scholarly journals Smart niosomes of temozolomide for enhancement of brain targeting

2018 ◽  
Vol 5 ◽  
pp. 184954351880535 ◽  
Author(s):  
Anindita De ◽  
Nagasamy Venkatesh ◽  
M Senthil ◽  
Bharat Kumar Reddy Sanapalli ◽  
R Shanmugham ◽  
...  
Keyword(s):  
Alkylating Agent ◽  
Entrapment Efficiency ◽  
Optimum Concentration ◽  
Brain Targeting ◽  
Low Permeability ◽  
Target Area ◽  
Nanosized Particles ◽  
Amino Acid Peptide ◽  
Distribution Studies ◽  
The Brain

Drug delivery to the brain is challenging because of the low permeability of blood–brain barrier, and therefore, optimum concentration of chemotherapeutics in the target area specifically for glioblastoma, an aggressive brain tumor, opens a new path of research. To achieve the goal, the oral alkylating agent temozolomide was incorporated into niosomes, and the surface was modified with chlorotoxin, a small 36 amino acid peptide discovered from the venom of scorpion Leiurus quinquestriatus. Active targeting using nanosized particles facilitates an increase in the accumulation of drugs in the cerebri by 3.04-folds. Temozolomide-loaded niosomes were prepared using conventional thin-film hydration method and characterized. Niosomes coated with chlorotoxin were produced with the size of 220 ± 1.45 nm with an entrapment efficiency of 79.09 ± 1.56%. Quantitative tissue distribution studies indicate enhanced permeation of the drug into the brain because of surface modification with less deposition in the highly perfused organs.

scholarly journals ZOLMITRIPTAN BRAIN TARGETING VIA INTRANASAL ROUTE USING SOLID LIPID NANOPARTICLES FOR MIGRAINE THERAPY: FORMULATION, CHARACTERIZATION, IN-VITRO AND IN-VIVO ASSESSMENT

2020 ◽  
pp. 86-93 ◽  
Author(s):  
DALIA A. ELATY MOSTAFA ◽  
MAHA K. A. KHALIFA ◽  
SAMEH. S. GAD
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Solid Lipid Nanoparticles ◽  
Entrapment Efficiency ◽  
Lipid Nanoparticles ◽  
Brain Targeting ◽  
Histopathological Study ◽  
Solid Lipid ◽  
The Brain

Objective: Zolmitriptan, a class of antidepressant drugs with poor bioavailability due to its first-pass metabolism. The aim of this study was to improve systemic bioavailability and explore the brain targeting impact of nasal Zolmitriptan (Zol) solid lipid nanoparticles (SLNs) gel for migraine treatment.  Methods: Stearic acid and cholesterol used as solid lipid and lecithin as a surfactant, emulsion solvent evaporation technique was used to produce Zolmitriptan SLNs. (Zol) SLNs were characterized for particle size, percent entrapment efficiency and in vitro drug release. Formula S6 showed greater percent entrapment efficiency (PEE), adequate particle size and sustained drug release behavior. Formula S6 was integrated into HPMC gel (3%) to prepare nasal gel. Zol SLN nasal gel was subjected to histopathological study to ensure brain targeting.  Results: It was observed that all prepared Zol SLNs were in the nano-sized range with a polydispersity index of<0.5. In the cholesterol/lecithin combination, higher PEE%, better stability, and less agglomeration inclination were discovered. Results of the release profiles showed that developed Zol-SLNs were able to release Zolmitriptan in a sustained manner. Histopathological study of the brain tissues showed that Zolmitriptan SLN nasal gel can reach brain cells and localized for 24 h although the hydrophobicity of the target drug. Conclusion: Intranasal administration of Solid lipid nanostructure of Zolmitriptan through the olfactory pathway in which it travels from the nasal cavity to brain tissue achieved drug targeting potential of about 90% compared with conventional Zolmitriptan tablets. The small particle size helped them to squeeze themselves through the small opening in the olfactory neurons to the brain via different endo-cystic pathways of neuronal cells in nasal tissue membranes.

