Moreover, the scaffold showed higher calcium granules production in alizarin red staining compared to the control group. The proliferation of the cells in G4.5H1P0.03PRP10 formulation was significantly higher than in other formulations (p<0.05). CONCLUSION: The optimized Gelrite/Hydroxyapatite/POSS/PRP hydrogel scaffold has useful impacts on osteoblasts activity, and may be beneficial for local drug delivery in complications including a break or bone loss.

Crystal Engineering for Enhanced Solubility and Bioavailability of Poorly Soluble Drugs.

BACKGROUND: Crystal engineering is dealing with the creation of new structures and new properties in drug molecules through inter-molecular interactions. Researchers of pharmaceutical sciences have used this knowledge to alter the structure of crystalline medications in order to remedy the problems of more than 40% of the new designed drugs which suffer from low solubility and consequently, low bioavailability which have limited their clinical application. METHODS: This review covers a broad spectrum of aspects of the application of crystal engineering in pharmaceutics and includes a comprehensive wide range of different techniques used in crystal engineering of active pharmaceutical ingredients (API) to compensate the low water solubility and bioavailability of drugs related specially to class II of biopharmaceutical classification system (BCS). RESULTS: These techniques include; crystalline habit modification, polymorphism, solvates and hydrates, cocrystals, surface modification, crystallization, spherical agglomeration, liquisolid crystals and solid dispersions which are introduced and discussed in this review article. CONCLUSION: Each of these techniques has advantages and limitations which are emphasized on them.

Nanocrystalization of Pioglitazone by Precipitation Method.

BACKGROUND: Poor solubility in aqueous medium limits the use of many drugs. Different methods have been adopted to promote the rate of dissolution of slightly water soluble drugs. Crystallization improves solubility, and bioavailability by increasing the surface area of slightly water soluble drugs. Pioglitazone (PGZ), which is a class II Biopharmaceutical Classification System drug has a slight solubility in water and a slow rate of dissolution, which may have a negative effect on its metabolism leading to a therapeutic failure. AIM: The aim of this study was to improve the solubility of PGZ-HCl; an antidiabetic drug using precipitation method. MATERIALS AND METHODS: Formulations were prepared with polyethylene glycol 6000 and isomalt using different speed of homogenizer and quantity of solvent by precipitation method. Drug-polymer interactions were examined using differential scanning calorimetry (DSC), and Powder X-Ray Diffraction (PXRD). Surface structure were shown by SEM photographs. RESULTS: The particle size was significantly decreased and solubility was enhanced with increase speed, ethanol solvent and increase stabilizer, however very high amount of stabilizer resulted in a decrease in solubility. CONCLUSION: This result however showed that solid dispersion technique is a potential method for increasing dissolution profile of a poorly aqueous soluble agent.