Poly(lactide-co-glycolide)-Methoxy-Poly(ethylene glycol) Nanoparticles: Drug Loading and Release Properties

2006 ◽  
Vol 6 (9) ◽  
pp. 3080-3086 ◽  
Author(s):  
Georgia Katsikogianni ◽  
Konstantinos Avgoustakis
Keyword(s):  
Drug Loading ◽  
Double Emulsion ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Molar Ratio ◽  
Nanoparticle Preparation ◽  
Physical Entrapment ◽  
Poly Ethylene ◽  
Phosphate Buffered Saline

In this work, the drug loading and in vitro release properties of PLGA-mPEG nanoparticles were studied. Three methyl-xanthine derivatives differing significantly in aqueous solubility, i.e., caffeine, theophylline, and theobromine, were employed as model drugs. Two different PLGA-mPEG copolymer compositions, namely PLGA(40)mPEG(5) and PLGA(136)mPEG(5), were included in the study. The nanoparticles were prepared by a double emulsion technique. The drug release properties of the nanoparticles in phosphate buffered saline (PBS) and in human plasma were determined. An increase of the drug proportion in the feed led to increased drug loading. The composition of the PLGA-mPEG copolymer (PLGA/mPEG molar ratio) did not appear to affect drug loading and encapsulation. Caffeine exhibited higher loading in the nanoparticles than theobromine and this exhibited a little higher loading than theophylline. Solid-state solubility of the drug in PLGA-mPEG did not affect drug loading. Drug loading and encapsulation in the PLGA-mPEG nanoparticles appeared to be governed by the partition coefficient of the drug between the organic phase and the external aqueous phase employed in nanoparticle preparation. Relatively low loading and encapsulation values were obtained, suggesting that the physical entrapment of drugs in PLGA-mPEG nanoparticles could only be an option in the development of formulations of potent drugs. Only the release of the least water-soluble theobromine was efficiently sustained by its entrapment in the nanoparticles, indicating that the physical entrapment of drugs provides the means for the development of controlled-release PLGA-mPEG nanoparticulate formulations only in the case of drugs with low aqueous solubility.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

scholarly journals Solubility enhancement of carvedilol using drug–drug cocrystallization with hydrochlorothiazide

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Shivarani Eesam ◽  
Jaswanth S. Bhandaru ◽  
Chandana Naliganti ◽  
Ravi Kumar Bobbala ◽  
Raghuram Rao Akkinepally
Keyword(s):  
Aqueous Solubility ◽  
Sem Analysis ◽  
Water Soluble ◽  
High Permeability ◽  
Poorly Water Soluble Drugs ◽  
Drug Discovery And Development ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Dissolution In Vitro

Abstract Background Increasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development. Cocrystallization is one of the techniques to enhance the hydrophilicity of such drugs. Carvedilol (CAR), a nonselective beta/alpha1 blocker, used in the treatment of mild to moderate congestive heart failure and hypertension, is classified under BCS class II with poor aqueous solubility and high permeability. Present work is an attempt to improve the solubility of CAR by preparing cocrystals using hydrochlorothiazide (HCT), a diuretic drug, as coformer. CAR-HCT (2:0.5) cocrystals were prepared by slurry conversion method and were characterized by DSC, PXRD, FTIR, Raman, and SEM analysis. The solubility, stability, and dissolution (in vitro) studies were conducted for the cocrystals. Results The formation of CAR-HCT cocrystals was confirmed based on melting point, DSC thermograms, PXRD data, FTIR and Raman spectra, and finally by SEM micrographs. The solubility of the prepared cocrystals was significantly enhanced (7.3 times), and the dissolution (in vitro) was improved by 2.7 times as compared to pure drug CAR. Further, these cocrystals were also found to be stable for 3 months (90 days). Conclusion It may be inferred that the drug–drug (CAR-HCT) cocrystallization enhances the solubility and dissolution rate of carvedilol significantly. Further, by combining HCT as coformer could well be beneficial pharmacologically too.

scholarly journals Synthesis, Characterization, and Evaluation of Radical Scavenging Ability of Ellagic Acid-Loaded Nanogels

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Gautam Behl ◽  
Monal Sharma ◽  
Saurabh Dahiya ◽  
Aruna Chhikara ◽  
Madhu Chopra
Keyword(s):  
Ellagic Acid ◽  
Encapsulation Efficiency ◽  
Drug Loading ◽  
Radical Scavenging ◽  
Aqueous Solubility ◽  
Loading Level ◽  
Human Cervical Cancer Cell ◽  
Poly Ethylene ◽  
Radical Scavenging Ability ◽  
Acid Loading