Immunoelectron microscope detection of C-type natriuretic peptide in normal human atrial tissue

1993 ◽  
Vol 51 ◽  
pp. 388-389
Author(s):  
Chi-Ming Wei ◽  
Margaret Hukee ◽  
Christopher G.A. McGregor ◽  
John C. Burnett
Keyword(s):  
Amino Acid ◽  
Natriuretic Peptide ◽  
Vascular Tone ◽  
Cardiac Tissue ◽  
Ring Structure ◽  
Terminal Amino Acid ◽  
Amino Acid Peptide ◽  
Normal Human ◽  
Terminal Amino ◽  
The Brain

C-type natriuretic peptide (CNP) is a newly identified peptide that is structurally related to atrial (ANP) and brain natriuretic peptide (BNP). CNP exists as a 22-amino acid peptide and like ANP and BNP has a 17-amino acid ring formed by a disulfide bond. Unlike these two previously identified cardiac peptides, CNP lacks the COOH-terminal amino acid extension from the ring structure. ANP, BNP and CNP decrease cardiac preload, but unlike ANP and BNP, CNP is not natriuretic. While ANP and BNP have been localized to the heart, recent investigations have failed to detect CNP mRNA in the myocardium although small concentrations of CNP are detectable in the porcine myocardium. While originally localized to the brain, recent investigations have localized CNP to endothelial cells consistent with a paracrine role for CNP in the control of vascular tone. While CNP has been detected in cardiac tissue by radioimmunoassay, no studies have demonstrated CNP localization in normal human heart by immunoelectron microscopy.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

scholarly journals Cardiac Targeting Peptide, a Novel Cardiac Vector: Studies in Bio-Distribution, Imaging Application, and Mechanism of Transduction

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 147 ◽  
Author(s):  
Maliha Zahid ◽  
Kyle Feldman ◽  
Gabriel Garcia-Borrero ◽  
Timothy Feinstein ◽  
Nicholas Pogodzinski ◽  
...  
Keyword(s):  
Computerized Tomography ◽  
Single Photon ◽  
Photon Emission ◽  
Induced Pluripotent Stem Cell ◽  
Transduction Efficiency ◽  
Extracellular Potassium ◽  
Extracellular Potassium Concentration ◽  
Amino Acid Peptide ◽  
Targeting Peptide ◽  
Distribution Studies

Our previous work identified a 12-amino acid peptide that targets the heart, termed cardiac targeting peptide (CTP). We now quantitatively assess the bio-distribution of CTP, show a clinical application with the imaging of the murine heart, and study its mechanisms of transduction. Bio-distribution studies of cyanine5.5-N-Hydroxysuccinimide (Cy5.5) labeled CTP were undertaken in wild-type mice. Cardiac targeting peptide was labeled with Technetium 99m (99mTc) using the chelator hydrazino-nicotinamide (HYNIC), and imaging performed using micro-single photon emission computerized tomography/computerized tomography (SPECT/CT). Human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMCs) were incubated with dual-labeled CTP, and imaged using confocal microscopy. TriCEPs technology was utilized to study the mechanism of transduction. Bio-distribution studies showed peak uptake of CTP at 15 min. 99mTc-HYNIC-CTP showed heart-specific uptake. Robust transduction of beating human iPSC-derived CMCs was seen. TriCEPs experiments revealed five candidate binding partners for CTP, with Kcnh5 being felt to be the most likely candidate as it showed a trend towards being competed out by siRNA knockdown. Transduction efficiency was enhanced by increasing extracellular potassium concentration, and with Quinidine, a Kcnh5 inhibitor, that blocks the channel in an open position. We demonstrate that CTP transduces the normal heart as early as 15 min. 99mTc-HYNIC-CTP targets the normal murine heart with substantially improved targeting compared with 99mTc Sestamibi. Cardiac targeting peptide’s transduction ability is not species limited and has human applicability. Cardiac targeting peptide appears to utilize Kcnh5 to gain cell entry, a phenomenon that is affected by pre-treatment with Quinidine and changes in potassium levels.

scholarly journals Preparation, characterization and scale-up of sesamol loaded solid lipid nanoparticles

2012 ◽  
Vol 2 (1) ◽  
pp. 8 ◽  
Author(s):  
Vandita Kakkar ◽  
Indu Pal Kaur
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Scale Up ◽  
Spherical Shape ◽  
Entrapment Efficiency ◽  
Lipid Nanoparticles ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Solid Lipid ◽  
Transmission Electron ◽  
The Brain

Sesamol loaded solid lipid nanoparticles (SSLNs) were prepared with the aim of minimizing its distribution to tissues and achieving its targeting to the brain. Three scale-up batches (100x1 L) of S-SLNs were prepared using a microemulsification technique and all parameters were statistically compared with the small batch (1x;10 mL). S-SLNs with a particle size of less than 106 nm with a spherical shape (transmission electron microscopy) were successfully prepared with a total drug content and entrapment efficiency of 94.26±2.71% and 72.57±5.20%, respectively. Differential scanning calorimetry and infrared spectroscopy confirmed the formation of lipidic nanoparticles while powder X-ray diffraction revealed their amorphous profile. S-SLNs were found to be stable for three months at 5±3°C in accordance with International Conference on Harmonisation guidelines. The SLN preparation process was successfully scaled-up to a 100x batch on a laboratory scale. The procedure was easy to perform and allowed reproducible SLN dispersions to be obtained.

