Impactos da quitosana e suas nanoformulações nas síndromes metabólicas: uma revisão

Abd El‐Hack, M. E.; Kamal, M.; Alazragi, R. S.; Alreemi, R. M.; Qadhi, A.; Ghafouri, K.; Azhar, W.; Shakoori, A. M.; Alsaffar, N.; Naffadi, H. M.; Taha, A. E.; Abdelnour, S. A.

M. E. Abd El‐Hack ^**e-mail: dr.mohamed.e.abdalhaq@gmail.com

Zagazig University, Faculty of Agriculture, Department of Poultry, Zagazig, Egypt

http://orcid.org/0000-0002-2831-8534

M. Kamal

Agricultural Research Center, Animal Production Research Institute, Dokki, Giza, Egypt

http://orcid.org/0000-0002-5618-7076

R. S. Alazragi

University of Jeddah, College of Science, Department of Biochemistry, Jeddah, Saudi Arabia

http://orcid.org/0009-0002-9607-3353

R. M. Alreemi

University of Jeddah, College of Science, Department of Biochemistry, Jeddah, Saudi Arabia

http://orcid.org/0000-0002-9062-5674

A. Qadhi

Umm Al-Qura University, Faculty of Applied Medical Sciences, Clinical Nutrition Department, Makkah, Saudi Arabia

http://orcid.org/0000-0001-8482-3044

K. Ghafouri

Umm Al-Qura University, Faculty of Applied Medical Sciences, Clinical Nutrition Department, Makkah, Saudi Arabia

http://orcid.org/0000-0001-9420-3666

W. Azhar

Umm Al-Qura University, Faculty of Applied Medical Sciences, Clinical Nutrition Department, Makkah, Saudi Arabia

http://orcid.org/0000-0002-9247-2149

A. M. Shakoori

Umm Al-Qura University, Faculty of Applied Medical Sciences, Laboratory Medicine Department, Makkah, Kingdom of Saudi Arabia

http://orcid.org/0000-0002-3361-9243

N. Alsaffar

Mohammed Al-Mana College for Medical Sciences, Biochemistry and Molecular Biology Department, Dammam, Saudi Arabia

http://orcid.org/0009-0001-1525-7197

H. M. Naffadi

Umm Al-Qura University, College of Medicine, Department of Medical Genetics, Makkah, Kingdom of Saudi Arabia

http://orcid.org/0000-0003-4027-480X

A. E. Taha

Alexandria University, Faculty of Veterinary Medicine, Department of Animal Husbandry and Animal Wealth Development, Edfina, Egypt

http://orcid.org/0000-0002-0429-2587

S. A. Abdelnour

Zagazig University, Faculty of Agriculture, Department of Animal Production, Zagazig, Egypt

