scholarly journals Permeability of Ciprofloxacin-Loaded Polymeric Micelles Including Ginsenoside as P-glycoprotein Inhibitor through a Caco-2 Cells Monolayer as an Intestinal Absorption Model

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1904 ◽  
Author(s):  
Behzad Sharif Makhmal Zadeh ◽  
Golbarg Esfahani ◽  
Anayatollah Salimi
Keyword(s):  
Particle Size ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Aqueous Solubility ◽  
Polymeric Micelle ◽  
Maximum Effect ◽  
Drug Permeability ◽  
Intestinal Membrane ◽  
Full Factorial ◽  
Dose Dependent

The low oral bioavailability of ciprofloxacin is associated with two distinct challenges: its low aqueous solubility and efflux by p-glycoproteins (P-gp) in the intestinal membrane. Several studies were conducted in order to improve its solubility and permeability through the gastrointestinal membrane. In this study, in a full factorial design study, eight polymeric micelles were prepared and their characteristics, including particle size, loading and release rate were evaluated. Polymeric micelles demonstrated particle sizes below 190 nm and 27–88% loading efficiency. Drug release was affected by drug solubility, polymeric micelle erosion and swelling in simulated gastrointestinal fluids. An optimized polymeric micelle was prepared based on appropriate characteristics such as high drug loading and low particle size; and was used for a permeation study on Caco-2 cells. Optimized polymeric micelles with and without ginsenoside and ginsenoside alone enhanced drug permeability through Caco-2 cells significantly in the absorptive direction. The effect of ginsenoside was dose dependent and the maximum effect was seen in 0.23 mg/mL concentration. Results showed that P-gp may not be responsible for ciprofloxacin secretion into the gut. The main mechanism of ciprofloxacin transport through Caco-2 cells in both directions is active diffusion and P-gp has inhibitory effects on ciprofloxacin permeability in the absorptive direction that was blocked by ginsenoside and micelles without ginsenoside.

scholarly journals Preparation and characterization of N-benzyl-N,O-succinyl chitosan polymeric micelles for solubilization of poorly soluble non-steroidal anti-inflammatory drugs

2017 ◽  
Vol 16 (10) ◽  
pp. 2349-2357
Author(s):  
Thisirak Woraphatphadung ◽  
Warayuth Sajomsang ◽  
Theerasak Rojanarata ◽  
Prasert Akkaramongkolporn ◽  
Tanasait Ngawhirunpat ◽  
...  
Keyword(s):  
Particle Size ◽  
Surface Charge ◽  
Polymeric Micelles ◽  
Rank Order ◽  
Drug Loading ◽  
Polymer Concentration ◽  
Water Soluble ◽  
Loading Efficiency ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Purpose: To investigate the solubilization of poorly water-soluble non-steroidal  anti-inflammatory drugs (NSAIDs) in N-benzyl-N,O-succinyl chitosan (BSCS)  polymeric micellesMethods: BSCS was synthesized by reductive amination and succinylation,  respectively. NSAIDs; meloxicam (MX), piroxicam (PRX), ketoprofen (KP) and indomethacin (IND) were entrapped in the hydrophobic inner cores by evaporation method. The effects of drug structure on loading efficiency, particle size and surface charge of micelles were investigated.Results: The critical micelle concentration of BSCS micelles was 0.0385 mg/mL and cytotoxicity on Caco-2 cells depends on the polymer concentration (IC50 = 3.23 ± 0.08 mg/mL). BSCS micelles were able to entrap MX, PRX, KP and IND and also improve the solubility of drugs. Drug loading efficiency was highly dependent on the drug molecules. The drug loading capacity of these BSCS micelles was in the following rank order: KP (282.9 μg/mg) > PRX (200.8 μg/mg) > MX (73.7 μg/mg) > IND (41.2 μg/mg). The highest loading efficiency was observed in KP-loaded BSCS micelles due to the attractive force between phenyl groups of KP and benzyl groups of the polymer. Particle size and surface charge were in the range of 312 - 433 nm and -38 to -41 mV, respectively.Conclusion: BSCS copolymer presents desirable attributes for enhancing the  solubility of hydrophobic drugs. Moreover, BSCS polymeric micelles might be beneficial carrier in a drug delivery system.Keywords: BSCS, polymeric micelles, solubilization, non-steroidal anti-inflammatory drugs

scholarly journals Designing Highly Stable Poly(sarcosine)-based Telodendrimer Micelles with High Drug Content Exemplified with Fulvestrant