Ellagic acid (EA), a potential antioxidant phytochemical has low aqueous solubility and bioavailability. In this paper, encapsulation of ellagic acid has been carried out into the biodegradable disulfide crosslinked poly (ethylene glycol) PEO-based nanogels synthesized via AGET (activator generated electron transfer) ATRP (atom transfer radical polymerization), and their radical scavenging ability was evaluated. The encapsulation of the EA was carried out at two drug loading percentages, that is, 10 and 20 wt.% of the nanogels. 1,1-Diphenyl-2-picryldrazyl (DPPH) assay was utilized in order to assess the radical scavenging ability of the ellagic acid-loaded nanogels. A drug-loading level of about 2.5 wt.% was achieved with encapsulation efficiency of about 25% at 10 wt.% of the EA w.r.t nanogels, which was found to increase to about 4.7 wt.% with decreased encapsulation efficiency of 23.5% as EA content was increased to 20wt.% of the nanogels. Ellagic acid loading was found to be accompanied with increase in the size of the nanogels from144.6±39.52 nm for neat nanogels to217.8±105.5and633±160.1 nm at 2.5 and 4.7 wt.% drug loading level. The nanogels were found to be capable of scavenging radicals and biocompatible on human cervical cancer cell lines (HeLa cells) at appropriate concentrations.

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 Formulation of Nanomicelles to Improve the Solubility and the Oral Absorption of Silymarin

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1688 ◽  
Author(s):  
Vieri Piazzini ◽  
Mario D’Ambrosio ◽  
Cristina Luceri ◽  
Lorenzo Cinci ◽  
Elisa Landucci ◽  
...  
Keyword(s):  
Encapsulation Efficiency ◽  
Oral Absorption ◽  
Drug Loading ◽  
Antioxidant Properties ◽  
Aqueous Solubility ◽  
Average Diameter ◽  
Critical Micellar Concentration ◽  
Polydispersity Index ◽  
Vitamin E Tpgs

Two novel nanomicellar formulations were developed to improve the poor aqueous solubility and the oral absorption of silymarin. Polymeric nanomicelles made of Soluplus and mixed nanomicelles combining Soluplus with d-α-tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS) were prepared using the thin film method. Physicochemical parameters were investigated, in particular the average diameter, the homogeneity (expressed as polydispersity index), the zeta potential, the morphology, the encapsulation efficiency, the drug loading, the critical micellar concentration and the cloud point. The sizes of ~60 nm, the narrow size distribution (polydispersity index ≤0.1) and the encapsulation efficiency >92% indicated the high affinity between silymarin and the core of the nanomicelles. Solubility studies demonstrated that the solubility of silymarin increased by ~6-fold when loaded into nanomicelles. Furthermore, the physical and chemical parameters of SLM-loaded formulations stored at room temperature and in refrigerated conditions (4 °C) were monitored over three months. In vitro stability and release studies in media miming the physiological conditions were also performed. In addition, both formulations did not alter the antioxidant properties of silymarin as evidenced by the 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) assay. The potential of the nanomicelles to increase the intestinal absorption of silymarin was firstly investigated by the parallel artificial membrane permeability assay. Subsequently, transport studies employing Caco-2 cell line demonstrated that mixed nanomicelles statistically enhanced the permeability of silymarin compared to polymeric nanomicelles and unformulated extract. Finally, the uptake studies indicated that both nanomicellar formulations entered into Caco-2 cells via energy-dependent mechanisms.

scholarly journals Enhancing the Oral Bioavailability of Candesartan Cilexetil Loaded Nanostructured Lipid Carriers: In Vitro Characterization and Absorption in Rats after Oral Administration

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1047
Author(s):  
Walid Anwar ◽  
Hamdy Dawaba ◽  
Mohsen Afouna ◽  
Ahmed Samy ◽  
Mohammed Rashed ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Candesartan Cilexetil ◽  
Aqueous Solubility ◽  
Systemic Circulation ◽  
Nanostructured Lipid Carriers ◽  
Water Soluble ◽  
Nanostructured Lipid Carrier ◽  
In Vitro Characterization ◽  
Water Soluble Drugs

Candesartan Cilexetil (CC) is a prodrug widely used in the treatment of hypertension and heart failure, but it has some limitations, such as very poor aqueous solubility, high affinity to P-glycoprotein efflux mechanism, and hepatic first-pass metabolism. Therefore, it has very low oral bioavailability. In this study, glyceryl monostearate (GMS) and Capryol™ 90 were selected as solid and liquid lipids, respectively, to develop CC-NLC (nanostructured lipid carrier). CC was successfully encapsulated into NLP (CC-NLC) to enhance its oral bioavailability. CC-NLC was formulated using a hot homogenization-ultrasonication technique, and the physicochemical properties were characterized. The developed CC-NLC formulation was showed in nanometric size (121.6 ± 6.2 nm) with high encapsulation efficiency (96.23 ± 3.14%). Furthermore, it appeared almost spherical in morphology under a transmission electron microscope. The surgical experiment of the designed CC-NLC for absorption from the gastrointestinal tract revealed that CC-NLC absorption in the stomach was only 15.26% of that in the intestine. Otherwise, cellular uptake study exhibit that CC-NLCs should be internalized through the enterocytes after that transported through the systemic circulation. The pharmacokinetic results indicated that the oral bioavailability of CC was remarkably improved above 2-fold after encapsulation into nanostructured lipid carriers. These results ensured that nanostructured lipid carriers have a highly beneficial effect on improving the oral bioavailability of poorly water-soluble drugs, such as CC.

