scholarly journals Improving the Utility of a Dynorphin Peptide Analogue Using Mannosylated Glycoliposomes

2021 ◽  
Vol 22 (15) ◽  
pp. 7996
Author(s):  
Jordan D. Lewicky ◽  
Nya L. Fraleigh ◽  
Alexandrine L. Martel ◽  
Thi M.-D. Nguyen ◽  
Peter W. Schiller ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Delivery Systems ◽  
Kappa Opioid Receptor ◽  
Antagonist Activity ◽  
Peptide Analogue ◽  
Nanoparticle Delivery ◽  
The Central Nervous System ◽  
Metabolic Degradation ◽  
Distribution Studies

Peptide therapeutics offer numerous advantages in the treatment of diseases and disorders of the central nervous system (CNS). However, they are not without limitations, especially in terms of their pharmacokinetics where their metabolic lability and low blood–brain barrier penetration hinder their application. Targeted nanoparticle delivery systems are being tapped for their ability to improve the delivery of therapeutics into the brain non-invasively. We have developed a family of mannosylated glycoliposome delivery systems for targeted drug delivery applications. Herein, we demonstrate via in vivo distribution studies the potential of these glycoliposomes to improve the utility of CNS active therapeutics using dynantin, a potent and selective dynorphin peptide analogue antagonist of the kappa opioid receptor (KOR). Glycoliposomal entrapment protected dynantin against known rapid metabolic degradation and ultimately improved brain levels of the peptide by approximately 3–3.5-fold. Moreover, we linked this improved brain delivery with improved KOR antagonist activity by way of an approximately 30–40% positive modulation of striatal dopamine levels 20 min after intranasal administration. Overall, the results clearly highlight the potential of our glycoliposomes as a targeted delivery system for therapeutic agents of the CNS.

scholarly journals Mechanisms and Pharmaceutical Action of Lipid Nanoformulation of Natural Bioactive Compounds as Efficient Delivery Systems in the Therapy of Osteoarthritis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1108
Author(s):  
Oana Craciunescu ◽  
Madalina Icriverzi ◽  
Paula Ecaterina Florian ◽  
Anca Roseanu ◽  
Mihaela Trif
Keyword(s):  
Drug Delivery ◽  
Bioactive Compounds ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Joint Disease ◽  
Duration Of Action ◽  
Immune System Activation

Osteoarthritis (OA) is a degenerative joint disease. An objective of the nanomedicine and drug delivery systems field is to design suitable pharmaceutical nanocarriers with controllable properties for drug delivery and site-specific targeting, in order to achieve greater efficacy and minimal toxicity, compared to the conventional drugs. The aim of this review is to present recent data on natural bioactive compounds with anti-inflammatory properties and efficacy in the treatment of OA, their formulation in lipid nanostructured carriers, mainly liposomes, as controlled release systems and the possibility to be intra-articularly (IA) administered. The literature regarding glycosaminoglycans, proteins, polyphenols and their ability to modify the cell response and mechanisms of action in different models of inflammation are reviewed. The advantages and limits of using lipid nanoformulations as drug delivery systems in OA treatment and the suitable route of administration are also discussed. Liposomes containing glycosaminoglycans presented good biocompatibility, lack of immune system activation, targeted delivery of bioactive compounds to the site of action, protection and efficiency of the encapsulated material, and prolonged duration of action, being highly recommended as controlled delivery systems in OA therapy through IA administration. Lipid nanoformulations of polyphenols were tested both in vivo and in vitro models that mimic OA conditions after IA or other routes of administration, recommending their clinical application.

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 Single-Walled Carbon Nanohorns as Promising Nanotube-Derived Delivery Systems to Treat Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 850 ◽  
Author(s):  
Alazne Moreno-Lanceta ◽  
Mireia Medrano-Bosch ◽  
Pedro Melgar-Lesmes
Keyword(s):  
Drug Delivery ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Physicochemical Characteristics ◽  
Delivery Systems ◽  
Preclinical Research ◽  
Carbon Nanohorns ◽  
Single Walled Carbon

Cancer has become one of the most prevalent diseases worldwide, with increasing incidence in recent years. Current pharmacological strategies are not tissue-specific therapies, which hampers their efficacy and results in toxicity in healthy organs. Carbon-based nanomaterials have emerged as promising nanoplatforms for the development of targeted delivery systems to treat diseased cells. Single-walled carbon nanohorns (SWCNH) are graphene-based horn-shaped nanostructure aggregates with a multitude of versatile features to be considered as suitable nanosystems for targeted drug delivery. They can be easily synthetized and functionalized to acquire the desired physicochemical characteristics, and no toxicological effects have been reported in vivo followed by their administration. This review focuses on the use of SWCNH as drug delivery systems for cancer therapy. Their main applications include their capacity to act as anticancer agents, their use as drug delivery systems for chemotherapeutics, photothermal and photodynamic therapy, gene therapy, and immunosensing. The structure, synthesis, and covalent and non-covalent functionalization of these nanoparticles is also discussed. Although SWCNH are in early preclinical research yet, these nanotube-derived nanostructures demonstrate an interesting versatility pointing them out as promising forthcoming drug delivery systems to target and treat cancer cells.

