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1.
Drug Deliv ; 28(1): 1281-1289, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34176374

ABSTRACT

Current treatments for osteoporosis and other bone degenerative diseases predominately rely on preventing further bone erosion rather than restoring bone mass, as the latter treatments can unintentionally trigger cancer development by undiscriminatingly promoting cell proliferation. One approach to circumvent this problem is through the development of novel chemical carriers to deliver drug agents specifically to bones. We have recently shown that carbon nanodots (C-dots) synthesized from carbon nanopowder can bind with high affinity and specificity to developing bones in the larval zebrafish. Larval bones, however, are physiologically different from adult bones in their growth, repair, and regeneration properties. Here we report that C-dots can bind to adult zebrafish bones and that this binding is highly specific to areas of appositional growth. C-dots deposition occurred within 30 minutes after delivery and was highly selective, with bones undergoing regeneration and repair showing higher levels of C-dots deposition than bones undergoing normal homeostatic turnover. Importantly, C-dots deposition did not interfere with bone regeneration or the animal's health. Together, our results establish C-dots as a potential novel vehicle for the targeted delivery of drugs to treat adult bone disease.


Subject(s)
Carbon/pharmacokinetics , Drug Carriers/pharmacokinetics , Nanoparticles/chemistry , Animals , Bone Regeneration/physiology , Bone and Bones/metabolism , Carbon/chemistry , Drug Carriers/chemistry , Zebrafish
2.
Nanoscale ; 9(44): 17533-17543, 2017 Nov 16.
Article in English | MEDLINE | ID: mdl-29110000

ABSTRACT

Bone-related diseases and dysfunctions are heavy burdens on our increasingly aged society. One important strategy to relieve this problem is through early detection and treatment of bone-related diseases. Towards this goal, there has been constant interest in developing novel bone-specific materials for imaging and drug delivery. Currently, however, materials that have high affinity and specificity towards bone are very limited. Carbon dots (C-dots) synthesized from carbon nanopowder bind to calcified bones in vivo with high affinity and specificity. In this study we show that bone binding is highly unique to a specific type of C-dot, and that this binding is non-toxic. Significantly, C-dots derived from other raw materials did not show any bone binding properties. These differences are attributed to the differences in surface chemistry of C-dot preparations, highlighting the heterogeneous nature of C-dots. Importantly, bone-binding by carbon nanopowder derived C-dots is not significantly altered by chemical functionalization of their surface. These unique properties indicate the potential applications of carbon nanopowder-derived C-dots as highly bone-specific bioimaging agents and drug carriers.


Subject(s)
Biocompatible Materials/chemistry , Bone and Bones/diagnostic imaging , Carbon/chemistry , Drug Carriers/chemistry , Quantum Dots , Animals , Embryo, Nonmammalian , Zebrafish
3.
Philos Trans R Soc Lond B Biol Sci ; 369(1645): 20130437, 2014.
Article in English | MEDLINE | ID: mdl-24821923

ABSTRACT

The global health community has set itself the task of eliminating tuberculosis (TB) as a public health problem by 2050. Although progress has been made in global TB control, the current decline in incidence of 2% yr(-1) is far from the rate needed to achieve this. If we are to succeed in this endeavour, new strategies to reduce the reservoir of latently infected persons (from which new cases arise) would be advantageous. However, ascertainment of the extent and risk posed by this group is poor. The current diagnostics tests (tuberculin skin test and interferon-gamma release assays) poorly predict who will develop active disease and the therapeutic options available are not optimal for the scale of the intervention that may be required. In this article, we outline a basis for our current understanding of latent TB and highlight areas where innovation leading to development of novel diagnostic tests, drug regimens and vaccines may assist progress. We argue that the pool of individuals at high risk of progression may be significantly smaller than the 2.33 billion thought to be immune sensitized by Mycobacterium tuberculosis and that identifying and targeting this group will be an important strategy in the road to elimination.


Subject(s)
Disease Eradication/methods , Global Health/trends , Latent Tuberculosis/diagnosis , Latent Tuberculosis/drug therapy , Latent Tuberculosis/epidemiology , Mycobacterium tuberculosis/physiology , Adaptation, Physiological/physiology , Disease Eradication/statistics & numerical data , History, 20th Century , History, 21st Century , Humans , Risk Factors , Tuberculin Test/history
4.
Eur J Intern Med ; 16(8): 603-5, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16314246

ABSTRACT

Botulinum toxin is now an important therapeutic agent in various clinical specialties. Although a lot is known about its short-term effects, little is known about the long-term effects or delayed complications. Most of the therapeutic effects appear within a week and last for 10-12 weeks. In most cases, the side effects are mild and often self-limiting and tend to occur within the first week. Myofascial necrosis and delayed onset of side effects are rarely reported and present a new challenge for a drug that has been proclaimed as an anti-ageing drug by the lay press and is widely used outside the licensed indications.

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