No abstract

Sesamol has been studied extensively in the past two decades for its curative role in various diseases owing to its antioxidant potential. In vitro and in vivo pre-clinical studies indicate diverse role of sesamol in ailments connected by a common denominator of oxidative stress. These include antioxidant, anti-mutagenic, neuroprotective, hepatoprotective, cardioprotective, chemopreventive and anti-ageing properties. However, in depth investigation of its important characteristics including its oral pharmacokinetics is warranted, before evaluating this molecule for clinical application. The present study was undertaken to determine the physicochemical properties viz. solubility, log P, pK a and distribution coefficient of sesamol, coupled with its regional permeability through rat GIT. Single dose oral pharmacokinetic and tissue distribution studies of sesamol were also conducted in rats. The results indicate sesamol to be a molecule with appropriate aqueous solubility ($38.8 mg mL À1 ) and log P (1.29); the pK a of sesamol was found to be 9.79 and it exhibited a distribution coefficient of >1. Sesamol was well absorbed throughout the GIT and showed an oral bioavailability of 95.61%. Sesamol is widely distributed in rat tissue with the highest concentration in the kidneys followed by lungs, brain, and liver. In spite of a favorable bioprofile, the wide distribution, small t 1/2 and fast clearance of sesamol indicate a need for packaging it into a suitable delivery system.

Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN.

Lactobacillus acidophilus (LAB) loaded alginate floating beads (FBs) were developed with an intent to (i) preserve their viability during manufacture and upon exposure to adverse physiological conditions existing in the stomach, (ii) achieve an increased stay of the system in the stomach for improved pharmacodynamics and to provide for their effective establishment within the gastric mucosa. In vitro characterization of developed beads was performed in terms of entrapment efficiency, buoyancy, and surface as well as cross sectional morphology and viability studies of LAB in a gastric environment. The developed system was evaluated and was found to be significantly better in an experimental model of cold restraint stress (CRS) induced gastric ulcer model in terms of ulcer index, hemorrhagic streak length, histopathological and biochemical markers and their cross talk with reactive oxygen/nitrogen species. The present study emphasizes the advantages and future potential of probiotic loaded FBs in gastric disorders.