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Cilnidipine (CND), an anti-hypertensive drug, is known to have low oral bioavailability due to its poor aqueous solubility, low dissolution rate and high gut wall metabolism. In the present study, CND loaded compritol based nanoparticles (CND-CMP-NPs) were prepared by emulsification-solvent evaporation method applying the concepts of design of experiments. Critical factors affecting particle size and loading efficiency (LE%) were assessed by hybrid design approach, comprising of Mini Run Resolution IV design followed by Box-Behnken design. Particle size, PDI, zeta potential and LE% of optimized formulations of CND-CMP-NPs were 207.1 ± 2.9 nm, 0.27 ± 0.1, -22.2 ± 1.9 mV and 15.9 ± 1.3% respectively. No significant changes were observed in physical stability of NPs when stored at 25 °C/60% RH over a period of three months. Pharmacokinetic studies revealed that F abs of CND-CMP-NPs (0.66) was significantly higher than the free CND (0.27). The C max and AUC 0-∞ of CND-CMP-NPs (572.4 ± 25.3 ng/mL and 5588.6 ± 229.5 ng/mL × h) were significantly higher (P cal < 0.0001) as compared to free CND (363.6 ± 23.5 ng/mL and 2316.1 ± 163.6 ng/mL × h). MRT of CND-CMP-NPs (9.8 ± 0.9 h) was significantly higher (P cal < 0.0001) as compared to free CND (5.7 ± 0.5 h). Pharmacodynamic studies showed a maximum of 38% decrease in systolic blood pressure with more than 20% drop in systolic blood pressure sustained for a total duration of 64 h in the case of CND-CMP-NPs as compared to free CND. CND-CMP-NPs not only provide higher and sustained plasma levels of CND but also higher and sustained antihypertensive therapy as compared to free CND., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Species of the PST producing planktonic marine dinoflagellate genus Alexandrium have been intensively scrutinised, and it is therefore surprising that new taxa can still be found. Here we report a new species, Alexandrium diversaporum nov. sp., isolated from spherical cysts found at two sites in Tasmania, Australia. This species differs in its morphology from all previously reported Alexandrium species, possessing a unique combination of morphological features: the presence of 2 size classes of thecal pores on the cell surface, a medium cell size, the size and shape of the 6″, 1', 2⁗ and Sp plates, the lack of a ventral pore, a lack of anterior and posterior connecting pores, and a lack of chain formation. We determined the relationship of the two strains to other species of Alexandrium based on an alignment of concatenated SSU-ITS1, 5.8S, ITS2 and partial LSU ribosomal RNA sequences, and found A. diversaporum to be a sister group to Alexandrium leei with high support. A. leei shares several morphological features, including the relative size and shapes of the 6″, 1', 2⁗ and Sp plates and the fact that some strains of A. leei have two size classes of thecal pores. We examined A. diversaporum strains for saxitoxin production and found them to be non-toxic. The species lacked sequences for the domain A4 of sxtA, as has been previously found for non-saxitoxin producing species of Alexandrium., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Wide applications of Ruta graveolens L. in pharmaceutical industry has led to increased interest in large-scale plant production, with emphasis on use of in vitro cultures. Earlier reports describe use of in vitro germinated seedlings for raising shoot cultures and not regeneration. There is only a single regeneration protocol of R. graveolens; however, it employs conventional labour intensive techniques deterring automation. The aim of present investigation was to establish a cost effective protocol for large-scale plant production. We report for the first time a one-step protocol with improved regeneration efficiency for multiple shoots induction employing liquid culture systems. Effect of polyamines (putrescine and spermine) on growth and furanocoumarin was studied. Addition of spermine enhanced the number of multiple shoots formed (2.5-fold) and reduced the time taken by half. Spermine addition resulted in 1.47-fold in furanocoumarin production. The selected shoot line, RS2 was successfully scaled up to 5L in culture vessels, with 1.53-fold increase in biomass without affecting the productivity of these cultures. This proves to be a commercially feasible alternative to bioreactors for large-scale biomass and furanocoumarin production.

Retinoids profoundly affect the normal growth and differentiation of epithelial tissues. Retinoic acid receptor-gamma (RAR-gamma) is a member of a family of retinoid receptors, and has been shown to be expressed almost exclusively in skin. However, little is known about the cellular localization of this receptor in human skin. The authors studied the expression of RAR-gamma in normal skin and human skin tumors by Northern blot analysis and in situ hybridization. RAR-gamma mRNA was detected in normal skin as well as in cultures of neonatal keratinocytes. Using an oligonucleotide specific for the RAR-gamma cDNA isoform 1 (RAR-gamma 1), RAR-gamma 1 mRNA was localized to all layers of the epidermis, the outer root sheath of hair follicles, follicular hair bulbs, eccrine and sebaceous glands. Basal cell carcinoma constitutively expressed gamma-1 mRNA and one of seven squamous cell carcinomas showed loss of gamma-1 mRNA expression, relative to adjacent epithelium. By contrast, normal melanocytic nevi and tumor-associated lymphocytes expressed little or no RAR-gamma mRNA. These results suggest that RAR-gamma 1 may play an important role in the maintenance and differentiation of normal epidermis and skin appendages.