Liposome BBB

Traumatic brain injury (TBI) effects both the brain and the immune system. Circulating monocytes/macrophages (Mo /Ma ) after a TBI may play an important role in preserving the blood-brain barrier (BBB), reducing brain edema, and interacting with resident microglia. To elucidate the role of circulating Mo /Ma , we utilized a monocyte/macrophage depletion model in response to TBI in male rats. Clodronate liposomes (CL) were used to deplete circulating Mo /Ma . A controlled cortical impact (CCI) injury model was used to create a TBI...

Liposomes (lip) carrying pharmaceuticals have shown promise in their ability to advance the therapy for neurodegenerative diseases. However, the low nerve-targeting capacity and poor penetration rate of lip through the blood-brain barrier (BBB) are major hurdles to achieving successful treatment. Herein, we developed lip incorporating cardiolipin (CL) and phosphatidic acid (PA) to promote their capability against hyperphosphorylation of tau protein, and a transactivator of transcription (TAT) peptide to permeate the BBB for delivering nerve growth factor (NGF), rosmarinic acid (RA), curcumin (CURC) and quercetin (QU)...

The blood-brain barrier (BBB) has long limited therapeutic access to brain tumor and peritumoral tissue. In animals, MR-guided focused ultrasound (MRgFUS) with intravenously injected microbubbles can temporarily and repeatedly disrupt the BBB in a targeted fashion, without open surgery. Our objective is to demonstrate safety and feasibility of MRgFUS BBB opening with systemically administered chemotherapy in patients with glioma in a phase I, single-arm, open-label study. Five patients with previously confirmed or suspected high-grade glioma based on imaging underwent the MRgFUS in conjunction with administration of chemotherapy (n = 1 liposomal doxorubicin, n = 4 temozolomide) one day prior to their scheduled surgical resection...

Effective therapy for Alzheimer's disease is a major challenge in the pharmaceutical sciences. There are six FDA approved drugs (e.g., donepezil, memantine) that show some effectiveness; however, they only relieve symptoms. Two factors hamper research. First, the cause of Alzheimer's disease is not fully understood. Second, the blood-brain barrier restricts drug efficacy. This review summarized current knowledge relevant to both of these factors. First, we reviewed the pathophysiology of Alzheimer's disease...

Transport of the majority of therapeutic molecules to the brain is precluded by the presence of the blood-brain barrier (BBB) rendering efficient treatment of many neurological disorders impossible. This BBB, nonetheless, may be circumvented by targeting receptors and transport proteins expressed on the luminal surface of the brain capillary endothelial cells (BCECs). The transferrin receptor (TfR) has remained a popular target since its original description for this purpose, although clinical progression of TfR-targeted drug constructs or nanomedicines remains unsuccessful...

The poor capability of drugs to permeate through blood brain barrier (BBB) and further release inside glioma greatly limit the curative effects of glioma chemotherapies. In this study, we prepared angiopep-2 conjugated liposome-silica hybrid nanovehicles for targeted delivery and increased the permeation of arsenic trioxide (ATO) in glioma. Polyacrylic acid (PAA) was grafted on mesoporous silica nanoparticles (MSN) for pH-sensitive release and supporting lipid membrane. The prepared "core-shell" nanovehicles (ANG-LP-PAA-MSN) were characterized with uniform size, high drug loading efficiency (8...

Gene therapy involving p11 cDNA has been thought to be a futuristic approach for the effective management of depression as the existing treatment regimen presents many issues regarding late onset of action, patient withdrawal and their side effects. For the effective transfection of p11 gene intracellularly, two cationic lipids based on phospholipid DOPE conjugated to basic amino acids histidine and arginine were synthesised, used for liposome formulation and evaluated for their ability as gene delivery vectors...

The treatment of glioma is a great challenge because of the existence of the blood-brain barrier (BBB). In order to develop an efficient glioma-targeting drug delivery system to greatly improve the brain permeability of anti-cancer drugs and target glioma, a novel glioma-targeted glucose-RGD (Glu-RGD) derivative was designed and synthesized as ligand for preparing liposomes to effectively deliver paclitaxel (PTX) to cross the BBB and target glioma. The liposomes were prepared and characterized for particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis, and cell cytotoxicity...

Malignant glioma is one of the most common and severe brain diseases, which is extremely hard to treat due to the presence of the blood-brain barrier (BBB). Ultrasound (US) triggered sonodynamic therapy (SDT) is rapidly emerging as a noninvasive cancer treatment which benefits from the deep penetration of ultrasound waves. It has been reported that US can reversibly open the BBB for the enhancement of drug delivery. Therefore, a few researchers have paid attention to sonodynamic therapy for the in situ treatment of gliomas...

BACKGROUND/AIM: Glioma is a deadly form of brain cancer. Doxorubicin is cytotoxic against glioma cells. However, the blood-brain barrier (BBB) limits its ability to be delivered to the brain. MATERIALS AND METHODS: Liposomes (R8PLP) formed from, 1,2-dioleoyl-3-trimethylammonium-propane chloride (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000] (PEG-DSPE), cholesterol and egg phosphatidylcholine (ePC) were modified by cell-penetrating peptide R8 conjugated with oleic acid as a novel method for delivering doxorubicin...

