Delivery and Anti-Psoriatic Effect of Silibinin-Loaded Polymeric Micelles: An Experimental Study in the Psoriatic Skin Model

2020 ◽  
Vol 17 (9) ◽  
pp. 787-798
Author(s):  
Fateme Chavoshy ◽  
Behzad Sharif Makhmal Zadeh ◽  
Ali Mohammad Tamaddon ◽  
Mohammad Houssin Anbardar
Keyword(s):  
Polymeric Micelles ◽  
Ex Vivo ◽  
Drug Loading ◽  
Polymeric Micelle ◽  
Histological Evaluation ◽  
Psoriatic Skin ◽  
Mice Model ◽  
Area Index ◽  
Psoriasis Treatment ◽  
Drug Localization

Objective: Psoriasis is an inflamed skin disorder associated with the activation of phosphorylation signals in keratinocytes, which leads to proliferation. Phosphorylation signal inhibitors, such as silibinin can inhibit cell proliferation. Unlike current psoriasis treatment approaches that are associated with dangerous side effects; natural components can introduce new trends in psoriasis treatment. The major problem in the topical treatment of psoriasis is drug localization through the psoriasis lesions. Methods: In this study, silibinin-loaded polymeric micelles prepared and characterized for drug loading and release and ex vivo permeation through psoriatic and normal mice skin. The optimized batch was used for the treatment of psoriasis lesions in the mice model. Results: The optimized batch demonstrated mean particle size 18.3 ± 2.1 nm, entrapment efficiency 75.8 ± 5.8%, and prolonged silibinin release. % Silibinin permeated through psoriatic skin after 48 treated by polymeric micelle and aqueous control was 80.35, and 92.6, respectively. Polymeric micelles increased silibinin localization in the psoriatic skin in comparison with control. In psoriatic skin after 7- 10 days treatment by silibinin- loaded polymeric micelle, there was no evidence of psoriasis and the histological evaluation showed no sign of psoriasis. Silibinin-loaded polymeric micelles reduced Psoriasis area index by more than 78% after 14 days. Conclusion: It seems that polymeric micelles increased the effectiveness of silibinin by drug localization into the psoriatic plaque. Topical STAT- 3inhibitors can be introduced as a new strategy in psoriasis treatment.

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 Development and Evaluation of a Water Soluble Fluorometholone Eye Drop Formulation Employing Polymeric Micelle

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 208 ◽  
Author(s):  
Gyubin Noh ◽  
Taekwang Keum ◽  
Jo-Eun Seo ◽  
Jaewoong Choi ◽  
Bastola Rakesh ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Polymeric Micelles ◽  
Ex Vivo ◽  
Physicochemical Characterization ◽  
Polymeric Micelle ◽  
Physical Mixture ◽  
Water Soluble ◽  
Commercial Product ◽  
Corneal Tissue ◽  
Corneal Permeation

Low aqueous solubility of drug causes difficulties in preparation and inconvenience of administration. Polymeric micelles of fluorometholone (FML) using solid dispersion technique were prepared to develop an eye drop formulation with enhanced water solubility. Solid dispersions of FML were prepared at various FML:Soluplus® w/w ratios using solvent evaporation method. A physical mixture was also prepared. Physicochemical characterization was performed with various methods. Ex vivo porcine corneal permeation of polymeric micelle, physical mixture, and commercial product were compared. FML solid dispersion (1:15) showed the highest solubility, which was c.a. 169.6- and 15.3-fold higher than that of pure FML and physical mixture. Characterization showed that the crystalline form of FML changed to amorphous state and polymeric micelles were formed in round micelle. Flucon®, a commercial product of FML, showed significantly large particle size and high poly dispersity index. In contrast, FML polymeric micelle showed submicron size with uniform size distribution. Ex vivo porcine corneal permeation study showed that permeation by polymeric micelles was significantly higher than that by the commercial product and physical mixture. In addition, confocal laser scanning microscopic analysis supported the enhanced porcine corneal tissue permeation property of polymeric micelle. In conclusion, polymeric micelle prepared with solid dispersion using Soluplus® can be a potential nanomedicine for ocular delivery of poorly water-soluble FML.

