Nanoparticle-based focused drug supply system for remedy of weight problems and atherosclerosis


Nanoparticle-based targeted drug delivery system for treatment of obesity and atherosclerosis
Development and analysis of liposomal nanoparticles for adipose-selective drug supply. a Schematic diagram of the construction of triiodothyronine (T3)-encapsulated PTP-modified liposomes (PLT3), which consists of HSPC, ldl cholesterol, DSPE-PEG2K, DSPE-PEG5K-PTP, in addition to T3. Cyanine 5 (Cy5) was encapsulated within the liposomes to hint the distribution of liposomes in vivo. b, c 8-week-old male C57BL/6 N mice have been injected intraperitoneally (IP) with free Cy5 (FCy5), Cy5-encapsulated unmodified liposomes (LCy5), or Cy5-encapsulated liposomes modified with totally different molar ratios of PTP (PLCy5s) and sacrificed 8 h after injection. b Relative fluorescence intensities in inguinal white adipose tissue (iWAT), epididymal white adipose tissue (eWAT), interscapular brown adipose tissue (iBAT), liver, spleen, coronary heart, lung, kidney, mind, and soleus have been decided by a fluorimeter. c Ex vivo fluorescence imaging evaluation for various tissues. d Fold adjustments of T3 focus relative to saline-treated controls in numerous tissues of 8-week-old male C57BL/6 N mice have been measured at 8 h after injection with FT3, LT3, PLT3, or saline. b–d n = 5 biologically unbiased replicates from one experiment. All information are expressed as imply ± SEM. One-way ANOVA adopted by Least Vital Distinction (LSD) take a look at was utilized for comparisons amongst a number of teams. Credit score: Nature Communications (2022). DOI: 10.1038/s41467-022-35470-4

A analysis staff from LKS College of Medication, the College of Hong Kong (HKUMed) has developed thyroid hormone (TH)–encapsulated nanoparticles modified with an adipose-homing peptide, which selectively transports TH to adipose tissues. It will advance the remedy of obesity-related medical issues with TH by overcoming the extreme opposed results attributable to systemic administration. The brand new findings are actually revealed in Nature Communications.

Weight problems is a serious threat issue for a number of life-threatening reminiscent of diabetes and cardiovascular and neurodegenerative problems. TH is an historic hormone with therapeutic potential for weight problems and its associated medical issues by selling power expenditure. Nonetheless, regardless of monumental analysis efforts previously many years, have didn’t display apparent scientific advantages of continual systemic administration of TH on in overweight people.

Moreover, as a consequence of widespread expression of TH receptors, systemic administration of TH typically results in critical deleterious results on a number of organs, together with tachycardia, , muscle losing, and osteoporosis. Skeletal muscle and adipose tissues are considered the 2 main goal organs the place TH exerts its stimulatory actions on metabolic fee and power expenditure. Nonetheless, whether or not selective supply of TH to adipose tissues is enough to induce weight reduction stays unclear.

The analysis staff developed TH-encapsulated nanoparticles, modified with an adipose-homing peptide to selectively ship TH to adipose tissues. Remarkably, the researchers discovered that adipose-targeted supply of TH is considerably stronger than systemic TH remedy in lowering weight problems and its associated metabolic issues, with no opposed impact on different non-adipose tissues.

Mechanistically, the examine uncovered that adipose-targeted TH remedy can convert “dangerous” white fats to “good” brown fats, which might burn energy by creating warmth, whereas systemic TH remedy is unable to induce “browning” of white fats as a consequence of its suppression of sympathetic nerves. Moreover, the analysis staff made an surprising discovering that adipose-targeted supply of TH successfully alleviates hypercholesterolemia and atherosclerosis, main causes of coronary coronary heart illness and ischemic stroke.

“That is the primary proof-of-concept examine displaying that nanoparticle-based focused supply of TH to adipose tissue is an efficient and secure pharmacotherapy for weight problems and its associated cardiometabolic issues. The findings have additionally resolved a long-standing thriller of why systemic TH remedy failed to cut back , thus reigniting the hope of utilizing this historic hormone for remedy of frequent continual illnesses by means of nanoparticle-based precision goal supply,” mentioned Professor Xu Aimin, Director of State Key Laboratory of Pharmaceutical Biotechnology and Professor of Division of Medication, Faculty of Medical Medication, HKUMed.

Extra data:
Kang Chen et al, Adipose-targeted triiodothyronine remedy counteracts obesity-related metabolic issues and atherosclerosis with negligible uncomfortable side effects, Nature Communications (2022). DOI: 10.1038/s41467-022-35470-4

Nanoparticle-based focused drug supply system for remedy of weight problems and atherosclerosis (2023, February 17)
retrieved 17 February 2023

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