scholarly journals Fabrication and Characterization of Paclitaxel and Resveratrol Loaded Soluplus Polymeric Nanoparticles for Improved BBB Penetration for Glioma Management

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3210
Author(s):  
Talib Hussain ◽  
Sathishbabu Paranthaman ◽  
Syed Mohd Danish Rizvi ◽  
Afrasim Moin ◽  
Devegowda Vishakante Gowda ◽  
...  
Keyword(s):  
Polymeric Nanoparticles ◽  
C6 Glioma Cells ◽  
Brain Distribution ◽  
Distribution Study ◽  
Therapeutic Modalities ◽  
The Central Nervous System ◽  
Distribution Studies

Gliomas are one of the prominent cancers of the central nervous system with limited therapeutic modalities. The present investigation evaluated the synergistic effect of paclitaxel (PAX) and resveratrol (RESV)-loaded Soluplus polymeric nanoparticles (PNPs) against glioma cell lines along with in vivo pharmacokinetics and brain distribution study. PAX-RESV-loaded PNPs were prepared by the thin film hydration technique and optimized for different dependent and independent variables by using DoE (Design-Expert) software. The in vitro physiochemical characterization of prepared PAX-RESV-loaded PNPs exhibited appropriate particle size, PDI and % encapsulation efficiency. Cytotoxicity assay revealed that PTX-RESV loaded PNPs had a synergistic antitumor efficacy against C6 glioma cells compared with single and combined pure drugs. Finally, the pharmacokinetic and brain distribution studies in mice demonstrated that the PNPs significantly enhanced the bioavailability of PTX-RESV PNPs than pure PAX and RESV. Thus, the study concluded that PAX-RESV PNPs combination could significantly enhance anti-glioma activity, and this could be developed into a potential glioma treatment strategy.

Gold Nanoparticles as Targeted Delivery Systems and Theranostic Agents in Cancer Therapy

2019 ◽  
Vol 26 (35) ◽  
pp. 6493-6513 ◽  
Author(s):  
Alexandra Mioc ◽  
Marius Mioc ◽  
Roxana Ghiulai ◽  
Mirela Voicu ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
In Vivo Studies ◽  
Theranostic Agents ◽  
Targeted Delivery Systems

Cancer is still a leading cause of death worldwide, while most chemotherapies induce nonselective toxicity and severe systemic side effects. To address these problems, targeted nanoscience is an emerging field that promises to benefit cancer patients. Gold nanoparticles are nowadays in the spotlight due to their many well-established advantages. Gold nanoparticles are easily synthesizable in various shapes and sizes by a continuously developing set of means, including chemical, physical or eco-friendly biological methods. This review presents gold nanoparticles as versatile therapeutic agents playing many roles, such as targeted delivery systems (anticancer agents, nucleic acids, biological proteins, vaccines), theranostics and agents in photothermal therapy. They have also been outlined to bring great contributions in the bioimaging field such as radiotherapy, magnetic resonance angiography and photoacoustic imaging. Nevertheless, gold nanoparticles are therapeutic agents demonstrating its in vitro anti-angiogenic, anti-proliferative and pro-apoptotic effects on various cell lines, such as human cervix, human breast, human lung, human prostate and murine melanoma cancer cells. In vivo studies have pointed out data regarding the bioaccumulation and cytotoxicity of gold nanoparticles, but it has been emphasized that size, dose, surface charge, sex and especially administration routes are very important variables.

scholarly journals Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia

Blood ◽  
2013 ◽  
Vol 121 (1) ◽  
pp. 136-147 ◽  
Author(s):  
Bo Yu ◽  
Yicheng Mao ◽  
Li-Yuan Bai ◽  
Sarah E. M. Herman ◽  
Xinmei Wang ◽  
...  
Keyword(s):  
B Cell ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Small Interfering Rnas ◽  
Nanoparticle Delivery ◽  
Enhanced Sensitivity ◽  
Efficient Gene

