ABSTRACT
The accumulation of hyperphosphorylated tau protein aggregates is a key pathogenic event in Alzheimer's disease (AD) and induces mitochondrial dysfunction and reactive oxygen species overproduction. However, the treatment of AD remains challenging owning to the hindrance caused by the blood-brain barrier (BBB) and the complex pathology of AD. Nasal delivery represents an effective means of circumventing the BBB and delivering drugs to the brain. In this study, black phosphorus (BP) is used as a drug carrier, as well as an antioxidant, and loaded with a tau aggregation inhibitor, methylene blue (MB), to obtain BP-MB. For intranasal (IN) delivery, a thermosensitive hydrogel is fabricated by cross-linking carboxymethyl chitosan and aldehyde Pluronic F127 (F127-CHO) micelles. The BP-MB nanocomposite is incorporated into the hydrogel to obtain BP-MB@Gel. BP-MB@Gel could be injected intranasally, providing high nasal mucosal retention and controlled drug release. After IN administration, BP-MB is continuously released and delivered to the brain, exerting synergistic therapeutic effects by suppressing tau neuropathology, restoring mitochondrial function, and alleviating neuroinflammation, thus inducing cognitive improvements in mouse models of AD. These findings highlight a potential strategy for brain-targeted drug delivery in the management of the complex pathologies of AD.
Subject(s)
Administration, Intranasal , Alzheimer Disease , Chitosan , Cognitive Dysfunction , Hydrogels , Methylene Blue , Methylene Blue/chemistry , Methylene Blue/therapeutic use , Methylene Blue/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Animals , Mice , Hydrogels/chemistry , Chitosan/chemistry , Chitosan/analogs & derivatives , Cognitive Dysfunction/drug therapy , Poloxamer/chemistry , Drug Carriers/chemistry , Brain/metabolism , Brain/drug effects , Brain/pathology , Micelles , tau Proteins/metabolism , Disease Models, Animal , Drug Liberation , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Nanocomposites/chemistry , Nanocomposites/therapeutic use , Mitochondria/metabolism , Mitochondria/drug effectsABSTRACT
Today, about 50% of men and 15-30% of women are estimated to face hair-related problems, which create a significant psychological burden. Conventional treatments, including drug therapy and transplantation, remain the main strategies for the clinical management of these problems. However, these treatments are hindered by challenges such as drug-induced adverse effects and poor drug penetration due to the skin's barrier. Therefore, various efforts have been undertaken to enhance drug permeation based on the mechanisms of hair regrowth. Notably, understanding the delivery and diffusion of topically administered drugs is essential in hair loss research. This review focuses on the advancement of transdermal strategies for hair regrowth, particularly those involving external stimulation and regeneration (topical administration) as well as microneedles (transdermal delivery). Furthermore, it also describes the natural products that have become alternative agents to prevent hair loss. In addition, given that skin visualization is necessary for hair regrowth as it provides information on drug localization within the skin's structure, this review also discusses skin visualization strategies. Finally, it details the relevant patents and clinical trials in these areas. Together, this review highlights the innovative strategies for skin visualization and hair regrowth, aiming to provide novel ideas to researchers studying hair regrowth in the future.
ABSTRACT
The treatment of diabetic wounds remains challenging due to the excess levels of oxidative stress, vulnerability to bacterial infection, and persistent inflammation response during healing. The development of hydrogel wound dressings with ideal anti-inflammation, antioxidant, and anti-infective properties is an urgent clinical requirement. In the present study, an injectable thermosensitive niobium carbide (Nb2 C)-based hydrogel (Nb2 C@Gel) with antioxidative and antimicrobial activity is developed to promote diabetic wound healing. The Nb2 C@Gel system is composed of Nb2 C and a PLGA-PEG-PLGA triblock copolymer. The fabricated Nb2 C nanosheets (NSs) show good biocompatibility during in vitro cytotoxicity and hemocompatibility assays and in vivo toxicity assays. In vitro experiments show that Nb2 C NSs can efficiently eliminate reactive oxygen species (ROS), thus protecting cells in the wound from oxidative stress damage. Meanwhile, Nb2 C NSs also exhibit good near-infrared (NIR) photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli. In vivo results demonstrate that Nb2 C@Gel promotes wound healing by attenuating ROS levels, reducing oxidative damage, eradicating bacterial infection under NIR irradiation, and accelerating angiogenesis. To summarize, the Nb2 C@Gel system, with its ROS-scavenging, photothermal antimicrobial and hemostatic activities, can be a promising and effective strategy for the treatment of diabetic wounds.
Subject(s)
Bacterial Infections , Diabetes Mellitus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Antioxidants , Escherichia coli , Humans , Hydrogels , Niobium , Reactive Oxygen Species , Wound HealingABSTRACT
Parkinson's disease (PD), a neurodegenerative disease that shows a high incidence in older individuals, is becoming increasingly prevalent. Unfortunately, there is no clinical cure for PD, and novel anti-PD drugs are therefore urgently required. However, the selective permeability of the blood-brain barrier (BBB) poses a huge challenge in the development of such drugs. Fortunately, through strategies based on the physiological characteristics of the BBB and other modifications, including enhancement of BBB permeability, nanotechnology can offer a solution to this problem and facilitate drug delivery across the BBB. Although nanomaterials are often used as carriers for PD treatment, their biological activity is ignored. Several studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio effects. In this review, we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD treatment. Subsequently, we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological effects. Finally, we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this field. Our review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.