http://orcid.org/0000-0002-6873-0718

*e-mail: dr.mohamed.e.abdalhaq@gmail.com

Study Mode	Additive/dose	Findings	References
In vitro model	COS (1-3 kDa)	COS decreased lipid accumulation.	Cho et al. (2008)CHO, E.J., RAHMAN, A., KIM, S.W., BAEK, Y.M., HWANG, H.J., OH, J.Y., HWANG, H.S., LEE, S.H. and YUN, J.W., 2008. Chitosan oligosaccharides inhibit adipogenesis in 3T3-L1 adipocytes. Journal of Microbiology and Biotechnology, vol. 18, no. 1, pp. 80-87. PMid:18239421.
In vitro model	COS (1-3 kDa)	Inhibited adipocyte differentiation.
Mice	200 mg/kg of COS	COS can control diet intake, body weight gain, blood glucose, and lipid profiles.	Kumar et al. (2009)KUMAR, S.G., RAHMAN, M.A., LEE, S.H., HWANG, H.S., KIM, H.A. and YUN, J.W., 2009. Plasma proteome analysis for anti‐obesity and anti‐diabetic potentials of chitosan oligosaccharides in ob/ob mice. Proteomics, vol. 9, no. 8, pp. 2149-2162. http://dx.doi.org/10.1002/pmic.200800571. PMid:19296549. http://dx.doi.org/10.1002/pmic.200800571...
In vitro model	1, 10, 100, 500 and 1000 µg mL^-1	COS inhibited the differentiation of 3T3-L1 preadipocytes.	Kong et al. (2017)KONG, S., DING, C., HUANG, L., BAI, Y., XIAO, T., GUO, J. and SU, Z., 2017. The effects of COST on the differentiation of 3T3-L1 preadipocytes and the mechanism of action. Saudi Journal of Biological Sciences, vol. 24, no. 2, pp. 251-255. http://dx.doi.org/10.1016/j.sjbs.2016.09.008. PMid:28149159. http://dx.doi.org/10.1016/j.sjbs.2016.09...
Rates	COS capsules	COS capsules can regulate body weight gain, lipids, and serum alanine aminotransferase.	Pan et al. (2018)PAN, H., FU, C., HUANG, L., JIANG, Y., DENG, X., GUO, J. and SU, Z., 2018. Anti-obesity effect of chitosan oligosaccharide capsules (COSCs) in obese rats by ameliorating leptin resistance and adipogenesis. Marine Drugs, vol. 16, no. 6, pp. 198. http://dx.doi.org/10.3390/md16060198. PMid:29874843. http://dx.doi.org/10.3390/md16060198...
Mice	L MW COS(400 mg kg⁻¹)	COS regulated the dysfunctional gut microbiota and alleviated low-grade inflammation	He et al. (2020)HE, N., WANG, S., LV, Z., ZHAO, W. and LI, S., 2020. Low molecular weight chitosan oligosaccharides (LMW-COSs) prevent obesity-related metabolic abnormalities in association with the modification of gut microbiota in high-fat diet (HFD)-fed mice. Food & Function, vol. 11, no. 11, pp. 9947-9959. http://dx.doi.org/10.1039/D0FO01871F. PMid:33108433. http://dx.doi.org/10.1039/D0FO01871F...
Rats	GO2KA1 (200 to 800 µg/mL)	GO2KA1 may prevent diet-induced weight gain. Inhibited adipogenesis.	Lee et al. (2021)LEE, J.Y., KIM, T.Y., KANG, H., OH, J., PARK, J.W., KIM, S.C., KIM, M., APOSTOLIDIS, E., KIM, Y.C. and KWON, Y.I., 2021. Anti-obesity and anti-adipogenic effects of chitosan oligosaccharide (GO2KA1) in SD rats and in 3T3-L1 preadipocytes models. Molecules, vol. 26, no. 2, pp. 331. http://dx.doi.org/10.3390/molecules26020331. PMid:33440605. http://dx.doi.org/10.3390/molecules26020...
Rabbits	0.2 g/kg of chitosan	Chitosan increased triglyceride and HDL, improving the health status of NZW rabbits.	Kamal et al. (2023a) KAMAL, M., KISHK, W.H., KHALIL, H.A., ABDEL-KHALEK, A.M., AYOUB, M.A., SWELUM, A.A., ALQHTANI, A.H., BA-AWADH, H.A. and ABD EL-HACK, M.E., 2023a. Effect of dietary chitosan supplementation on productive and physiological performance parameters of growing New Zealand white rabbits. International Journal of Biological Macromolecules, vol. 230, pp. 123166. http://dx.doi.org/10.1016/j.ijbiomac.2023.123166. PMid:36623627. http://dx.doi.org/10.1016/j.ijbiomac.202...
