Physicochemical Characterization and Antitumor Activity of Water-Soluble Polysaccharides from Bupleurum chinense

Solid dispersions are one of the most promising strategies to improve the oral bioavailability of poorly water soluble drugs. By reducing drug particle size to the absolute minimum, and hence improving drug wettability, bioavailability may be significantly improved. This article reviews the various preparation techniques for solid dispersion and compiles some of the recent technology transfers. The different types of solid dispersions based on the molecular arrangement have been highlighted. Some of the practical aspects to be considered for the preparation of solid dispersions, such as selection of carrier, solvent and methods of physicochemical characterization, along with an insight into the molecular arrangement of drugs in solid dispersions are also discussed. In this review, it is intended to discuss the recent advances related on the area of solid dispersions.

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Enhancement of Solubility and Dissolution Rate of Poorly Water Soluble Drug using Cosolvency and Solid Dispersion Techniques

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2008.1.4.6 ◽

1970 ◽

Vol 1 (4) ◽

pp. 349-356

Author(s):

Meka Lingam ◽

Vobalaboina Venkateswarlu

Keyword(s):

Dissolution Rate ◽

Solid Dispersions ◽

Physicochemical Characterization ◽

Aqueous Solubility ◽

Water Soluble ◽

Scanning Calorimetry ◽

Peg 400 ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

Poorly Water Soluble Drug

The low aqueous solubility of celecoxib (CB) and thus its low bioavailability is a problem. Thus, it is suggested to improve the solubility using cosolvency and solid dispersions techniques. Pure CB has solubility of 6.26±0.23µg/ml in water but increased solubility of CB was observed with increasing concentration of cosolvents like PEG 400, ethanol and propylene glycol. Highest solubility (791.06±15.57mg/ml) was observed with cosolvency technique containing the mixture of composition 10:80:10%v/v of water: PEG 400: ethanol. SDs with different polymers like PVP, PEG were prepared and subjected to physicochemical characterization using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), solubility and dissolution studies. These studies reveals that CB exists mainly in amorphous form in prepared solid dispersions of PVP, PEG4000 and PEG6000 further it can also be confirmed by solubility and dissolution rate studies. Solid dispersions of PV5 and PV9 have shown highest saturation solubility and dissolution rate

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Synthesis, Characterization and Bactericidal Activity of a 4-Ammoniumbuthylstyrene-Based Random Copolymer

Polymers ◽

10.3390/polym13071140 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1140

Author(s):

Silvana Alfei ◽

Gabriella Piatti ◽

Debora Caviglia ◽

Anna Maria Schito

Keyword(s):

Antibacterial Activity ◽

Bactericidal Activity ◽

Antimicrobial Agents ◽

Water Solubility ◽

Physicochemical Characterization ◽

Random Copolymer ◽

Water Soluble ◽

Cationic Polymers ◽

Severe Infections

The growing resistance of bacteria to current chemotherapy is a global concern that urgently requires new and effective antimicrobial agents, aimed at curing untreatable infection, reducing unacceptable healthcare costs and human mortality. Cationic polymers, that mimic antimicrobial cationic peptides, represent promising broad-spectrum agents, being less susceptible to develop resistance than low molecular weight antibiotics. We, thus, designed, and herein report, the synthesis and physicochemical characterization of a water-soluble cationic copolymer (P5), obtained by copolymerizing the laboratory-made monomer 4-ammoniumbuthylstyrene hydrochloride with di-methyl-acrylamide as uncharged diluent. The antibacterial activity of P5 was assessed against several multi-drug-resistant clinical isolates of both Gram-positive and Gram-negative species. Except for strains characterized by modifications of the membrane charge, most of the tested isolates were sensible to the new molecule. P5 showed remarkable antibacterial activity against several isolates of genera Enterococcus, Staphylococcus, Pseudomonas, Klebsiella, and against Escherichia coli, Acinetobacter baumannii and Stenotrophomonas maltophilia, displaying a minimum MIC value of 3.15 µM. In time-killing and turbidimetric studies, P5 displayed a rapid non-lytic bactericidal activity. Due to its water-solubility and wide bactericidal spectrum, P5 could represent a promising novel agent capable of overcoming severe infections sustained by bacteria resistant the presently available antibiotics.

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Silver Nanocolloids Loaded with Betulinic Acid with Enhanced Antitumor Potential: Physicochemical Characterization and In Vitro Evaluation

Nanomaterials ◽

10.3390/nano11010152 ◽

2021 ◽

Vol 11 (1) ◽

pp. 152

Author(s):

Iulia Pinzaru ◽

Cristian Sarau ◽

Dorina Coricovac ◽

Iasmina Marcovici ◽

Crinela Utescu ◽

...

