Innovative breakthroughs in nanotechnology are having a substantial impact in healthcare, especially for brain diseases where effective therapeutic delivery systems are desperately needed. Nanoparticle delivery systems offer an unmatched ability of not only conveying a diverse array of diagnostic and therapeutic agents across complex biological barriers, but also possess the ability to transport payloads to targeted cell types over a sustained period. In substance use disorder (SUD), many therapeutic targets have been identified in preclinical studies, yet few of these findings have been translated to effective clinical treatments. The lack of success is, in part, due to the significant challenge of delivering novel therapies to the brain and specific brain cells. In this review, we evaluate the potential approaches and limitations of nanotherapeutic brain delivery systems. We also highlight the examples of promising strategies and future directions of nanocarrier-based treatments for SUD.
Gut microbiota are affected by antibiotics and may modulate host energy metabolism. Male and female C57BL/6J mice (n=5∼11/group) were exposed to low-dose penicillin (LDP) via maternal drinking water from birth to 4 weeks (w) of age, and chronic changes in energy balance were examined using metabolic cages. Through 8w of age (Chow), LDP and Control mice had comparable fat mass, but male and female LDP mice showed significantly increased O2 consumption rates without changes in food intake and activity (Figure). At 9w of age, mice were given a high-fat diet (HFD; 45% fat by calories), and they began gaining adiposity with female LDP mice showing ∼40% lower fat mass than Controls. After 8w of HFD, male LDP group showed significantly elevated O2 consumption rates compared to Controls. Male LDP mice also showed marked reductions in food intake and activity, but these effects were no longer observed after 12w of HFD. In contrast, female LDP group had reduced O2 consumption rates compared to Controls after 4 and 8w of HFD without changes in food intake and activity.
In conclusion, these results indicate that early life exposure to penicillin modulates energy balance in young and mature mice, suggesting an important role of altered populations of gut microbiota in diet-induced obesity. Our findings also identify important gender-selective effects of early life antibiotic exposure on energy balance in mature mice.
Disclosure
H. Noh: None. S. Suk: None. R.H. Friedline: None. K. Inashima: None. D.A. Tran: None. A.M. Kim: None. S. Kim: None. S. Jeong: None. C. Uong: None. B.A. Ozkan: None. V. Kasina: None. K.P. Knowles: None. G. Perez-Perez: None. K. Lee: None. M.J. Blaser: None. J.K. Kim: None.
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