chickens	14-28 g/kg of COS	COS increased the relative weight of the liver. Increased HDL and decreased abdominal fat.	Zhou et al. (2009)ZHOU, T.X., CHEN, Y.J., YOO, J.S., HUANG, Y., LEE, J.H., JANG, H.D., SHIN, S.O., KIM, H.J., CHO, J.H. and KIM, I.H., 2009. Effects of chitooligosaccharide supplementation on performance, blood characteristics, relative organ weight, and meat quality in broiler chickens. Poultry Science, vol. 88, no. 3, pp. 593-600. http://dx.doi.org/10.3382/ps.2008-00285. PMid:19211530. http://dx.doi.org/10.3382/ps.2008-00285...
Rates	5% chitosan /kg	Chitosan reduced the absorption of dietary fat and cholesterol in vivo.	Zhang et al. (2008)ZHANG, J., LIU, J., LI, L. and XIA, W., 2008. Dietary chitosan improves hypercholesterolemia in rats fed high-fat diets. Nutrition Research, vol. 28, no. 6, pp. 383-390. http://dx.doi.org/10.1016/j.nutres.2007.12.013. PMid:19083436. http://dx.doi.org/10.1016/j.nutres.2007....
Rates	5% chitosan /kg	Improve hypercholesterolemia.
Rates	450 mg/kg/day of CHNPs	CHNPs decreased body weight gain and serum lipid levels.	Abd El-Hack et al. (2020)ABD EL-HACK, M.E., EL-SAADONY, M.T., SHAFI, M.E., ZABERMAWI, N.M., ARIF, M., BATIHA, G.E., KHAFAGA, A.F., ABD EL-HAKIM, Y.M. and AL-SAGHEER, A.A., 2020. Antimicrobial and antioxidant properties of chitosan and its derivatives and their applications: a review. International Journal of Biological Macromolecules, vol. 164, pp. 2726-2744. http://dx.doi.org/10.1016/j.ijbiomac.2020.08.153. PMid:32841671. http://dx.doi.org/10.1016/j.ijbiomac.202...
Rabbits	TPP Tween-80	Drug-loaded NPs significantly lowered blood lipid levels compared to pure drug	Chen et al. (2020)CHEN, L., WANG, C. and WU, Y., 2020. Cholesterol (Blood lipid) lowering potential of Rosuvastatin chitosan nanoparticles for atherosclerosis: preclinical study in rabbit model. Acta Biochimica Polonica, vol. 67, no. 4, pp. 495-499. http://dx.doi.org/10.18388/abp.2020_5186. PMid:33090754. http://dx.doi.org/10.18388/abp.2020_5186...
Rabbits	Chitosan Ionotropic gelation
In vivo	Selenium Chitosan Chemical reduction	Reduced atherosclerotic lesions in ApoE-/-mice.	Xiao et al. (2021)XIAO, S., MAO, L., XIAO, J., WU, Y. and LIU, H., 2021. Selenium nanoparticles inhibit the formation of atherosclerosis in apolipoprotein E deficient mice by alleviating hyperlipidemia and oxidative stress. European Journal of Pharmacology, vol. 902, pp. 174120. http://dx.doi.org/10.1016/j.ejphar.2021.174120. PMid:33905703. http://dx.doi.org/10.1016/j.ejphar.2021....
In vivo	Selenium Chitosan Chemical reduction	Inhibited hyperlipidemia.
in vivo	NaTPP+Tween	Reduced triglycerides and LDL.	Oksal et al. (2020)OKSAL, E., PANGESTIKA, I., MUHAMMAD, T.S.T., MOHAMAD, H., AMIR, H., KASSIM, M.N.I. and ANDRIANI, Y., 2020. In vitro and in vivo studies of nanoparticles of chitosan-Pandanus tectorius fruit extract as new alternative treatment for hypercholesterolemia via Scavenger Receptor Class B type 1 pathway. Saudi Pharmaceutical Journal, vol. 28, no. 10, pp. 1263-1275. http://dx.doi.org/10.1016/j.jsps.2020.08.017. PMid:33132720. http://dx.doi.org/10.1016/j.jsps.2020.08...
in vivo	Chitosan powder	Increased HDL.