Alzheimer's disease (AD) will affect around 115 million people worldwide by the year 2050. It is associated with the accumulation of misfolded and aggregated proteins (β-amyloid and tau) in the senile plaques and neurofibrillary tangles found in the brain. Currently available drugs for AD only temporarily alleviate symptoms and do not slow the inevitable progression of this disease. New drugs are required that act on key pathologies in order to arrest or reverse cognitive decline. However, there has been a spectacular failure rate in clinical trials of conventional small molecule drugs or biological agents...

Orexin neurons originate in the lateral and dorsomedial hypothalamus and perifornical area and produce two different neuropeptides: orexin A (OxA) and orexin B (OxB), which activate OxR1 and OxR2 receptors. In the lateral hypothalamus (LH) orexin neurons are involved in behavior motivated by natural rewards such as palatable food (sugar, high-fat food) and it has been demonstrated similarly that the orexin signaling in the ventral tegmental area (VTA) is implicated in the intake of high-fat food. The VTA is an important area involved in reward processing...

The blood brain barrier (BBB) selectively controls the passage of endogenous and exogenous molecules between systemic circulation and the brain parenchyma. Nano-carrier based drugs such as liposomes and nanoparticles are an attractive prospect for cancer therapy since they can carry a drug payload and be modified to improve targeting and retention at the desired site. However, the BBB prevents most therapeutic drugs from entering the brain, including physically restricting the passage of liposomes and nanoparticles...

Resveratrol (RES) is a natural polyphenolic non-flavonoid compound present in grapes, mulberries, peanuts, rhubarb and in several other plants. Numerous health effects have been related with its intake, such as anti-carcinogenic, anti-inflammatory and brain protective effects. The neuroprotective effects of RES in neurological diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, are related to the protection of neurons against oxidative damage and toxicity, and to the prevention of apoptotic neuronal death...

Delivering therapeutics across the blood-brain barrier (BBB) for treating central nervous system (CNS) diseases is one of the biggest challenges today as the BBB limits the uptake of molecules greater than 500 Da into the CNS. Here we describe a novel trans-nasal mucosal drug delivery as an alternative to the intranasal drug delivery to overcome its limitations and deliver high molecular weight (HMW) therapeutics efficiently to the brain. This approach is based on human endoscopic skull base surgical techniques in which a surgical defect is repaired by engrafting semipermeable nasal mucosa over a skull base defect...

The major neurological disorders found in a central nervous system (CNS), such as brain tumors, Alzheimer's diseases, Parkinson's diseases, and Huntington's disease, have led to devastating outcomes on the human public health. Of these disorders, early diagnostics remains poor, and no treatment has been successfully discovered; therefore, they become the most life-threatening medical burdens worldwide compared to other major diseases. The major obstacles for the drug discovery are the presence of a restrictive blood-brain barrier (BBB), limiting drug entry into brains and undesired neuroimmune activities caused by untargeted drugs, leading to irreversible neuronal damages...

Epsilon toxin (Etx) from Clostridium perfringens is synthesized as a very low-active prototoxin form (proEtx) that becomes active upon proteolytic activation and has the capacity to cross the blood-brain barrier (BBB), thereby producing severe neurological effects. The identity and requirements of host receptors of Etx remain a matter of controversy. In the present study, we analysed the binding of proEtx or Etx to liposomes containing distearoylphosphatidylcholine (DSPC), cholesterol and sulfatide, or alternatively to detergent-solubilized lipids, using surface plasmon resonance (SPR)...

Despite the promising features of liposomes as brain drug delivery vehicles, it remains uncertain how they influence the brain uptake in vivo. In order to gain a better fundamental understanding of the interaction between liposomes and the blood-brain barrier (BBB), it is indispensable to test if liposomes affect drugs with different BBB transport properties (active influx or efflux) differently. The aim of this study was to quantitatively evaluate how PEGylated (PEG) liposomes influence brain delivery of diphenhydramine (DPH), a drug with active influx at the BBB, in rats...

The photodynamic (PD) effect has been reported to be efficient for the opening of the blood-brain barrier (BBB), which provides a new informative platform for developing perspective strategies towards brain disease therapy and drug delivery. However, this method is usually performed via craniotomy due to high scattering of the turbid skull. In this work, we employed a newly-developed optical clearing skull window for investigating non-invasive PD-induced BBB opening to high weight molecules and 100-nm fluid-phase liposomes containing ganglioside GM1...

Intranasal drug delivery is emerging as a reliable and promising pathway to deliver a wide range of therapeutic agents including small and large molecules, peptides and proteins, genes to the central nervous system for the treatment of brain diseases such as Alzheimer's disease, Parkinson's disease, depression, migraine, schizophrenia, and glioma. This presents noninvasive entry into the brain via direct nose-to-brain and/or indirect nose-to-blood-to-brain routes. Several nanocarrier-based strategies have been developed to transport therapeutic agents to the brain including nanoparticles, liposomes, and exosomes following intranasal delivery...