Synthesis of pH-Sensitive and Self-Fluorescent Polymeric Micelles Derived From Rosin and Vegetable Oils via ATRP

Preparation and application of sustainable polymers derived from renewable resources are of great significance. The aim of this study is to synthesize a kind of sustainable polymeric micelles from rosin and vegetable oils via atom transfer radical polymerization (ATRP) and to investigate the doxorubicin delivery properties of these micelles. Dehydroabietic acid–based poly lauryl methacrylate (DA-PLMA) with narrow PDI of 1.13 was prepared in a well-controlled process using rosin as an ATRP initiator. Thereafter, carboxylic groups were introduced to form poly methacrylic acid (PMAA) moieties in DA-PLMA polymer via acid hydrolysis. The resulted DA-PLMA-PMAA could self-assemble in water to form pH-dependent polymeric micelles with a diameter of ∼65 nm and PDI as low as 0.105. Owing to the existence of rosin, DA-PLMA-PMAA micelles also showed self-fluorescence properties. In addition, Dox-loaded micelles were prepared in aqueous solution with the drug-loading capacity as high as 16.0% and showed sustained-release characteristics. These results demonstrate great promise for designing polymeric micellar from rosin and vegetable oils.

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

10.26434/chemrxiv-2021-p3jf5 ◽

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.

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

Journal of Nanomaterials ◽

10.1155/2012/265657 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 6

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.

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High-drug-loading capacity of redox-activated biodegradable nanoplatform for active targeted delivery of chemotherapeutic drugs

Regenerative Biomaterials ◽

10.1093/rb/rbaa027 ◽

2020 ◽

Vol 7 (4) ◽

pp. 359-369

Author(s):

Hai Zhang ◽

Jianqin Yan ◽

Heng Mei ◽

Shengsheng Cai ◽

Sai Li ◽

...

Keyword(s):

Drug Release ◽

Polymeric Micelles ◽

Drug Loading ◽

Active Targeting ◽

Control Group ◽

Loading Capacity ◽

Disulfide Linkage ◽

High Drug ◽

High Drug Loading

Abstract Challenges associated with low-drug-loading capacity, lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy. Herein, we constructed active-targeting, redox-activated polymeric micelles (HPGssML) self-assembled aptamer-decorated, amphiphilic biodegradable poly (benzyl malolactonate-co-ε-caprolactone) copolymer with disulfide linkage and π-conjugated moieties. HPGssML with a homogenous spherical shape and nanosized diameter (∼150 nm) formed a low critical micellar concentration (10−3 mg/mL), suggesting good stability of polymeric micelles. The anticancer drug, doxorubicin (DOX), can be efficiently loaded into the core of micelles with high-drug-loading content via strong π–π interaction, which was verified by a decrease in fluorescence intensity and redshift in UV adsorption of DOX in micelles. The redox sensitivity of polymeric micelles was confirmed by size change and in vitro drug release in a reducing environment. Confocal microscopy and flow cytometry assay demonstrated that conjugating aptamers could enhance specific uptake of HPGssML by cancer cells. An in vitro cytotoxicity study showed that the half-maximal inhibitory concentration (IC50) of DOX-loaded HPGssML was two times lower than that of the control group, demonstrating improved antitumor efficacy. Therefore, the multifunctional biodegradable polymeric micelles can be exploited as a desirable drug carrier for effective cancer treatment.

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Design of dual-responsive nanocarries with high drug loading capacity based on hollow mesoporous organosilica nanoparticles

Materials Chemistry and Physics ◽

10.1016/j.matchemphys.2019.05.025 ◽

2019 ◽

Vol 233 ◽

pp. 230-235 ◽

Cited By ~ 4

Author(s):

Li-li Lu ◽

Wen-ya Xiong ◽

Jun-bin Ma ◽

Tian-fang Gao ◽

Si-yuan Peng ◽

...

Keyword(s):

Drug Loading ◽

Loading Capacity ◽

High Drug ◽

Dual Responsive ◽

Mesoporous Organosilica ◽

High Drug Loading

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

Polymers ◽

10.3390/polym13081254 ◽

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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Present trends in the encapsulation of anticancer drugs

Physical Sciences Reviews ◽

10.1515/psr-2020-0080 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Xavier Montané ◽

Karolina Matulewicz ◽

Karolina Balik ◽

Paulina Modrakowska ◽

Marcin Łuczak ◽

...

Keyword(s):

Carbon Nanotubes ◽

Drug Toxicity ◽

Recent Progress ◽

Polymeric Micelles ◽

Drug Loading ◽

The Body ◽

Inorganic Nanoparticles ◽

Hybrid Nanoparticles ◽

Traditional Medicines ◽

Low Solubility

Abstract Different nanomedicine devices that were developed during the recent years can be suitable candidates for their application in the treatment of various deadly diseases such as cancer. From all the explored devices, the nanoencapsulation of several anticancer medicines is a very promising approach to overcome some drawbacks of traditional medicines: administered dose of the drugs, drug toxicity, low solubility of drugs, uncontrolled drug delivery, resistance offered by the physiological barriers in the body to drugs, among others. In this chapter, the most important and recent progress in the encapsulation of anticancer medicines is examined: methods of preparation of distinct nanoparticles (inorganic nanoparticles, dendrimers, biopolymeric nanoparticles, polymeric micelles, liposomes, polymersomes, carbon nanotubes, quantum dots, and hybrid nanoparticles), drug loading and drug release mechanisms. Furthermore, the possible applications in cancer prevention, diagnosis, and cancer therapy of some of these nanoparticles have been highlighted.

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Exploring the drug loading mechanism of photoresponsive inorganic nanocarriers through molecular dynamics simulations

Nanoscale ◽

10.1039/d1nr01972d ◽

2021 ◽

Author(s):

Stefano Motta ◽

Paulo Siani ◽

Andrea Levy ◽

Cristiana Di Valentin

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Combine Therapy ◽

Drug Loading ◽

Drug Carriers ◽

Inorganic Nanoparticles ◽

Loading Capacity ◽

Physical Stimuli ◽

Dynamics Simulations

Inorganic nanoparticles are gaining increasing attention as drug carriers because they respond to external physical stimuli, allowing to combine therapy with diagnosis. Their drawback is a low drug loading capacity,...

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