ArticleJournal of controlled release : official journal of the Controlled Release Society2014
Pluronic modified leptin with increased systemic circulation, brain uptake and efficacy for treatment of obesity.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
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- Recent advances in potential drug nanocarriers for CNS disorders: a review.Biomedical engineering online · 2025Review
- Whispering Through the Barrier: Signaling Interfaces for Peripheral Regulation of Brain Function in Obesity.Journal of neurochemistry · 2025Review
- Anti-Obesity Drug Delivery Systems: Recent Progress and Challenges.Pharmaceutics · 2023Review
- Inverse association between blood ethylene oxide levels and obesity in the general population: NHANES 2013-2016.Frontiers in endocrinology · 2022Article
- Drug reformulation for a neglected disease. The NANOHAT project to develop a safer more effective sleeping sickness drug.PLoS neglected tropical diseases · 2021Article
- Polymeric Carriers for Controlled Drug Delivery in Obesity Treatment.Trends in endocrinology and metabolism: TEM · 2019Review
- Review
- Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis.Nature communications · 2019Article
- Drug Delivery Strategies for the Treatment of Metabolic Diseases.Advanced healthcare materials · 2019Review
- Intranasal Leptin Relieves Sleep-disordered Breathing in Mice with Diet-induced Obesity.American journal of respiratory and critical care medicine · 2019Article
- Intranasal delivery of N-terminal modified leptin-pluronic conjugate for treatment of obesity.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain.Biomaterials · 2017Article
- Blood-Brain Barriers in Obesity.The AAPS journal · 2017Review
- Article
- Brain signaling systems in the Type 2 diabetes and metabolic syndrome: promising target to treat and prevent these diseases.Future science OA · 2015Review
- Leptin applications in 2015: what have we learned about leptin and obesity?Current opinion in endocrinology, diabetes, and obesity · 2015Review
- Agile delivery of protein therapeutics to CNS.Journal of controlled release : official journal of the Controlled Release Society · 2014Review
- New pharmacological perspectives for the leptin receptor in the treatment of obesity.Frontiers in endocrinology · 2014Review
- Nano-particle delivery of brain derived neurotrophic factor after focal cerebral ischemia reduces tissue injury and enhances behavioral recovery.Pharmacology, biochemistry, and behaviorArticle
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Modification of hydrophilic proteins with amphiphilic block copolymers capable of crossing cell membranes is a new strategy to improve protein delivery to the brain. Leptin, a candidate for the treatment of epidemic obesity, has failed in part because of impairment in its transport across the blood-brain barrier (BBB) that develops with obesity. We posit that modification of leptin with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Pluronic P85 (P85) might permit this protein to penetrate the BBB independently of its transporter, thereby overcoming peripheral leptin resistance. Here we report that peripherally administered leptin-P85 conjugates exhibit biological activity by reducing food intake in mouse models of obesity (ob/ob, and diet-induced obese mouse). We further generated two new leptin-P85 conjugates: one, Lep(ss)-P85(L), containing one P85 chain and another, Lep(ss)-P85(H), containing multiple P85 chains. We report data on their purification, analytical characterization, peripheral and brain pharmacokinetics (PK). Lep(ss)-P85(L) crosses the BBB using the leptin transporter, and exhibits improved peripheral PK along with increased accumulation in the brain compared to unmodified leptin. Lep(ss)-P85(H) also has improved peripheral PK but in a striking difference to the first conjugate penetrates the BBB independently of the leptin transporter via a non-saturable mechanism. The results demonstrate that leptin analogs can be developed through chemical modification of the native leptin with P85 to overcome leptin resistance at the level of the BBB, thus improving the potential for the treatment of obesity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.