scholarly journals Berberine-Loaded Biomimetic Nanoparticles Attenuate Inflammation of Experimental Allergic Asthma via Enhancing IL-12 Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Jin ◽  
Jiale Li ◽  
Miaoyuan Zhang ◽  
Renxing Luo ◽  
Peishan Lu ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Targeted Delivery ◽  
Lung Inflammation ◽  
Water Solubility ◽  
Inflammatory Cells ◽  
Water Soluble ◽  
Water Soluble Drugs ◽  
Biomimetic Nanoparticles ◽  
Experimental Allergic

Asthma is one of the most common chronic pulmonary disorders, affecting more than 330 million people worldwide. Unfortunately, there are still no specific treatments for asthma so far. Therefore, it is very important to develop effective therapeutics and medicines to deal with this intractable disease. Berberine (Ber) has fabulous anti-inflammatory and antibacterial effects, while its low water solubility and bioavailability greatly limit its curative efficiency. To improve the nasal mucosa absorption of poorly water-soluble drugs, such as Ber, we developed a platelet membrane- (PM-) coated nanoparticle (NP) system (PM@Ber-NPs) for targeted delivery of berberine to the inflammatory lungs. In vivo, PM@Ber-NPs exhibited enhanced targeting retention in the inflammatory lungs compared with free Ber. In a mouse model of house dust mite- (HDM-) induced asthma, PM@Ber-NPs markedly inhibited lung inflammation, as evident by reduced inflammatory cells and inflammatory cytokines in the lung compared with free Ber. Collectively, our study demonstrated the inhibitory actions of nasally delivered nanomedicines on HDM-induced asthma, primarily through regulating Th1/Th2 balance by enhancing IL-12 expression which could potentially reduce lung inflammation and allergic asthma.

scholarly journals Antifungal Activity of Novel Formulations Based on Terpenoid Prodrugs against C. albicans in a Mouse Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 633
Author(s):  
Suvidha Menon ◽  
Xiuyi Liang ◽  
Richa Vartak ◽  
Ketankumar Patel ◽  
Antonio Di Stefano ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Mouse Model ◽  
Water Solubility ◽  
Water Soluble ◽  
Water Soluble Drugs ◽  
Resistant Strains ◽  
Antimicrobial And Antifungal Activity ◽  
In Vitro Data

Carvacrol (CAR), a phenolic monoterpenoid, has been extensively investigated for its antimicrobial and antifungal activity. As a result of its poor physicochemical properties, water soluble carvacrol prodrugs (WSCPs) with improved water solubility were previously synthesized and found to possess antimicrobial activity. Here, three novel CAR analogs, WSCP1, WSCP2, and WSCP3, were tested against fluconazole (FLU)-sensitive and -resistant strains where they showed greater antifungal activity than CAR against C. albicans. The probable mechanism by which the CAR prodrugs exert the antifungal activity was studied. Results from medium acidification assays demonstrated that the CAR and its synthetically designed prodrugs inhibit the yeast plasma membrane H+-ATPase (Pma1p), an essential target in fungi. In other words, in vitro data indicated that CAR analogs can prove to be a better alternative to CAR considering their improved water solubility. In addition, CAR and WSCP1 were developed into intravaginal formulations and administered at test doses of 50 mg/kg in a mouse model of vulvovaginal candidiasis (VVC). Whereas the CAR and WSCP1 formulations both exhibited antifungal efficacy in the mouse model of VVC, the WSCP1 formulation was superior to CAR, showing a remarkable decrease in infection by ~120-fold compared to the control (infected, untreated animals). Taken together, a synthetically designed prodrug of CAR, namely WSCP1, proved to be a possible solution for poorly water-soluble drugs, an inhibitor of an essential yeast pump in vitro and an effective and promising antifungal agent in vivo.

scholarly journals Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 199 ◽  
Author(s):  
Chang Kim ◽  
Si Sung ◽  
Eun Lee ◽  
Tae Kang ◽  
Ho Yoon ◽  
...  
Keyword(s):  
Drug Loading ◽  
Mononuclear Phagocyte ◽  
Nanostructured Lipid Carriers ◽  
Water Soluble ◽  
Zeta Potentials ◽  
Grafting Ratio ◽  
Macrophage Phagocytosis ◽  
Water Soluble Drugs ◽  
High Payload