2021 ◽  
Author(s):  
Qing Yu ◽  
Richard England ◽  
Anders Gunnarsson ◽  
Robert Luxenhofer ◽  
Kevin Treacher ◽  
...  
Keyword(s):  
Colloidal Stability ◽  
Water Solubility ◽  
High Efficiency ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Polymeric Micelle ◽  
Chemotherapeutic Agents ◽  
Loading Capacity ◽  
High Drug ◽  
Linear Poly

Polymeric micelles have been extensively used as nanocarriers for the delivery of chemotherapeutic agents aiming to improve their efficacy in cancer treatment. However, poor loading capacity, premature drug release, non-uniformity and reproducibility still remain the major challenges. To create a stable polymeric micelle with high drug loading, a telodendrimer micelle was developed as a nanocarrier for fulvestrant, as an example of a drug that has extremely poor water solubility (sub nanomolar range). Telodendrimers were prepared by synthesis of a hydrophilic linear poly(sarcosine) and growing a lysine dendron from the chain terminal amine by a divergent synthesis. At the periphery of the dendritic block, 4, 8, and 16 fulvestrant molecules were conjugated to the lysine dendron creating a hydrophobic block. Having drug as part of the carrier not only reduces the usage of the inert carrier materials but also prevent the drugs from leakage and premature release by diffusion. The self-assembled telodendrimer micelles demonstrated good colloidal stability (CMC < 2 µM) in buffer and were uniform in size. In addition, these telodendrimer micelles could solubilize additional fulvestrant yielding an excellent overall drug loading capacity of up to 77 wt.% total drug load (summation of conjugated and encapsulated). Importantly, the size of the micelles could be tuned between 25-150 nm by controlling (i) the ratio between hydrophilic and hydrophobic blocks and (ii) the amount of encapsulated fulvestrant. The versatility of these telodendrimer-based micelle systems to both conjugate and encapsulate drug with high efficiency and stability, in addition to possessing other tuneable properties makes it a promising drug delivery system for a range of active pharmaceutical ingredients and therapeutic targets.

scholarly journals Inulin-Grafted Stearate (In-g-St) as the Effective Self-Assembling Polymeric Micelle: Synthesis and Evaluation for the Delivery of Betamethasone

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Gholamabbas Chehardoli ◽  
Parham Norouzian ◽  
Farzin Firozian
Keyword(s):  
Zeta Potential ◽  
Sustained Release ◽  
Targeted Delivery ◽  
Encapsulation Efficiency ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Polymeric Micelle ◽  
Water Soluble ◽  
Burst Release ◽  
Potential Measurement

Background. Betamethasone as a corticosteroid drug is commonly used for the treatment of rheumatoid arthritis. Unfortunately, betamethasone is a low water-soluble drug and its efficacy is low. So an attractive strategy is the targeted delivery of betamethasone to the damaged joint using polymeric micelle-based carriers. Methods. Inulin-grafted stearate (In-g-St) was synthesized via the reaction of stearoyl chloride and inulin, then characterized by FT-IR and H-NMR. In-g-St forms micelles in the presence of betamethasone. The prepared polymeric micelles were characterized for size, zeta potential, drug loading, particles’ morphology, critical micelle concentration (CMC), and encapsulation efficiency. So sustained release polymeric micelles of betamethasone were developed by employing In-g-St. Results. The measurement of particle size showed a mean diameter of 60 and 130 nm for 10% and 20% drug-loaded micelles, respectively, and SEM showed that the particle’s morphologies are spherical. Zeta potential measurement for the drug-containing micelles showed a value of -11.8 mV. Drug loading efficiency and the encapsulation efficiency were 6.36% and 63.6%, as well as 18.97% and 94.88% for 10% and 20%, respectively. 20% drug-loaded polymer showed a small burst release of betamethasone at the first 3 h which was followed by sustained release in the next 24 h. Furthermore, the formula with 10% exhibited good sustained release properties except for the minor initial burst release. Conclusion. Data from the zeta potential, CMC, drug loading capacity, and in vitro drug release studies indicated that In-g-St polymeric micelles can be suitable candidates for the efficient delivery of hydrophobic drugs like betamethasone.