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 Efflux Inhibitor Bicalutamide Increases Oral Bioavailability of the Poorly Soluble Efflux Substrate Docetaxel in Co-Amorphous Anti-Cancer Combination Therapy

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 266 ◽  
Author(s):  
Adam Bohr ◽  
Thais Nascimento ◽  
Necati Harmankaya ◽  
Johan Weisser ◽  
Yingya Wang ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Water Soluble ◽  
Oral Dosage ◽  
In Vitro Dissolution ◽  
Molar Ratio ◽  
Cancer Drugs ◽  
Efflux Pump Inhibitor ◽  
Anti Cancer ◽  
Amorphous Formulation

Many anti-cancer drugs are difficult to formulate into an oral dosage form because they are both poorly water-soluble and show poor permeability, the latter often as a result of being an intestinal efflux pump substrate. To obtain a more water-soluble formulation, one can take advantage of the higher solubility of the amorphous form of a given drug, whereas to increase permeability, one can make use of an efflux pump inhibitor. In this study, a combination of these two strategies was investigated using the co-amorphous approach, forming an amorphous mixture of two anti-cancer drugs, docetaxel (DTX) and bicalutamide (BIC). The efflux substrate, DTX, was combined with the efflux inhibitor, BIC, and prepared as a single phase co-amorphous mixture at a 1:1 molar ratio using vibrational ball milling. The co-amorphous formulation was tested in vitro and in vivo for its dissolution kinetics, supersaturation properties and pharmacokinetics in rats. The co-amorphous formulation showed a faster in vitro dissolution of both drugs compared to the control groups, but only DTX showed supersaturation (1.9 fold) compared to its equilibrium solubility. The findings for the co-amorphous formulation were in agreement with the pharmacokinetics data, showing a quicker onset in plasma concentration as well as a higher bioavailability for both DTX (15-fold) and BIC (3-fold) compared to the crystalline drugs alone. Furthermore, the co-amorphous formulation remained physically stable over 1.5 years at 4 °C under dry conditions.

scholarly journals Nanoconjugates of a calixresorcinarene derivative with methoxy poly(ethylene glycol) fragments for drug encapsulation

2018 ◽  
Vol 9 ◽  
pp. 2057-2070 ◽  
Author(s):  
Alina M Ermakova ◽  
Julia E Morozova ◽  
Yana V Shalaeva ◽  
Victor V Syakaev ◽  
Aidar T Gubaidullin ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Chloride Solution ◽  
Sodium Chloride Solution ◽  
Organic Substrates ◽  
Poly Ethylene Glycol ◽  
Drug Encapsulation ◽  
Low Toxicity ◽  
Poly Ethylene ◽  
Phosphate Buffered Saline

In order to obtain a non-toxic amphiphilic calixresorcinarene capable to form nanoconjugates for drug encapsulation, tetraundecylcalixresorcinarene functionalized by methoxy poly(ethylene glycol) chains has been synthesized. The macrocycle obtained is characterized by low hemotoxicity. In aqueous solution it forms nanoassociates that are able to encapsulate organic substrates of different hydrophobicity, including drugs (doxorubicin, naproxen, ibuprofen, quercetin). The micelles of the macrocycle slowed down the release of the hydrophilic substrates in vitro. In physiological sodium chloride solution and phosphate-buffered saline, the micelles of the macrocycle acquire thermoresponsive properties and exhibit a temperature-controlled release of doxorubicin in vitro. The combination of the low toxicity and the encapsulation properties of the obtained calixresorcinarene–mPEG conjugate shows promising potential for the use as a supramolecular drug-delivery system.

scholarly journals Size-Dependent Photodynamic Activity of Gold Nanoparticles Conjugate of Water Soluble Purpurin-18-N-Methyl-D-Glucamine

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Byambajav Lkhagvadulam ◽  
Jung Hwa Kim ◽  
Il Yoon ◽  
Young Key Shim
Keyword(s):  
Gold Nanoparticles ◽  
A549 Cells ◽  
Water Soluble ◽  
Molar Ratio ◽  
Anticancer Efficacy ◽  
Molar Ratios ◽  
Size Dependent ◽  
Photodynamic Activity ◽  
Wavelength Absorption

Gold nanoparticles (GNPs) conjugates of water soluble ionic photosensitizer (PS), purpurin-18-N-methyl-D-glucamine (Pu-18-NMGA), were synthesized using various molar ratios between HAuCl4and Pu-18-NMGA without adding any particular reducing agents and surfactants. The PS-GNPs conjugates showed long wavelength absorption of range 702–762 nm, and their different shapes and diameters depend on the molar ratios used in the synthesis.In vitroanticancer efficacy of the PS-GNPs conjugates was investigated by MTT assay against A549 cells, resulting in higher photodynamic activity than that of the free Pu-18-NMGA. Among the PS-GNPs conjugates, the GNPs conjugate from the molar ratio of 1 : 2 (Au(III): Pu-18-NMGA) exhibits the highest photodynamic activity corresponding to bigger size (~60 nm) of the GNPs conjugate which could efficiently transport the PS into the cells than that of smaller size of the GNPs conjugate.

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