As a platform for hepsin-specific drug delivery, we previously prepared IPLVVPLRRRRRRRRC peptide (RIPL)-conjugated nanostructured lipid carriers (RIPL-NLCs) composed of Labrafil® M 1944 CS (liquid oil) and Precirol® ATO 5 (solid lipid). In this study, to prevent the recognition by the mononuclear phagocyte system, polyethylene glycol (PEG)-modified RIPL-NLCs (PEG-RIPL-NLCs) were prepared using PEG3000 at different grafting ratios (1, 5, and 10 mole %). All prepared NLCs showed a homogeneous dispersion (130–280 nm), with zeta potentials varying from −18 to 10 mV. Docetaxel (DTX) was successfully encapsulated in NLCs: encapsulation efficiency (93–95%); drug-loading capacity (102–109 µg/mg). PEG-RIPL-NLCs with a grafting ratio of 5% PEG or higher showed significantly reduced protein adsorption and macrophage phagocytosis. The uptake of PEG(5%)-RIPL-NLCs by cancer cell lines was somewhat lower than that of RIPL-NLCs because of the PEG-induced steric hindrance; however, the uptake level of PEG-RIPL-NLCs was still greater than that of plain NLCs. In vivo biodistribution was evaluated after tail vein injection of NLCs to normal mice. Compared to RIPL-NLCs, PEG(5%)-RIPL-NLCs showed lower accumulation in the liver, spleen, and lung. In conclusion, we found that PEG(5%)-RIPL-NLCs could be a promising nanocarrier for selective drug targeting with a high payload of poorly water-soluble drugs.

scholarly journals The Unique Protein-To-Protein Carotenoid Transfer Mechanism

2017 ◽  
Author(s):  
Eugene G. Maksimov ◽  
Nikolai N. Sluchanko ◽  
Yury B. Slonimskiy ◽  
Kirill S. Mironov ◽  
Konstantin E. Klementiev ◽  
...  
Keyword(s):  
Transfer Process ◽  
Targeted Delivery ◽  
Green Light ◽  
Water Soluble ◽  
Uncharacterized Protein ◽  
Water Soluble Protein ◽  
Orange Carotenoid Protein ◽  
Highly Hydrophobic

Orange Carotenoid Protein (OCP) is known to be an effector and regulator of cyanobacterial photoprotection. This 35 kDa water-soluble protein provides specific environment for keto-carotenoids, the excitation of which induced by the absorption of blue-green light causes dramatic but fully reversible rearrangements of the OCP structure, including carotenoid translocation and separation of C- and N-terminal domains upon transition from the basic orange to photoactivated red OCP form. While recent studies significantly improved our understanding of the OCP photocycle and interaction with phycobilisomes and the fluorescence recovery protein, the mechanism of OCP assembly remains unclear. Apparently, this process requires targeted delivery and incorporation of a highly hydrophobic carotenoid molecule into the water-soluble apoprotein of OCP. Recently, we introduced a novel carotenoid carrier protein, COCP, which consists of dimerized C-domain(s) of OCP and can combine with the isolated N-domain to form transient OCP-like species. Here, we demonstrate that in vitro COCP efficiently transfers otherwise tightly bound carotenoid to the full-length OCP apoprotein, resulting in formation of the photoactive OCP from completely photoinactive species. We accurately analyze peculiarities of this carotenoid transfer process which, to the best of our knowledge, seems unique, previously uncharacterized protein-to-protein carotenoid transfer process. We hypothesize that a similar OCP assembly can occur in vivo, substantiating specific roles of the COCP carotenoid carrier in cyanobacterial photoprotection.

scholarly journals Considerable Improvement of Ursolic Acid Water Solubility by Its Encapsulation in Dendrimer Nanoparticles: Design, Synthesis and Physicochemical Characterization