Abstract Several RNA-targeted therapeutics, including antisense oligonucleotides (ONs), small interfering RNAs, and miRNAs, constitute immunostimulatory CpG motifs as an integral part of their design. The limited success with free antisense ONs in hematologic malignancies in recent clinical trials has been attributed to the CpG motif–mediated, TLR-induced prosurvival effects and inefficient target modulation in desired cells. In an attempt to diminish their off-target prosurvival and proinflammatory effects and specific delivery, as a proof of principle, in the present study, we developed an Ab-targeted liposomal delivery strategy using a clinically relevant CD20 Ab (rituximab)–conjugated lipopolyplex nanoparticle (RIT-INP)– and Bcl-2–targeted antisense G3139 as archetypical antisense therapeutics. The adverse immunostimulatory responses were abrogated by selective B cell–targeted delivery and early endosomal compartmentalization of G3139-encapsulated RIT-INPs, resulting in reduced NF-κB activation, robust Bcl-2 down-regulation, and enhanced sensitivity to fludarabine-induced cytotoxicity. Furthermore, significant in vivo therapeutic efficacy was noted after RIT-INP–G3139 administration in a disseminated xenograft leukemia model. The results of the present study demonstrate that CD20-targeted delivery overcomes the immunostimulatory properties of CpG-containing ON therapeutics and improves efficient gene silencing and in vivo therapeutic efficacy for B-cell malignancies. The broader implications of similar approaches in overcoming immunostimulatory properties of RNA-directed therapeutics in hematologic malignancies are also discussed.

scholarly journals Targeted Delivery System of Nanobiomaterials in Anticancer Therapy: From Cells to Clinics

2014 ◽  
Vol 2014 ◽  
pp. 1-23 ◽  
Author(s):  
Su-Eon Jin ◽  
Hyo-Eon Jin ◽  
Soon-Sun Hong
Keyword(s):  
Anticancer Drugs ◽  
Targeted Delivery ◽  
Polymeric Nanoparticles ◽  
Anticancer Therapy ◽  
Delivery Systems ◽  
Specific Receptors ◽  
Targeted Delivery System ◽  
Targeted Delivery Systems

Targeted delivery systems of nanobiomaterials are necessary to be developed for the diagnosis and treatment of cancer. Nanobiomaterials can be engineered to recognize cancer-specific receptors at the cellular levels and to deliver anticancer drugs into the diseased sites. In particular, nanobiomaterial-based nanocarriers, so-called nanoplatforms, are the design of the targeted delivery systems such as liposomes, polymeric nanoparticles/micelles, nanoconjugates, norganic materials, carbon-based nanobiomaterials, and bioinspired phage system, which are based on the nanosize of 1–100 nm in diameter. In this review, the design and the application of these nanoplatforms are discussed at the cellular levels as well as in the clinics. We believe that this review can offer recent advances in the targeted delivery systems of nanobiomaterials regardingin vitroandin vivoapplications and the translation of nanobiomaterials to nanomedicine in anticancer therapy.

scholarly journals Nanotechnology in Neurology—Current Status and Future Possibilities

US Neurology ◽  
2010 ◽  
Vol 06 (01) ◽  
pp. 12 ◽  
Author(s):  
James M Provenzale ◽  
Aaron M Mohs ◽  
◽  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ex Vivo ◽  
Current Status ◽  
Medical Applications ◽  
Nanoparticle Delivery ◽  
New Methods ◽  
The Central Nervous System ◽  
Neuro Protection

The field of nanomedicine is rapidly emerging and will provide many novel methods for diagnosis and treatment. In this article the applications of nanotechnology to the central nervous system (CNS) will be described. Nanotechnology provides many potential solutions to various problems encountered in CNS diseases. Specifically, nanomedicine offers the possibility of new methods of drug delivery, more sensitive and specific means for diagnosis of disease at earlier stages and assessment of treatment response, and also potential techniques for neuro-protection and neuro-engineering. In this article, information is provided on the various types of nanoparticles involved in medical applications, the principles of nanoparticle delivery and targeting, and bothin vivoandex vivouses of nanoscale materials.

scholarly journals The kappa opioid receptor is associated with the perception of visceral pain

Gut ◽  
1998 ◽  
Vol 43 (3) ◽  
pp. 312-313 ◽  
Author(s):  
D BLACK ◽  
M TREVETHICK
Keyword(s):  
Opioid Receptor ◽  
Visceral Pain ◽  
Kappa Opioid Receptor ◽  
Morphine Analgesia ◽  
Kappa Opioid ◽  
Morphine Abstinence ◽  
The Central Nervous System ◽  
Behavioural Tests ◽  
Deficient Mice

μ-, δ- and κ-opioid receptors are widely expressed in the central nervous system where they mediate the strong analgesic and mood-altering actions of opioids, and modulate numerous endogenous functions. To investigate the contribution of the κ-opioid receptor (KOR) to opioid function in vivo, we have generated KOR-deficient mice by gene targeting. We show that absence of KOR does not modify expression of the other components of the opioid system, and behavioural tests indicate that spontaneous activity is not altered in mutant mice. The analysis of responses to various nociceptive stimuli suggests that theKOR gene product is implicated in the perception of visceral chemical pain. We further demonstrate that KOR is critical to mediate the hypolocomotor, analgesic and aversive actions of the prototypic κ-agonist U-50,488H. Finally, our results indicate that this receptor does not contribute to morphine analgesia and reward, but participates in the expression of morphine abstinence. Together, our data demonstrate that theKOR-encoded receptor plays a modulatory role in specific aspects of opioid function.

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