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 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.

Synthesis, characterization, and property of biodegradable PEG-PCL-PLA terpolymers with miktoarm star and triblock architectures as drug carriers

2018 ◽  
Vol 32 (8) ◽  
pp. 1139-1152 ◽  
Author(s):  
Yixin Zhang ◽  
Song Luo ◽  
Yan Liang ◽  
Hai Zhang ◽  
Xinyu Peng ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Anticancer Drug ◽  
Laser Scanning ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Drug Carriers ◽  
Polymeric Micelle ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Miktoarm Star

A series of amphiphilic terpolymers with miktoarm star and triblock architectures of poly(ethylene glycol) (PEG), poly(ε-caprolactone) (PCL) and poly(l-lactide acid) (PLLA) or poly(DL-lactide acid) (PDLLA) terpolymers were synthesized as carriers for drug delivery. The architecture, molecular weight and crystallization behavior of the terpolymers were characterized. Anticancer drug doxorubicin was encapsulated in the micelles to investigate their drug loading properties. The miktoarm star terpolymers exhibited stronger crystallization capability, smaller size and better stability than that of triblock polymeric micelle, owing to the lower CMC values of miktoarm star polymeric micelle. Furthermore, the drug-loaded miktoarm star polymeric micelles showed the cumulative DOX release account of the micelles with PDLLA blocks was 65.3% while the release account of the corresponding micelles containing PLLA blocks was 45.2%. The IC50 values of drug-loaded miktoarm star polymeric micelle were lower than triblock polymeric micelle. Meanwhile, Confocal laser scanning microscopy (CLSM) and Flow Cytometry results demonstrated that the miktoarm star micelles were more favorable for cellular internalization. The miktoarm star micelles with PDLLA blocks were promising carriers for anticancer drug delivery.

scholarly journals Formulation, Development and Evaluation of Lopinavir Loaded Polymeric Micelles

2020 ◽  
pp. 173-187
Keyword(s):  
Polymeric Micelles ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Polymeric Micelle ◽  
Formulation Development ◽  
Pluronic F68 ◽  
High Entrapment Efficiency ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Polymer Ratio

Lopinavir is the anti HIV drug which is used to treat the HIV-1 infection. In this study we used the single lopinavir drug to formulate the polymeric micelle. This study was done with the two main objectives as Objective:first to enhance the solubility and bioavailability of the BCS class IV drug and second to avoid the combination of lopinavir rand ritonavir and use single lopinavir to preparation of polymeric micelle also to avoid the disadvantages related to the oral administration. Method:The different pluronic (F188 &F127) and co-solvent (Tween80) were chosen & the micelles were prepared by using different Drug: polymer ratio with or without cosolvent and drug Lopinavir. Formulations were been characterized by critical micelle concentration(CMC) value, micellesize,DSC, XRD, loading efficiency, % drug loading and stability.Result:Mixed micelle (hydrophobic &hydrophilic) obtained from optimized batch shows the highest entrapment of 29%with the pluronic F68 with the use of co-solvent and the vesicle size of 0.156µm the DSC, FTIR, XRD study was also done for lopinavir and optimized formulation .Conclusion: The pluronic F68 with the co-solvent showed fairly high entrapment efficiency, loading capacity than the mixed Pluronic in combination

Development and Evaluation of Particulate Microcarriers of Adapalene as a Topical Delivery System

2019 ◽  
Vol 9 (3) ◽  
pp. 222-233
Author(s):  
Divya D. Jain ◽  
Namita D. Desai
Keyword(s):  
Patient Compliance ◽  
Targeted Delivery ◽  
Ex Vivo ◽  
Acne Vulgaris ◽  
Drug Loading ◽  
Topical Therapy ◽  
Skin Irritation ◽  
Topical Delivery ◽  
Diffusion Method ◽  
Topical Gel