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2196 ◽  
Author(s):  
Silvana Alfei ◽  
Anna Maria Schito ◽  
Guendalina Zuccari
Keyword(s):  
Ursolic Acid ◽  
Water Solubility ◽  
Drug Loading ◽  
Physicochemical Characterization ◽  
Systemic Toxicity ◽  
Water Soluble ◽  
Design Synthesis ◽  
Pentacyclic Triterpenoid

Ursolic acid (UA) is a pentacyclic triterpenoid found in many medicinal plants and aromas endowed with numerous in vitro pharmacological activities, including antibacterial effects. Unfortunately, UA is poorly administered in vivo, due to its water insolubility, low bioavailability, and residual systemic toxicity, thus making urgent the development of water-soluble UA formulations. Dendrimers are nonpareil macromolecules possessing highly controlled size, shape, and architecture. In dendrimers with cationic surface, the contemporary presence of inner cavities and of hydrophilic peripheral functions, allows to encapsulate hydrophobic non-water-soluble drugs as UA, to enhance their water-solubility and stability, and to promote their protracted release, thus decreasing their systemic toxicity. In this paper, aiming at developing a new UA-based antibacterial agent administrable in vivo, we reported the physical entrapment of UA in a biodegradable not cytotoxic cationic dendrimer (G4K). UA-loaded dendrimer nanoparticles (UA-G4K) were obtained, which showed a drug loading (DL%) much higher than those previously reported, a protracted release profile governed by diffusion mechanisms, and no cytotoxicity. Also, UA-G4K was characterized by principal components analysis (PCA)-processed FTIR spectroscopy, by NMR and elemental analyses, and by dynamic light scattering experiments (DLS). The water solubility of UA-G4K was found to be 1868-fold times higher than that of pristine UA, thus making its clinical application feasible.

scholarly journals Albendazole solid dispersions against alveolar echinococcosis: a pharmacotechnical strategy to improve the efficacy of the drug

Parasitology ◽  
2020 ◽  
Vol 147 (9) ◽  
pp. 1026-1031
Author(s):  
Julia Fabbri ◽  
Patricia Eugenia Pensel ◽  
Clara María Albani ◽  
Lurdes Milagros Lopez ◽  
Analia Simonazzi ◽  
...  
Keyword(s):  
Alveolar Echinococcosis ◽  
Water Solubility ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Poloxamer 407 ◽  
Infection Model ◽  
Efficacy Study ◽  
Dissolution Profile ◽  
Germinal Layer

AbstractAlveolar echinococcosis is a neglected parasitic zoonosis caused by Echinococcus multilocularis. The pharmacological treatment is based on albendazole (ABZ). However, the low water solubility of the drug produces a limited dissolution rate, with the consequent failure in the treatment of the disease. Solid dispersions are a successful pharmacotechnical strategy to improve the dissolution profile of poorly water-soluble drugs. The aim of this work was to determine the in vivo efficacy of ABZ solid dispersions using poloxamer 407 as a carrier (ABZ:P407 solid dispersions (SDs)) in the murine intraperitoneal infection model for secondary alveolar echinococcosis. In the chemoprophylactic efficacy study, the ABZ suspension, the ABZ:P407 SDs and the physical mixture of ABZ and poloxamer 407 showed a tendency to decrease the development of murine cysts, causing damage to the germinal layer. In the clinical efficacy study, the ABZ:P407 SDs produced a significant decrease in the weight of murine cysts. In addition, the SDs produced extensive damage to the germinal layer. The increase in the efficacy of ABZ could be due to the improvement of water solubility and wettability of the drug due to the surfactant nature of poloxamer 407. In conclusion, this study is the basis for further research. This pharmacotechnical strategy might in the future offer novel treatment alternatives for human alveolar echinococcosis.

scholarly journals FORMULATION OF NANOPARTICLES OF TELMISARTAN INCORPORATED IN CARBOXYMETHYLCHITOSAN FOR THE BETTER DRUG DELIVERY AND ENHANCED BIOAVAILABILITY

