Biosynthesis and extraction of high-value carotenoid from algae.

Algae possess a considerable potential as bio-refinery for the scale-up production of high-value natural compounds like-carotenoids. Carotenoids are accessory pigments in the light-harvesting apparatus and also act as antioxidants and photo-protectors in green cells. They play important roles for humans, like-precursors of vitamin A, reduce the risk of some cancers, helps in the prevention of age-related diseases, cardiovascular diseases, improve skin health, and stimulates immunity. To date, about 850 types of natural carotenoid compounds have been reported and they have approximated 1.8 billion US$ of global market value. In comparison to land plants, there are few reports on biosynthetic pathways and molecular level regulation of algal carotenogenesis. Recent advances of algal genome sequencing, data created by high-throughput technologies and transcriptome studies, enables a better understanding of the origin and evolution of de novo carotenoid biosynthesis pathways in algae. Here in this review, we focused on, the biochemical and molecular mechanism of carotenoid biosynthesis in algae. Additionally, structural features of different carotenoids are elaborated from a chemistry point of view. Furthermore, current understandings of the techniques designed for pigment extraction from algae are reviewed. In the last section, applications of different carotenoids are elucidated and the growth potential of the global market value of carotenoids are also discussed.

Single-dose, two-way crossover, bioequivalence study of Mycophenolate mofetil 500 mg tablet under fasting conditions in healthy male subjects.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunosuppressant indicated for prophylaxis of acute organ transplant rejection. Generic MMF is less costly than the branded product, but European regulatory authorities require bioequivalence studies for the marketing of generics. OBJECTIVES: The aims of the 2 studies reported were to assess the dissolution and bioavailability of a generic (test) and branded (reference) formulation of MMF 500 mg. METHODS: An in vitro analytical dissolution profile test was conducted comparing 500 mg MMF test drug with a reference drug. A separate single-dose, randomized, open-label, 2-way crossover study involving fasting, healthy, adult male volunteers was conducted. Two study periods-1 test drug period and 1 reference drug period-were separated by a 14-day washout period. Blood samples were collected for up to 60 hours after drug administration for the determination of MMF and mycophenolic acid (MPA) pharmacokinetics. Concentrations of the analytes were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method; pharmacokinetic parameters were calculated using noncompartmental analysis; C(max), AUC(0-t), and AUC(0-∞) were the primary evaluation criteria. Bioequivalence was assumed if the 90% confidence intervals (CIs) for the test/reference ratios of natural logarithm transformed values (obtained using ANOVA) were between 80% and 125%, per European regulations for bioequivalence. Tolerability was monitored throughout the study. RESULTS: The dissolution profiles of the test drug matched those of the reference drug at 4 pH levels. In the bioequivalence study, a total of 126 male subjects were dosed, and 117 subjects completed the study. The 90% CIs for MPA were C(max), 94.13% to 116.46%; AUC(0-t), 98.26% to 102.36%; and AUC(0-∞), 97.85% to 101.99%. These values met with the European regulatory definition of bioequivalence. Reported adverse events were similar in both the test and reference drugs. CONCLUSIONS: This single-dose study found that the test and reference MMF 500 mg tablets met the European regulatory criteria for assuming bioequivalence in fasting, healthy, male subjects. Both formulations were well tolerated. (Clinical Trials Registry - India [CTRI]: 2011/03/002211).

Nanosomal Amphotericin B is an efficacious alternative to Ambisome for fungal therapy.

Amphotericin B was formulated in lipids (Nanosomal Amphotericin B) without using any detergent or toxic organic solvents during the preparation. Electron microscopy and particle size determination of Nanosomal Amphotericin B showed a homogeneous population of nanosized particles below 100 nm. Hemolysis assay indicated that Nanosomal Amphotericin B causes significantly less lysis of red blood cells than Amphotericin B deoxycholate and was comparable to Ambisome. A maximum daily dose of Nanosomal Amphotericin B at 5 mg/kg in rabbits and 10 mg/kg in mice for 28 days showed no symptoms of toxicity, mortality or significant body weight reduction. Hematological and gross pathological analysis of tissues revealed no abnormalities attributable to the drug treatment. Nanosomal Amphotericin B and Ambisome were injected (iv) at 2 mg/kg consecutively for 5 days into mice infected with Aspergillus fumigatus. The treatment resulted in 90% survival with Nanosomal Amphotericin B and only 30% survival with Ambisome after 10 days of fungal infection. However, all of the 10 control mice which were not treated with Amphotericin B died within 5 days of fungal infection. Nanosomal Amphotericin B is safe, cost effective and provides an alternative option for treatment of fungal disease.

Polyoxyl 60 hydrogenated castor oil free nanosomal formulation of immunosuppressant Tacrolimus: pharmacokinetics, safety, and tolerability in rodents and humans.

OBJECTIVE: Develop Nanosomal formulation of Tacrolimus to provide safer alternative treatment for organ transplantation patients. Investigate safety, tolerability and pharmacokinetics of Nanosomal Tacrolimus formulation versus marketed Tacrolimus containing polyoxyl 60 hydrogenated castor oil (HCO-60) that causes side effects. METHODS: Nanosomal Tacrolimus was prepared in an aqueous system. The particle size was measured by Particle Sizing Systems and structure morphology was determined by freeze-fracture electron microscopy. Investigational safety studies were conducted in mice and rats. Safety and pharmacokinetics of Nanosomal Tacrolimus were also evaluated in healthy human subjects. RESULTS: The morphology of Nanosomal Tacrolimus showed a homogeneous population of nanosized particles with mean particle size of less than 100 nm. A 14 day consecutive administration of Nanosomal Tacrolimus up to 5 and 10mg/kg dose in rats and mice respectively, resulted in no mortality. Nanosomal Tacrolimus in human studies showed that it is safe and the pharmacokinetics profile is similar to the marketed HCO-60 based Tacrolimus. No significant change in peripheral blood lymphocyte percentage was noted in either mice or healthy human male subjects. CONCLUSIONS: Nanosomal Tacrolimus is well characterized product which provides a new treatment option. It contains no alcohol or surfactants like HCO-60. Thus, Nanosomal Tacrolimus presents a new and improved therapeutic approach for organ transplant patients compared to the marketed HCO-60 based Tacrolimus product.