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Miguel Xavier,1 Lorena García-Hevia,1 Isabel R Amado,1,2 Lorenzo Pastrana,1 Catarina Gonçalves1 1Department of Life Sciences, International Iberian Nanotechnology Laboratory, Braga 4715-330, Portugal; 2Department of Food and Analytical Chemistry, Faculty of Sciences, University of Vigo, Ourense 32004, SpainCorrespondence: Catarina GonçalvesDepartment of Life Sciences, International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, Braga 4715-330, PortugalEmail catarina.goncalves@inl.intBackground: Oral administration remains the most common mode of drug delivery. However, orally administered bioactive compounds must first survive digestion and then be absorbed at the intestine in order to reach other tissues or organs. The efficiency of both processes can be improved by encapsulation or conjugation with polymeric nanoparticles. Here we report the synthesis of amphiphilic hyaluronic acid (HyA) nanogels as nanocarriers for drug delivery.Methods: HyA nanogels were prepared by self-assembly from amphiphilic HyA conjugates produced by grafting hydrophobic alkyl chains to the HyA backbone. The dye Cy5.5 was covalently bonded and used for tracking. The nanogels were characterised according to their structure, size and zeta potential, as well as biocompatibility towards an intestinal epithelial cell line. The uptake and intestinal permeability of the nanogels were assessed using in vitro models, which physiological relevance was verified regarding the morphology of the epithelium, the production of mucus, the expression of occludin and the transepithelial electrical resistance.Results: The covalent binding of Cy5.5 did not affect significantly the size and surface charge of the nanogels at 125.1 ± 3.2 nm and −57.6 ± 6.2 mV respectively after labelling. Studies of biocompatibility showed that the nanogels were non-toxic to Caco-2 cells up to the concentration of 0.1 mg∙mL−1. The presence of mucus affected the nanogel uptake and highlighted the importance of considering mucus-producing cells in in vitro intestinal models. The uptake or adsorption to a Caco-2/HT29-MTX co-culture (8.1%) was higher than with single Caco-2 cell cultures (4.3%). Interestingly, both models led to minute (

Abstract Background In the current Physical Activity Guidelines (PAG) for moderate- and vigorous-intensity physical activity (MVPA), abrupt transition from ≥ 60 min/day [youth PAG] to ≥ 150 min/week (≥ 22 min/day on average) [adult PAG] during emerging adulthood is poorly justified. The aim of this study was to examine body fat mass changes according to whether meeting the youth and adult PAGs in late adolescence (age 18 years) to early adulthood (age 22 years). Methods The study sample included 2,099 participants (1,113 females) from the 1993 Pelotas (Brazil) Study. At ages 18 and 22 years, MVPA was measured using wrist-worn accelerometry and fat mass was measured using dual-energy X-ray absorptiometry. MVPA at age 18 was categorized into two groups: 0–59 or ≥ 60 min/day (no [N] or yes [Y] for meeting the youth recommendation, respectively). MVPA at age 22 was categorized into three groups: 0–21, 22–59, or ≥ 60 min/day (N, Y22, or Y60 for not meeting the adult recommendation, meeting the adult recommendation, or meeting the youth recommendation, respectively). The combination of these groups created six MVPA groups (N&N, N&Y22, N&Y60, Y&N, Y&Y22, and Y&Y60). Sex-specific multivariable linear regression analyses were conducted to estimate change in fat mass index (FMI) from age 18 to 22 years in the six MVPA groups. Results Among males, compared to Y&Y60 (FMI increase = 1.2 kg/m2 [95% CI = 1.0, 1.4]), Y&Y22 and Y&N had larger FMI increases (1.9 [1.6, 2.1] and 1.9 [1.2, 2.5], respectively). Among females, Y&Y60 and Y&Y22 had an equal FMI increase (1.6 [1.4, 1.9] for both groups), while Y&N had a larger FMI increase (2.4 [1.8, 3.0]). Conclusions These findings suggest that among those who were active in late adolescence, engaging in ≥ 22 min/day of MVPA in adulthood is associated with lower body fat gain for females, but not for males.