2017 ◽  
Vol 10 (9) ◽  
pp. 236
Author(s):  
Upasana Yadav ◽  
Angshuman Ray Chowdhuri ◽  
Sumanta Kumar Sahu ◽  
Nuzhat Husain ◽  
Qamar Rehman
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Targeted Delivery ◽  
Drug Loading ◽  
Water Soluble ◽  
Bioavailability Enhancement ◽  
Water Soluble Drug ◽  
Efficient Option

  Objective: In this study, we have made an attempt to the developed formulation of nanoparticles (NPs) of telmisartan (TLM) incorporated in carboxymethyl chitosan (CMCS) for the better drug delivery and enhanced bioavailability.Materials and Methods: The NPs size and morphology were investigated by high-resolution transmission electron microscopy and field emission scanning electron microscopy, respectively. The crystal structures and surface functional groups were analyzed using X-ray diffraction pattern, and Fourier transform infrared spectroscopy, respectively.Results: To increase the solubility of TLM by targeted delivery of the drug through polymeric NPs is an alternative efficient, option for increasing the solubility. TLM nanosuspension powders were successfully formulated for dissolution and bioavailability enhancement of the drug. We focused on evaluating the influence of particle size and crystalline state on the in vitro and in vivo performance of TLM.Conclusion: In summary, we have developed a new approach toward the delivery of poorly water-soluble drug TLM by CMCS NPs. The particles having a good drug loading content and drug encapsulation efficiency. The cytotoxicity of the synthesized NPs is also very less.

scholarly journals Nanoparticle-Mediated Dual Targeting: An Approach for Enhanced Baicalin Delivery to the Liver

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 107 ◽  
Author(s):  
Iman Saad Ahmed ◽  
Hassan Medhat Rashed ◽  
Hend Fayez ◽  
Faten Farouk ◽  
Rehab Nabil Shamma
Keyword(s):  
Oral Administration ◽  
Water Solubility ◽  
Area Under The Curve ◽  
Oral Solution ◽  
Water Soluble ◽  
Spherical Particles ◽  
Therapeutic Molecules ◽  
Ph Dependent ◽  
Full Factorial

In this study, water-soluble chitosan lactate (CL) was reacted with lactobionic acid (LA), a disaccharide with remarkable affinity to hepatic asialoglycoprotein (ASGP) receptors, to form dual liver-targeting LA-modified-CL polymer for site-specific drug delivery to the liver. The synthesized polymer was used to encapsulate baicalin (BA), a promising bioactive flavonoid with pH-dependent solubility, into ultrahigh drug-loaded nanoparticles (NPs) via the ionic gelation method. The successful chemical conjugation of LA with CL was tested and the formulated drug-loaded LA-modified-CL-NPs were assessed in terms of particle size (PS), encapsulation efficiency (EE) and zeta potential (ZP) using full factorial design. The in vivo biodistribution and pharmacokinetics of the designed NPs were assessed using 99mTc-radiolabeled BA following oral administration to mice and results were compared to 99mTc-BA-loaded-LA-free-NPs and 99mTc-BA solution as controls. Results showed that the chemical modification of CL with LA was successfully achieved and the method of preparation of the optimized NPs was very efficient in encapsulating BA into nearly spherical particles with an extremely high EE exceeding 90%. The optimized BA-loaded-LA-modified-CL-NPs showed an average PS of 490 nm, EE of 93.7% and ZP of 48.1 mV. Oral administration of 99mTc-BA-loaded-LA-modified-CL-NPs showed a remarkable increase in BA delivery to the liver over 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA oral solution. The mean area under the curve (AUC0–24) estimates from liver data were determined to be 11-fold and 26-fold higher from 99mTc-BA-loaded-LA-modified-CL-NPs relative to 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA solution respectively. In conclusion, the outcome of this study highlights the great potential of using LA-modified-CL-NPs for the ultrahigh encapsulation of therapeutic molecules with pH-dependent/poor water-solubility and for targeting the liver.