Study Mode	Additive/dose	Findings	References
Pigs	1000 ppm chitosan	Chitosan exhibited anti-obesogenic potential through alterations to appetite and feeding behavior affecting satiety signals.	Egan et al. (2016)EGAN, Á.M., O’DOHERTY, J.V., VIGORS, S. and SWEENEY, T., 2016. Prawn shell chitosan exhibits anti-obesogenic potential through alterations to appetite, affecting feeding behaviour and satiety signals in vivo. PLoS One, vol. 11, no. 2, e0149820. http://dx.doi.org/10.1371/journal.pone.0149820. PMid:26901760. http://dx.doi.org/10.1371/journal.pone.0...
Man	chitosan capsules (500 mg)	Reduced the mean body weight by up to 3 kg during the 90-day study period.	Trivedi et al. (2015)TRIVEDI, V.R., SATIA, M.C., DESCHAMPS, A., MAQUET, V., SHAH, R.B., ZINZUWADIA, P.H. and TRIVEDI, J.V., 2015. Single-blind, placebo controlled randomised clinical study of chitosan for body weight reduction. Nutrition Journal, vol. 15, no. 1, pp. 3. http://dx.doi.org/10.1186/s12937-016-0122-8. PMid:26747458. http://dx.doi.org/10.1186/s12937-016-012...
Man	chitosan capsules (500 mg)	Improvement in body composition, anthropometric parameters, and improvement in quality-of-life score.
Pigs	1000 ppm chitosan	Chitosan has affected potent anti-obesity/body weight control.	Egan et al. (2015)EGAN, Á.M., SWEENEY, T., HAYES, M. and O’DOHERTY, J.V., 2015. Prawn shell chitosan has anti-obesogenic properties, influencing both nutrient digestibility and microbial populations in a pig model. PLoS One, vol. 10, no. 12, e0144127. http://dx.doi.org/10.1371/journal.pone.0144127. PMid:26636332. http://dx.doi.org/10.1371/journal.pone.0...
Mice	COS (1.0 mg/mL, dissolved in water, about 200 mg/kg/d)	Improved glucose metabolism.	Zheng et al. (2018)ZHENG, J., YUAN, X., CHENG, G., JIAO, S., FENG, C., ZHAO, X., YIN, H., DU, Y. and LIU, H., 2018. Chitosan oligosaccharides improve the disturbance in glucose metabolism and reverse the dysbiosis of gut microbiota in diabetic mice. Carbohydrate Polymers, vol. 190, pp. 77-86. http://dx.doi.org/10.1016/j.carbpol.2018.02.058. PMid:29628262. http://dx.doi.org/10.1016/j.carbpol.2018...
Mice	COS (1.0 mg/mL, dissolved in water, about 200 mg/kg/d)	Reshaped the unbalanced gut microbiota of diabetic mice.
Mice	COS	Reduced the aggregation of hIAPP.	Meng et al. (2020)MENG, Q.Y., WANG, H., CUI, Z.B., YU, W.G. and LU, X.Z., 2020. Chitosan oligosaccharides attenuate amyloid formation of hIAPP and protect pancreatic β-cells from cytotoxicity. Molecules, vol. 25, no. 6, pp. 1314. http://dx.doi.org/10.3390/molecules25061314. PMid:32183067. http://dx.doi.org/10.3390/molecules25061...
Mice	COS	COS protected -cells from cytotoxicity of amyloidogenic hIAPP.
Mice	GO2KA1 (MW< 1000 Da)	GO2KA1 may prevent diabetes type 2, via the inhibition of carbohydrate hydrolysis enzymes.	Kim et al. (2014b)KIM, J.G., JO, S.H., HA, K.S., KIM, S.C., KIM, Y.C., APOSTOLIDIS, E. and KWON, Y.I., 2014b. Effect of long-term supplementation of low molecular weight chitosan oligosaccharide (GO2KA1) on fasting blood glucose and HbA1c in db/db mice model and elucidation of mechanism of action. BMC Complementary and Alternative Medicine, vol. 14, no. 1, pp. 272. http://dx.doi.org/10.1186/1472-6882-14-272. PMid:25074485. http://dx.doi.org/10.1186/1472-6882-14-2...