Keyword(s):

Antitumor Activity ◽

Betulinic Acid ◽

Water Solubility ◽

Physicochemical Characterization ◽

A549 Cells ◽

Drug Carriers ◽

Biological Evaluation ◽

Correlation Spectroscopy ◽

Hydrodynamic Diameter

Betulinic acid (BA), a natural compound with various health benefits including selective antitumor activity, has a limited applicability in vivo due to its poor water solubility and bioavailability. Thus, this study focused on obtaining a BA nano-sized formulation with improved solubility and enhanced antitumor activity using silver nanocolloids (SilCo and PEG_SilCo) as drug carriers. The synthesis was performed using a chemical method and the physicochemical characterization was achieved applying UV-Vis absorption, transmission electron microscopy (TEM), Raman and photon correlation spectroscopy (PCS). The biological evaluation was conducted on two in vitro experimental models—hepatocellular carcinoma (HepG2) and lung cancer (A549) cell lines. The physicochemical characterization showed the following results: an average hydrodynamic diameter of 32 nm for SilCo_BA and 71 nm for PEG_SilCo_BA, a spherical shape, and a loading capacity of 54.1% for SilCo_BA and 61.9% for PEG_SilCo_BA, respectively. The in vitro assessment revealed a cell type- and time-dependent cytotoxic effect characterized by a decrease in cell viability as follows: (i) SilCo_BA (66.44%) < PEG_SilCo_BA (72.05%) < BA_DMSO (75.30%) in HepG2 cells, and (ii) SilCo_BA (75.28%) < PEG_SilCo_BA (86.80%) < BA_DMSO (87.99%) in A549 cells. The novel silver nanocolloids loaded with BA induced an augmented anticancer effect as compared to BA alone.

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Novel water soluble phosphate prodrugs of taxol® possessing in vivo antitumor activity

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/s0960-894x(00)80058-x ◽

1993 ◽

Vol 3 (8) ◽

pp. 1761-1766 ◽

Cited By ~ 47

Author(s):

Yasutsugu Ueda ◽

Amarendra B. Mikkilineni ◽

Jay O. Knipe ◽

William C. Rose ◽

Anna Maria Casazza ◽

...

Keyword(s):

Antitumor Activity ◽

Water Soluble ◽

Soluble Phosphate ◽

In Vivo Antitumor Activity

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Novel water-soluble polyurethane nanomicelles for cancer chemotherapy: physicochemical characterization and cellular activities

Journal of Nanobiotechnology ◽

10.1186/1477-3155-10-2 ◽

2012 ◽

Vol 10 (1) ◽

pp. 2 ◽

Cited By ~ 32

Author(s):

Ahmad Khosroushahi ◽

Hossein Naderi-Manesh ◽

Hamid Yeganeh ◽

Jaleh Barar ◽

Yadollah Omidi

Keyword(s):

Cancer Chemotherapy ◽

Physicochemical Characterization ◽

Water Soluble

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Novel Gliclazide Electrosprayed Nano-Solid Dispersions: Physicochemical Characterization and Dissolution Evaluation

Advanced Pharmaceutical Bulletin ◽

10.15171/apb.2019.026 ◽

2019 ◽

Vol 9 (2) ◽

pp. 231-240

Author(s):

Khosro Adibkia ◽

Solmaz Ghajar ◽

Karim Osouli-Bostanabad ◽

Niloufar Balaei ◽

Shahram Emami ◽

...

Keyword(s):

Drug Release ◽

Solid Dispersions ◽

In Vitro Release ◽

Physicochemical Characterization ◽

Amorphous State ◽

Water Soluble ◽

Fickian Diffusion ◽

Release Mechanism ◽

Peg 6000

Purpose: In the current study, electrospraying was directed as a novel alternative approach to improve the physicochemical attributes of gliclazide (GLC), as a poorly water-soluble drug, by creating nanocrystalline/amorphous solid dispersions (ESSs). Methods: ESSs were formulated using Eudragit® RS100 and polyethylene glycol (PEG) 6000 as polymeric carriers at various drug: polymer ratios (i.e. 1:5 and 1:10) with different total solution concentrations of 10, 15, and 20% w/v. Morphological, physicochemical, and in-vitro release characteristics of the developed formulations were assessed. Furthermore, GLC dissolution behaviors from ESSs were fitted to various models in order to realize the drug release mechanism. Results: Field emission scanning electron microscopy analyses revealed that the size and morphology of the ESSs were affected by the drug: polymer ratios and solution concentrations. The polymer ratio augmentation led to increase in the particle size while the solution concentration enhancement yielded in a fiber establishment. Differential scanning calorimetry and powder X-ray diffraction investigations demonstrated that the ESSs were present in an amorphous state. Furthermore, the in vitro drug release studies depicted that the samples prepared employing PEG 6000 as carrier enhanced the dissolution rate and the model that appropriately fitted the release behavior of ESSs was Weibull model, where demonstrating a Fickian diffusion as the leading release mechanism. Fourier-transform infrared spectroscopy results showed a probability of complexation or hydrogen bonding, development between GLC and the polymers in the solid state. Conclusion: Hence the electrospraying system avails the both nanosizing and amorphization advantages, therefore, it can be efficiently applied to formulating of ESSs of BCS Class II drugs.

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

Nanomaterials ◽

10.3390/nano11092196 ◽

2021 ◽

Vol 11 (9) ◽

pp. 2196 ◽

Cited By ~ 1

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.