Development and Characterization of the Neuroregenerative Xanthohumol C/Hydroxypropyl-β-cyclodextrin Complex Suitable for Parenteral Administration

Planta Medica ◽  
2019 ◽  
Vol 85 (16) ◽  
pp. 1233-1241
Author(s):  
Michael Kirchinger ◽  
Lara Bieler ◽  
Julia Tevini ◽  
Michael Vogl ◽  
Elisabeth Haschke-Becher ◽  
...  
Keyword(s):  
Water Solubility ◽  
Pharmaceutical Research ◽  
Water Soluble ◽  
Complexing Agents ◽  
Cyclodextrin Complex ◽  
Scanning Calorimetry ◽  
In Vivo Experiments ◽  
Strong Candidate

AbstractThe chroman-like chalcone Xanthohumol C, originally found in hops, was demonstrated to be a potent neuroregenerative and neuroprotective natural product and therefore constitutes a strong candidate for further pharmaceutical research. The bottleneck for in vivo experiments is the low water solubility of this chalcone. Consequently, we developed and validated a suitable formulation enabling in vivo administration. Cyclodextrins were used as water-soluble and nontoxic complexing agents, and the complex of Xanthohumol C and 2-hydroxypropyl-β-cyclodextrin was characterized using HPLC, HPLC-MS, NMR, and differential scanning calorimetry. The water solubility of Xanthohumol C increases with increasing concentrations of cyclodextrin. Using 50 mM 2-hydroxypropyl-β-cyclodextrin, solubility was increased 650-fold. Furthermore, in vitro bioactivity of Xanthohumol C in free and complexed form did not significantly differ, suggesting the release of Xanthohumol C from 2-hydroxypropyl-β-cyclodextrin. Finally, a small-scaled in vivo experiment in a rat model showed that after i. p. administration of the complex, Xanthohumol C can be detected in serum, the brain, and the cerebrospinal fluid at 1 and 6 h post-administration. Mean (± SD) Xanthohumol C serum concentrations after 1, 6, and 12 h were determined as 463.5 (± 120.9), 61.9 (± 13.4), and 9.3 (± 0.8) ng/mL upon i. v., and 294.3 (± 22.4), 45.5 (± 0.7), and 13 (± 1.0) ng/mL after i. p. application, respectively. Accordingly, the formulation of Xanthohumol C/2-hydroxypropyl-β-cyclodextrin is suitable for further in vivo experiments and further pharmaceutical research aiming for the determination of its neuroregenerative potential in animal disease models.

Exploration on the adsorption mechanism of aminopyrimidines and quinazoline compounds on graphene oxide: Hydrophobicity and structure-controlled release process

2019 ◽  
Vol 9 (5) ◽  
pp. 419-428
Author(s):  
Li Li ◽  
Chunjiao Pan ◽  
Zhongqiu Guo ◽  
Bingmi Liu ◽  
Hao Pan ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Computer Simulations ◽  
Water Solubility ◽  
High Water ◽  
Water Soluble ◽  
Release Process ◽  
Adsorption Mechanisms ◽  
Mechanical Stirring

In this study, graphene oxide was synthesized using the Hummers method, and stable and homogeneous graphene oxide aqueous solutions were obtained through mechanical stirring and ultrasonic stripping. In conjunction with our previous studies, graphene oxide-loaded insoluble compound delivery systems were prepared to verify the in vivo release profiles of the graphene oxide delivery system. Several insoluble compounds including imatinib, nilotinib, erlotinib, gefitinib, and afatinib were selected for loading and in vitro graphene oxide release assays to study the non-covalent adsorption mechanisms. Computer simulations were employed for validation processes. For in vivo release assays, the T1/2 values of the poorly water soluble groups were 1.104 ± 0.18 h and the Cmax was 2.600 ± 2.06 mg/L. In previous assays, compounds with high water solubility supported by graphene oxide were released and detected in vivo. The solubility of the compound and its binding force with the carrier played a crucial role in release. The results of graphene oxide loading experiments showed that the maximum loading and entrapment efficiencies of the insoluble model compounds with similar aromatic rings were comparable. Under basic conditions, the in vitro release rates and maximum release levels of amino pyrimidine were elevated. In contrast, quinazoline release declined. Combined with computer simulations, π–π stacking was identified as the dominant mechanism for adsorption onto graphene oxide. Both hydrogen bonding and cation-π bonds played an auxiliary reinforcing role, and the two were regarded as antagonistic.

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