Rats	COS, (125-250 µg/25 µl, daily)	COS has antidiabetic.	Katiyar et al. (2011)KATIYAR, D., SINGH, B., LALL, A.M. and HALDAR, C., 2011. Efficacy of chitooligosaccharides for the management of diabetes in alloxan induced mice: a correlative study with antihyperlipidemic and antioxidative activity. European Journal of Pharmaceutical Sciences, vol. 44, no. 4, pp. 534-543. http://dx.doi.org/10.1016/j.ejps.2011.09.015. PMid:21964204. http://dx.doi.org/10.1016/j.ejps.2011.09...
Rats	COS, (125-250 µg/25 µl, daily)	COS has antihyperlipidemic and antioxidative activities.
Rats	COS, 500 mg/kg	COS reduced fasting blood glucose.	Ju et al. (2010)JU, C., YUE, W., YANG, Z., ZHANG, Q., YANG, X., LIU, Z. and ZHANG, F., 2010. Antidiabetic effect and mechanism of chitooligosaccharides. Biological & Pharmaceutical Bulletin, vol. 33, no. 9, pp. 1511-1516. http://dx.doi.org/10.1248/bpb.33.1511. PMid:20823566. http://dx.doi.org/10.1248/bpb.33.1511...
Rats	COS, 500 mg/kg	COS increased the insulin sensitivity index and improved oral glucose tolerance.
In vitro	chitosan NPs (100-500 nm)	Enhanced the general situation and diabetic symptoms.	Liu et al. (2007a)LIU, B., LIU, W.S., HAN, B.Q. and SUN, Y.Y., 2007a. Antidiabetic effects of chitooligosaccharides on pancreatic islet cells in streptozotocin-induced diabetic rats. World Journal of Gastroenterology, vol. 13, no. 5, pp. 725-731. http://dx.doi.org/10.3748/wjg.v13.i5.725. PMid:17278195. http://dx.doi.org/10.3748/wjg.v13.i5.725...
In vitro	chitosan NPs (100-500 nm)	Reduced the levels of blood and urine glucose.
In vitro	Insulin loading on NPs with chitosan.	Reduced the blood glucose level in a diabetic.	Lin et al. (2007)LIN, Y.H., MI, F.L., CHEN, C.T., CHANG, W.C., PENG, S.F., LIANG, H.F. and SUNG, H.W., 2007. Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery. Biomacromolecules, vol. 8, no. 1, pp. 146-152. http://dx.doi.org/10.1021/bm0607776. PMid:17206800. http://dx.doi.org/10.1021/bm0607776...
Rats	CN (3 mg kg^-1)/day	CN improved the impairment of lipid metabolism.	Salem et al. (2021)SALEM, S.A., DIAB, M.S.M., SHEHATA, S.H. and SOLIMAN, T.N., 2021. Nanochitosan effect on biomolecular, hypolipidemic in rats and incorporation in functional yogurt. Pakistan Journal of Biological Sciences, vol. 24, no. 5, pp. 548-561. http://dx.doi.org/10.3923/pjbs.2021.548.561. PMid:34486330. http://dx.doi.org/10.3923/pjbs.2021.548....
Pigs	2% of nano-chitosan	Nano-chitosan reduced fasting blood glucose.	Sami et al. (2022)SAMI, M.M., AL-KAZZAZ, F.F. and ABDULSATTAR, S.A., 2022. The effect of using Chitosan and Nano-chitosan synthesized from blue carb in the treatment of hyperglycemia and glomerulus of diabetic guinea pigs. Egyptian Journal of Chemistry, vol. 65, no. 6, pp. 55-58. http://dx.doi.org/10.21608/EJCHEM.2021.85130.4151. http://dx.doi.org/10.21608/EJCHEM.2021.8...
Pigs	2% of nano-chitosan	Chitosan and nano-chitosan improved the function of the kidney (urea and creatinine) in diabetic nephropathy.
Piglets	CP-Zn (5-10% zinc and 50-60% chitosan)	CP-Zn increased the activity of carbohydrate digestion-related enzymes and mRNA expression.	Zhang et al. (2021)ZHANG, M., HOU, G., HU, P., FENG, D., WANG, J. and ZHU, W., 2021. Nano chitosan-zinc complex improves the growth performance and antioxidant capacity of the small intestine in weaned piglets. British Journal of Nutrition, vol. 126, no. 6, pp. 801-812. http://dx.doi.org/10.1017/S0007114520004766. PMid:33256856. http://dx.doi.org/10.1017/S0007114520004...
Piglets	CP-Zn (5-10% zinc and 50-60% chitosan)	CP-Zn improved the antioxidant capacity of the jejunum by activating the Nrf2 signaling pathway.