scholarly journals Effect of Molecular Weight and Molar Ratio of Dextran on Self-Assembly of Dextran Stearate Polymeric Micelles as Nanocarriers for Etoposide

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jaleh Varshosaz ◽  
Farshid Hassanzadeh ◽  
Hojjat Sadeghi ◽  
Farzin Firozian ◽  
Mina Mirian
Keyword(s):  
Molecular Weight ◽  
Particle Size ◽  
Zeta Potential ◽  
Self Assembly ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Molar Ratio ◽  
Loading Capacity ◽  
Hydrophobic Polymers ◽  
Polymer Surfactants

Amphiphilic polymer surfactants are composed of hydrophilic and hydrophobic polymers and are widely used in targeted drug delivery. The purpose of this study was the evaluation of the effect of molecular weight and molar ratio of dextran on physicochemical properties of dextran stearate polymeric micelles. Dextran stearate was synthesized by acylation of dextran with stearoyl chloride. Etoposide loaded polymeric micelles were prepared by dialysis method. The resulting micelles were evaluated for particle size, zeta potential, critical micelle concentration (CMC), drug loading capacity, and release efficiency. Cytotoxicity and cellular uptake of micelles were studied in CT-26 colorectal carcinoma cell line. Molecular weight and molar ratio of dextran-stearate were impressive on zeta potential, CMC, drug loading capacity, and release efficiency. Unlike polymer molecular weight, molar ratio of stearate had a significant effect on cytotoxicity and particle size of etoposide loaded micelles. Although molecular weight of dextran had no significant effect on cytotoxicity of micelles on CT-26 cells, it had drastic attributes for stability of polymeric micelles. Consequently, both variables of molecular weight of dextran and molar ratio of stearate should be taken into account to have a stable and effective micelle of dextran-stearate.

scholarly journals Impact of Core-Forming Segment Structure on Drug Loading in Biodegradable Polymeric Micelles Using PEG-b-Poly(lactide-co-depsipeptide) Block Copolymers

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Akihiro Takahashi ◽  
Yuta Ozaki ◽  
Akinori Kuzuya ◽  
Yuichi Ohya
Keyword(s):  
Block Copolymers ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Polymeric Micelle ◽  
Molecular Weights ◽  
The Core ◽  
Drug Delivery Carrier ◽  
Loading Efficiency ◽  
Drug Loading Efficiency ◽  
Model Drug

We synthesized series of amphiphilic AB-type block copolymers having systematic variation in the core-forming segments using poly(lactide-co-depsipeptide)s as a hydrophobic segment and prepared polymeric micelles using the block copolymers, PEG-b-poly(lactide-co-depsipeptide). We then discussed the relationship between the core-forming segment structure and drug loading efficiency for the polymeric micelles. PEG-b-poly(lactide-co-depsipeptide)s, PEG-b-PLGL containingl-leucine (Leu), and PEG-b-PLGF containingl-phenylalanine (Phe), with similar molecular weights and various mole fractions of depsipeptide units, were synthesized. Polymeric micelles entrapping model drug (fluorescein, FL) were prepared using these copolymers. As a result, PEG-b-poly(lactide-co-depsipeptide) micelles showed higher drug loading compared with PEG-b-PLLA and PEG-b-PDLLA as controls. The drug loading increased with increase in the mole fraction of depsipeptide unit in the hydrophobic segments. The introduction of aliphatic and aromatic depsipeptide units was effective to achieve higher FL loading into the micelles. PEG-b-PLGL micelle showed higher drug loading than PEG-b-PLGF micelle when the amount of FL in feed was high. These results obtained in this study should be useful for strategic design of polymeric micelle-type drug delivery carrier with high drug loading efficiency.

scholarly journals Acid-Responsive Adamantane-Cored Amphiphilic Block Polymers as Platforms for Drug Delivery

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 188
Author(s):  
Weiqiu Wen ◽  
Chong Guo ◽  
Jianwei Guo
Keyword(s):  
Drug Delivery ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Controlled Drug Release ◽  
Polymeric Micelle ◽  
Monomethyl Ether ◽  
Particle Sizes ◽  
Anticancer Efficacy ◽  
Decrease Rate ◽  
Anticancer Drug Delivery