Background: Adapalene is a promising third generation retinoid used in the topical treatment of acne vulgaris. However, the major drawback associated with conventional topical therapy of Adapalene is the ‘retinoid reaction’ which is dose-dependent and characterized by erythema, scaling and burning sensation at the application sites. Microparticulate drug delivery can play a major role in reducing side effects and providing better patient compliance due to targeted delivery. Methods: Adapalene microparticles were prepared using quasi emulsion solvent diffusion method. The effects of formulation variables including polymer ratios, amounts of emulsifier, drug loading and process variables such as stirring time and speed on the physical characteristics of microparticles were investigated. The developed microparticles were characterized by DSC and SEM. Adapalene microparticles were incorporated into Carbopol 971 NF gel for ease of topical delivery. Results: Adapalene microparticulate topical gel showed sustained drug release over 8 hours in in vitro studies. The amount of drug retained in the rat skin during ex vivo studies was higher in the microparticulate topical gel (227.43 ± 0.83 µg/cm2) as compared to the marketed formulation (81.4 ± 1.11 µg/cm2) after 8 hours indicating localized and sustained drug action that can be useful in treating acne vulgaris. The safety of optimized Adapalene gel determined by skin irritation studies performed on Sprague Dawley rats showed no irritation potential. Conclusion: Microparticles can provide promising carrier systems to deliver Adapalene, improving patient compliance due to enhanced skin deposition, localized and sustained action with reduced associated irritant effects.

scholarly journals Cyclodextrin-Based Hybrid Polymeric Complex to Overcome Dual Drug Resistance Mechanisms for Cancer Therapy

Polymers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1254
Author(s):  
Lingjie Ke ◽  
Zhiguo Li ◽  
Xiaoshan Fan ◽  
Xian Jun Loh ◽  
Hongwei Cheng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Gene Delivery ◽  
Cell Membrane ◽  
Inclusion Complex ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Resistance Mechanisms ◽  
Polymeric Complex ◽  
Cavity Structure ◽  
Dual Drug

Drug resistance always reduces the efficacy of chemotherapy, and the classical mechanisms of drug resistance include drug pump efflux and anti-apoptosis mediators-mediated non-pump resistance. In addition, the amphiphilic polymeric micelles with good biocompatibility and high stability have been proven to deliver the drug molecules inside the cavity into the cell membrane regardless of the efflux of the cell membrane pump. We designed a cyclodextrin (CD)-based polymeric complex to deliver chemotherapeutic doxorubicin (DOX) and Nur77ΔDBD gene for combating pumps and non-pump resistance simultaneously. The natural cavity structure of the polymeric complex, which was comprised with β-cyclodextrin-graft-(poly(ε-caprolactone)-adamantly (β-CD-PCL-AD) and β-cyclodextrin-graft-(poly(ε-caprolactone)-poly(2-(dimethylamino) ethyl methacrylate) (β-CD-PCL-PDMAEMA), can achieve the efficient drug loading and delivery to overcome pump drug resistance. The excellent Nur77ΔDBD gene delivery can reverse Bcl-2 from the tumor protector to killer for inhibiting non-pump resistance. The presence of terminal adamantyl (AD) could insert into the cavity of β-CD-PCL-PDMAEMA via host-guest interaction, and the releasing rate of polymeric inclusion complex was higher than that of the individual β-CD-PCL-PDMAEMA. The polymeric inclusion complex can efficiently deliver the Nur77ΔDBD gene than polyethylenimine (PEI-25k), which is a golden standard for nonviral vector gene delivery. The higher transfection efficacy, rapid DOX cellular uptake, and significant synergetic tumor cell viability inhibition were achieved in a pump and non-pump drug resistance cell model. The combined strategy with dual drug resistance mechanisms holds great potential to combat drug-resistant cancer.

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