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Epigallocatechin Gallate-Gold Nanoparticles Exhibit Superior Antitumor Activity Compared to Conventional Gold Nanoparticles: Potential Synergistic Interactions

Nanomaterials ◽

10.3390/nano9030396 ◽

2019 ◽

Vol 9 (3) ◽

pp. 396 ◽

Cited By ~ 10

Author(s):

Suhash Chavva ◽

Sachin Deshmukh ◽

Rajashekhar Kanchanapally ◽

Nikhil Tyagi ◽

Jason Coym ◽

...

Keyword(s):

Gold Nanoparticles ◽

Antitumor Activity ◽

Cancer Cells ◽

Cellular Uptake ◽

Nuclear Translocation ◽

Epigallocatechin Gallate ◽

Drug Carriers ◽

Water Soluble ◽

Tetrazolium Salt ◽

Uptake Studies

Epigallocatechin gallate (EGCG) possesses significant antitumor activity and binds to laminin receptors, overexpressed on cancer cells, with high affinity. Gold nanoparticles (GNPs) serve as excellent drug carriers and protect the conjugated drug from enzymatic metabolization. Citrate-gold nanoparticles (C-GNPs) and EGCG-gold nanoparticles (E-GNPs) were synthesized by reduction methods and characterized with UV-visible spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Cytotoxicity of citrate, EGCG, C-GNPs, and E-GNPs was evaluated by the water-soluble tetrazolium salt (WST-1) assay. Nanoparticle cellular uptake studies were performed by TEM and atomic absorption spectroscopy (AAS). Dialysis method was employed to assess drug release. Cell viability studies showed greater growth inhibition by E-GNPs compared to EGCG or C-GNPs. Cellular uptake studies revealed that, unlike C-GNPs, E-GNPs were taken up more efficiently by cancerous cells than noncancerous cells. We found that E-GNP nanoformulation releases EGCG in a sustained fashion. Furthermore, data showed that E-GNPs induced more apoptosis in cancer cells compared to EGCG and C-GNPs. From the mechanistic standpoint, we observed that E-GNPs inhibited the nuclear translocation and transcriptional activity of nuclear factor-kappaB (NF-κB) with greater potency than EGCG, whereas C-GNPs were only minimally effective. Altogether, our data suggest that E-GNPs can serve as potent tumor-selective chemotoxic agents.

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DX-8951f, a Hexacyclic Camptothecin Analog, on a Daily-Times-Five Schedule: A Phase I and Pharmacokinetic Study in Patients With Advanced Solid Malignancies

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.17.3151 ◽

2000 ◽

Vol 18 (17) ◽

pp. 3151-3163 ◽

Cited By ~ 29

Author(s):

Eric K. Rowinsky ◽

Thomas R. Johnson ◽

Charles E. Geyer ◽

Lisa A. Hammond ◽

S. Gail Eckhardt ◽

...

Keyword(s):

Antitumor Activity ◽

Dose Level ◽

Compartment Model ◽

Maximum Tolerated Dose ◽

Preliminary Evidence ◽

Water Soluble ◽

Severe Thrombocytopenia ◽

Phase Ii Studies ◽

Solid Malignancies ◽

Wide Range

PURPOSE: To assess the feasibility of administering DX-8951f (exatecan mesylate), a water-soluble, camptothecin analog, as a 30-minute intravenous infusion daily for 5 days every 3 weeks, determine the maximum-tolerated dose (MTD) and pharmacokinetic (PK) behavior of DX-8951f, and seek preliminary evidence of anticancer activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of DX-8951f. After three patients were treated at the first dose level, doses were to be escalated in increments of 100%, using a single patient at each dose level unless moderate toxicity was observed. The MTD, defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%, was calculated separately for minimally pretreated (MP) and heavily pretreated (HP) patients. The PK and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized. RESULTS: Thirty-six patients were treated with 130 courses of DX-8951f at six dose levels ranging from 0.1 to 0.6 mg/m2/d. Brief, noncumulative neutropenia was the most common toxicity observed. Severe myelosuppression (neutropenia that was protracted and/or associated with fever and/or severe thrombocytopenia) was consistently experienced by HP and MP patients at doses exceeding 0.3 and 0.5 mg/m2/d, respectively. Nonhematologic toxicities (nausea, vomiting, and diarrhea) were also observed, but these effects were rarely severe. Objective antitumor activity included partial responses in one patient each with platinum-resistant extrapulmonary small-cell and fluoropyrimidine- and irinotecan-resistant colorectal carcinoma, and minor responses in patients with prostate, hepatocellular, thymic, primary peritoneal, and irinotecan-resistant colorectal carcinomas. The PKs of total DX-8951 were linear and well fit by a three-compartment model. CONCLUSION: The recommended doses for phase II studies of DX-8951f as a 30-minute infusion daily for 5 days every 3 weeks are 0.5 and 0.3 mg/m2/d for MP and HP patients, respectively. The characteristics of the myelosuppressive effects of DX-8951f, paucity of severe nonhematologic toxicities, and antitumor activity against a wide range of malignancies warrant broad disease-directed evaluations of DX-8951f on this schedule.

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