Four-arm star-shaped (denoted as ‘S’) polymer adamantane-[poly(lactic-co-glycolic acid)-b-poly(N,N’-diethylaminoethyl methacrylate) poly(ethylene glycol) monomethyl ether]4 (S-PLGA-D-P) and its linear (denoted as ‘L’) counterpart (L-PLGA-D-P) were synthesized, then their self-assembled micelles were further developed to be platforms for anticancer drug delivery. Two types of polymeric micelles exhibited strong pH-responsiveness and good drug loading capacity (21.6% for S-PLGA-D-P and 22.9% for L-PLGA-D-P). Using doxorubicin (DOX) as the model drug, their DOX-loaded micelles displayed well controlled drug release behavior (18.5–19.0% of DOX release at pH 7.4 and 77.6–78.8% of DOX release at pH 5.0 within 80 h), good cytocompatibility against NIH-3T3 cells and effective anticancer efficacy against MCF-7 cells. However, the star-shaped polymeric micelles exhibited preferable stability, which was confirmed by the lower critical micelle concentration (CMC 0.0034 mg/mL) and decrease rate of particle sizes after 7 days incubation (3.5%), compared with the linear polymeric micelle L-PLGA-D-P (CMC 0.0070 mg/mL, decrease rate of particle sizes was 9.6%). Overall, these developed polymeric micelles have promising application as drug delivery system in cancer therapy.

Dissolution behavior of Olmesartan Medoxomil drug in Polymeric Micelles of Soluplus and Pluronic F127

2021 ◽  
pp. 2200-2204
Author(s):  
Suchetana Dutta ◽  
P. K. Kulkarni ◽  
Shailesh T.
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Olmesartan Medoxomil ◽  
Water Soluble ◽  
Pluronic F127 ◽  
Dissolution Behavior ◽  
Compatibility Study ◽  
Poorly Water Soluble

The aim of the present work was to study the dissolution behaviour of a poorly water-soluble Olmesartan Medoxomil (class II drug), by forming polymeric micelles (PMs) of SoluPlus and Pluronic F127. Polymeric Micelles of SoluPlus and Pluronic F127 were prepared by the co-solvent evaporation method. Drug and excipient compatibility study were carried out by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry. The formulations were evaluated for particle size, Zeta Potential, Solubility studies, drug loading and encapsulation efficiency. Scanning Electron Microscopy (SEM) analysis was performed to study the surface morphology of the PMs. The SEM images showed spherical surface of the micelles. The drug loading efficiency was more for SoluPlus micelles compared to Pluronic F127 micelles. The Polymeric micelles showed negative zeta potential value indicating that they are stable and resist aggregation. The particle size was around 100nm and polydispersity index was less than 1 indicating uniform size distribution. The drug release from the SoluPlus micelles was higher than the Pluronic micelles. These results suggest that the polymeric micelles can be used to increase the solubility of poorly water-soluble drugs.

scholarly journals Uptake of Etoposide in CT-26 Cells of Colorectal Cancer Using Folate Targeted Dextran Stearate Polymeric Micelles

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jaleh Varshosaz ◽  
Farshid Hassanzadeh ◽  
Hojjat Sadeghi-Aliabadi ◽  
Farzin Firozian
Keyword(s):  
Colorectal Cancer ◽  
Particle Size ◽  
Nmr Spectroscopy ◽  
Zeta Potential ◽  
Cellular Uptake ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Research Areas ◽  
Ir And Nmr Spectroscopy ◽  
Ft Ir

Targeted drug delivery using folate receptors is one of the most interesting chemotherapeutic research areas over the past few years. A novel folate targeted copolymer was synthesized using dextran stearate coupled to folic acid. FT-IR and NMR spectroscopy were used to confirm successful conjugation. Micelles prepared using this copolymer were characterized for their particle size, zeta potential, critical micelle concentration (CMC), drug loading capacity, and release efficiency. Cytotoxicity and cellular uptake of the micelles were estimated using CT-26 colorectal carcinoma cell line. FT-IR and NMR spectroscopy confirmed production of folate grafted dextran stearate copolymer. Low CMC value indicates that the copolymers are suitable for preparation of stable micelles useful in parenteral dosage forms. Particle size and zeta potential of the targeted nanoparticles were105.5±2.0 nm and −21.2 mV, respectively. IC50of etoposide loaded in folate grafted dextran stearate enhanced about 20-fold compared to the pure drug (0.49±0.11 μg/mL versus9.41±0.52 μg/mL). It seems that etoposide loaded in micelles of folate grafted dextran stearate copolymer is promising in reducing drug resistance of colorectal cancer by boosting etoposide cellular uptake.