Study Mode	Additive/dose	Findings	References
Rats	chitosan trimer (2.14 mg/kg)	Chitosan reduced blood pressure in spontaneously hypertensive rat models	Hong et al. (1998)HONG, S.P., KIM, M.H., OH, S.W., HAN, C.K. and KIM, Y.H., 1998. ACE inhibitory and antihypertensive effect of chitosan oligosaccharides in SHR. Korean Journal of Food Science Technology, vol. 30, no. 6, pp. 1476-1479.
In vitro	COSs with different MW and DD	The DD value and MW of COSs are important factors affecting renin-inhibitory activity.	Park et al. (2008)PARK, P.J., AHN, C.B., JEON, Y.J. and JE, J.Y., 2008. Renin inhibition activity by chitooligosaccharides. Bioorganic & Medicinal Chemistry Letters, vol. 18, no. 7, pp. 2471-2474. http://dx.doi.org/10.1016/j.bmcl.2008.02.041. PMid:18313296. http://dx.doi.org/10.1016/j.bmcl.2008.02...
Mice	COS	Chitosan might ameliorate endothelial dysfunction and exhibit an anti-hypertensive effect.	Li et al. (2014)LI, Y., LIU, H., XU, Q.S., DU, Y.G. and XU, J., 2014. Chitosan oligosaccharides block LPS-induced O-GlcNAcylation of NF-κB and endothelial inflammatory response. Carbohydrate Polymers, vol. 99, pp. 568-578. http://dx.doi.org/10.1016/j.carbpol.2013.08.082. PMid:24274545. http://dx.doi.org/10.1016/j.carbpol.2013...
Rats	5% high-MW chitosan	Used as pharmacotherapies or as a dietary fiber against hypertension, dyslipidemia, and obesity	Chiu et al. (2017)CHIU, C.Y., CHANG, T.C., LIU, S.H. and CHIANG, M.T., 2017. The regulatory effects of fish oil and chitosan on hepatic lipogenic signals in high-fat diet-induced obese rats. Yao Wu Shi Pin Fen Xi, vol. 25, no. 4, pp. 919-930. http://dx.doi.org/10.1016/j.jfda.2016.11.015. PMid:28987369. http://dx.doi.org/10.1016/j.jfda.2016.11...
Mice	chitosan oligosaccharide	Chitosan has useful effects on various components of metabolic syndrome, including obesity, dyslipidemia, diabetes mellitus, hyperglycemia, and hypertension.	Tao et al. (2021)TAO, W., WANG, G. and WEI, J., 2021. The role of chitosan oligosaccharide in metabolic syndrome: a review of possible mechanisms. Marine Drugs, vol. 19, no. 9, pp. 501. http://dx.doi.org/10.3390/md19090501. PMid:34564163. http://dx.doi.org/10.3390/md19090501...
Rats	Lecithin/CHNPs loaded with HCT	NPs increased the onset and duration of antihypertensive activity in DOCA-salt-induced hypertensive rats conclusively demonstrating the improved therapeutic efficacy of HCT when formulated as NPs.	Chadha et al. (2012)CHADHA, R., BHANDARI, S., KATARIA, D., GUPTA, S. and SINGH JAIN, D., 2012. Exploring the potential of lecithin/chitosan nanoparticles in enhancement of antihypertensive efficacy of hydrochlorothiazide. Journal of Microencapsulation, vol. 29, no. 8, pp. 805-812. http://dx.doi.org/10.3109/02652048.2012.692399. PMid:22681125. http://dx.doi.org/10.3109/02652048.2012....