DEVELOPMENT, CHARACTERIZATION AND BRAIN DISTRIBUTION STUDIES OF NANOSTRUCTURED LIPID CARRIER CONTAINING SAQUINAVIR MESYLATE FOR NASAL ADMINISTRATION

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (09) ◽  
pp. 38-47
Author(s):  
H. S. Mahajan ◽  
◽  
M. I. Patel
Keyword(s):  
Adverse Effect ◽  
Targeted Delivery ◽  
Entrapment Efficiency ◽  
Nasal Administration ◽  
Nanostructured Lipid Carrier ◽  
Brain Distribution ◽  
Scanning Calorimetry ◽  
Distribution Studies

The aim of the present study was to formulate saquinavir mesylate loaded nanostructured lipid carriers (SQVM-NLC) and evaluate its brain distribution after nasal administration. NLCs reveal some advantages for drug therapy over conventional carriers, including increased solubility, the ability to enhance storage stability, improved permeability and bioavailability, reduced adverse effect, prolonged half-life, and tissue-targeted delivery. SQVM-NLCs were prepared by hot high pressure homogenization and subsequent stabilization by lyophilization. QVM- NLC developed showed a particle with the size of 124.4 nm, polydispersity index of 0.267, entrapment efficiency of 73% and the zeta potential of -24.9 mV. The results from Scanning Electron Microscopy (SEM), powder X-ray diffraction (XRD)and differential scanning calorimetry (DSC) demonstrated that SQVM was present in NLC in an encapsulated molecule form. Mucosal toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVMloaded NLC. SQVM-NLC showed slower release compared with saquinavir mesylate suspension in vitro. In vivo brain distribution studies demonstrated desired drug concentration in brain after intra nasal administration of SQVM-NLC than PDS. The results of the study also suggest that SQVM-NLC could be a promising drug delivery system for antiretroviral therapy.

scholarly journals Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1059
Author(s):  
Saif Ahmad Khan ◽  
Saleha Rehman ◽  
Bushra Nabi ◽  
Ashif Iqubal ◽  
Nida Nehal ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Fold Increase ◽  
Pharmacokinetic Studies ◽  
Nanostructured Lipid Carrier ◽  
Brain Delivery ◽  
The Brain

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir.

scholarly journals Intranasal Nanoemulsions for Direct Nose-to-Brain Delivery of Actives for CNS Disorders

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1230
Author(s):  
Shiv Bahadur ◽  
Dinesh M. Pardhi ◽  
Jarkko Rautio ◽  
Jessica M. Rosenholm ◽  
Kamla Pathak
Keyword(s):  
Rapid Development ◽  
Brain Targeting ◽  
Nasal Administration ◽  
Future Research ◽  
Brain Delivery ◽  
Olfactory Pathway ◽  
Nasal Drug Delivery ◽  
Cns Diseases ◽  
Biodistribution Studies ◽  
The Brain

The treatment of various central nervous system (CNS) diseases has been challenging, despite the rapid development of several novel treatment approaches. The blood–brain barrier (BBB) is one of the major issues in the treatment of CNS diseases, having major role in the protection of the brain but simultaneously constituting the main limiting hurdle for drugs targeting the brain. Nasal drug delivery has gained significant interest for brain targeting over the past decades, wherein the drug is directly delivered to the brain by the trigeminal and olfactory pathway. Various novel and promising formulation approaches have been explored for drug targeting to the brain by nasal administration. Nanoemulsions have the potential to avoid problems, including low solubility, poor bioavailability, slow onset of action, and enzymatic degradation. The present review highlights research scenarios of nanoemulsions for nose-to-brain delivery for the management of CNS ailments classified on the basis of brain disorders and further identifies the areas that remain unexplored. The significance of the total dose delivered to the target region, biodistribution studies, and long-term toxicity studies have been identified as the key areas of future research.

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