Dissolution Behaviour of the Poorly Water-Soluble Drug Mefenamic Acid from Polymeric Micelles

2018 ◽  
Vol 11 (3) ◽  
pp. 4098-4105
Author(s):  
Tibey Mary Koshy ◽  
Parthasarathi K Kulkarni
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Mefenamic Acid ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Water Soluble ◽  
Pluronic F127 ◽  
Compatibility Study ◽  
Dissolution Behaviour ◽  
Poorly Water Soluble

The aim of the work was to study the dissolution behaviour of the poorlywater-soluble drug mefenamic acid (MA), a NSAID, from polymeric micelles (PMs) of Pluronic F127 and DexbLG micelles.DexbLG Copolymer was synthesised by cross-linking reaction using Dextran and PLGA. Drug excipient compatibility study was carried out by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). Pluronic F 127 and DexbLG Polymeric micelles formulation were prepared by co-solvent evaporation technique. Formulations were evaluated for particle size, Zeta potential, solubility studies, drug loading and encapsulation efficiency. Scanning electron microscopy (SEM) analysis was performed to study the size and surface morphology of the PMs. SEM image showed smooth surfaced spherical micelles. The drug loading efficiency was more inpluronic F 127 micelles. Polymeric micelles showed negative Zeta potential value indicating that they are stable and resist aggregation. Solubility of MA has increased to 6 - 13 folds from PMs of pluronic F127 and 4-11folds from DexbLG micelles. Particle size was less than 100 nm and polydispersity index was less than 0.5 indicating uniform size distribution. Percentage cumulative drug release from the Pluronic micelles was higher than DexbLG micelles. It can be concluded that MA PMs formulation has significantly increased the solubility and thereby increases the dissolution of the drug.These results suggest that polymeric micelles can be used to increase the solubility of poorly water-soluble drugs.  

scholarly journals Folate-Targeted Curcumin-Encapsulated Micellar Nanosystem for Chemotherapy and Curcumin-Mediated Photodynamic Therapy

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2280
Author(s):  
Yun Hsuan Lin ◽  
Ching-Yi Chen
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Cells ◽  
High Efficiency ◽  
Folate Receptor ◽  
Drug Loading ◽  
Aqueous Solubility ◽  
Polymeric Micelle ◽  
In Vitro Cytotoxicity ◽  
Efficient Delivery

Curcumin (CUR) is a natural phenolic product used as a high-efficiency and low-toxicity anticancer drug and photosensitizer. However, it has a poor aqueous solubility and a lack of target specificity, which limits its clinical applications. Hence, we developed a folate-conjugated polymeric micelle to enhance the efficient delivery of CUR for effective cancer cell targeting and anticancer efficiency. A series of biocompatible folate-conjugated poly(2-(methacryloyloxy)ethylphosphoryl- choline)-b-poly(ε-caprolactone) (FPM) was synthesized with different hydrophobic lengths and folate contents. The prepared CUR-loaded micelles (CUR-FPM) possessed several superior properties, including an excellent drug loading capacity (6.3 ± 1.2%), improved CUR aqueous stability, fast-sustained CUR release in an acidic environment, and efficient intracellular production of reactive oxygen species. The in vitro cytotoxicity demonstrated that the CUR-FPM micelles efficiently suppressed the growth of HeLa cells (folate-receptor overexpression) compared to that of HT-29 cells, and a competition study showed less cytotoxic effect when free folic acid blocked the folate receptor, indicating the folate conjugation played the role of targeting the specific cells well. Moreover, the CUR-mediated photodynamic therapy (PDT) by CUR-FPM micelles under irradiation further inhibited the proliferation of cancer cells. All these results indicate that the CUR-FPM micelles could be a promising delivery system for folate-overexpressing cancer cells, complementary chemotherapy, and CUR-mediated photodynamic therapy.

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