Mice	CHNPs Loading Nifedipine	The polylactic acid/CHNPs loading nifedipine is suitable to apply in the treatment of hypertension.	Chinh et al. (2018)CHINH, N.T., TRANG, N.T.T., MAI, T.T., THANH, D.T.M., TRUNG, T.H., TRUNG, T.H., QUAN, L.V., HOA, N.T., MAO, C.V., NGHIA, N.T., HAI, N.T., ANH, T.H., HUNG, T.V., CHOY, J.H., LOI, N.V., RAJESH, B. and HOANG, T., 2018. Polylactic acid/chitosan nanoparticles loading Nifedipine: characterization findings and in vivo investigation in animal. Journal of Nanoscience and Nanotechnology, vol. 18, no. 4, pp. 2294-2303. http://dx.doi.org/10.1166/jnn.2018.14537. PMid:29442895. http://dx.doi.org/10.1166/jnn.2018.14537...
Rats	CHNPs fabricated by ionotropic gelation	The ACE-inhibitory biopeptides stabilized by chitosan nanoparticles can effectively reduce blood pressure for an extended period in hypertensive.	Auwal et al. (2017)AUWAL, S.M., ZAREI, M., TAN, C.P., BASRI, M. and SAARI, N., 2017. Improved in vivo efficacy of anti-hypertensive biopeptides encapsulated in chitosan nanoparticles fabricated by ionotropic gelation on spontaneously hypertensive rats. Nanomaterials, vol. 7, no. 12, pp. 421. http://dx.doi.org/10.3390/nano7120421. PMid:29207480. http://dx.doi.org/10.3390/nano7120421...
In vitro	Captopril loaded CHNPs	Reported antihypertensive nano-cuticles based on chitosan improved the oral administration of currently available hydrophobic drugs while providing an extended-release function.	Niaz et al. (2016)NIAZ, T., SHABBIR, S., MANZOOR, S., REHMAN, A., RAHMAN, A., NASIR, H. and IMRAN, M., 2016. Antihypertensive nano-ceuticales based on chitosan biopolymer: physico-chemical evaluation and release kinetics. Carbohydrate Polymers, vol. 142, pp. 268-274. http://dx.doi.org/10.1016/j.carbpol.2016.01.047. PMid:26917399. http://dx.doi.org/10.1016/j.carbpol.2016...
	SBs loaded Chitosan	The nanoparticles revealed sustained cumulative release for 12 h and improved efficacy with ACE-inhibitory.	Auwal et al. (2018)AUWAL, S.M., ZAREI, M., TAN, C.P., BASRI, M. and SAARI, N., 2018. Enhanced physicochemical stability and efficacy of angiotensin I-converting enzyme (ACE) - inhibitory biopeptides by chitosan nanoparticles optimized using Box-Behnken design. Scientific Reports, vol. 8, no. 1, pp. 10411. http://dx.doi.org/10.1038/s41598-018-28659-5. PMid:29991723. http://dx.doi.org/10.1038/s41598-018-286...
Humans In vitro	Nebivolol loaded CHNPs	Chitosan nanoparticles enhanced the oral bioavailability of nebivolol and other lipophilic drugs.	Sharma et al. (2018)SHARMA, M., SHARMA, R. and JAIN, D.K., 2018. Preparation, characterization and evaluation of nebivolol loaded chitosan nanoparticles. Journal of Drug Delivery and Therapeutics, vol. 8, no. 2, pp. 118-122. http://dx.doi.org/10.22270/jddt.v8i2.1730. http://dx.doi.org/10.22270/jddt.v8i2.173...

[1] *e-mail: dr.mohamed.e.abdalhaq@gmail.com

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Impactos da quitosana e suas nanoformulações nas síndromes metabólicas: uma revisão

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