Polymeric micelles based on photocleavable linkers tethered with a model drug

AbstractPresent research is a preliminary report on the amphiphilic diblock copolymer (mPLA-b-PGMA) comprising hydrophobic methoxy poly(L-lactide) (mPLA) and hydrophilic poly(glycidyl methacrylate) (PGMA) segments was used as a promising drug carrier. Diblock copolymer was synthesized via ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) methods. Methanol first initiated ROP of L-lactide in the presence of tin(II)bis(2-ethylhexanoate) (Sn(oct)2) as a catalyst. The resulting monohydroxyl-terminated polylactic acid (mPLA) was subsequently converted to a bromine-ended macroinitiator (mPLA-Br) by esterification with 2-bromisobutyryl bromide. The copolymer mPLA-b-PGMA was synthesized in a subsequent ATRP of GMA. The obtained polymers were characterized by means of 1H NMR, FTIR, DSC and TGA. The copolymer mPLA-b- PGMA self-assembled into nanoscale micelles in aqueous solutions, as investigated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The TEM image of polymeric micelles showed that the micelles were spherical in shape and that their diameters were in the range of 80-140 nm. Then by using the naproxen as a hydrophobic model drug, the drug-loaded micelles with 81.18 % loading efficiency and 16.24 % loading capacity were prepared. Moreover, in vitro release study of naproxen was performed using dialysis bag in phosphate-buffered solution at 37°C and pH at 7.4. Accordingly, these polymeric micelles may provide as an effective drug carrier for controlled drug release.

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

BioMed Research International ◽

10.1155/2014/579212 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 2

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.

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Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Journal of Nanomaterials ◽

10.1155/2018/8467169 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Dun Fan ◽

Jingmou Yu ◽

Ruiqiao Yan ◽

Xiao Xu ◽

Yunfei Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepg2 Cells ◽

Polymeric Micelles ◽

Phosphate Buffer Solution ◽

Glycyrrhetinic Acid ◽

Buffer Solution ◽

Human Liver Cancer ◽

Model Drug ◽

Preparation And Evaluation

Hepatocellular carcinoma (HCC) is one of the most prevalent fatal diseases and the incidence of HCC is increasing worldwide. Polymeric micelles with targeting groups have drawn great attention as carriers for drug delivery in HCC therapy. Herein, novel glycyrrhetinic acid modified gelatin (GA-GEL) conjugates with three substitution degrees were synthesized and characterized. Doxorubicin (DOX) was applied as a model drug. DOX-loaded GA-GEL (DOX/GA-GEL) micelles were prepared by an emulsion-solvent evaporation method. The mean diameters of DOX/GA-GEL micelles were in the range of 195–235 nm. The encapsulation efficiency of DOX/GA-GEL micelles was 63.6%–96.2%, and the loading content was 8.3%–12.5%. Drug release from DOX-loaded micelles exhibited a biphasic manner in phosphate buffer solution (PBS) at pH 7.4. DOX/GA-GEL could be efficiently accumulated into human liver cancer HepG2 cells. The IC50 values of DOX/GA-GEL-2 and DOX·HCl in HepG2 cells were 0.33 and 0.66 μg/mL, respectively. In vivo imaging analysis demonstrated that the fluorescence signals of DiR-labeled GA-GEL-2 micelles were mainly distributed in liver and H22 orthotopic tumor, indicating that GA-GEL had the liver-targeting activity. Compared to DOX·HCl, DOX/GA-GEL-2 exhibited better antitumor activity in H22 orthotopic mice. Therefore, these results indicated that GA-GEL could be used as carrier of hydrophobic drug for targeting HCC.

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Reduction-responsive dithiomaleimide-based polymeric micelles for controlled anti-cancer drug delivery and bioimaging

Polymer Chemistry ◽

10.1039/c7py01675a ◽

2017 ◽

Vol 8 (46) ◽

pp. 7160-7168 ◽

Cited By ~ 8

Author(s):

Ting Bai ◽

Junjie Du ◽

Jianxin Chen ◽

Xiao Duan ◽

Qiang Zhuang ◽

...

Keyword(s):

Drug Delivery ◽

Block Copolymers ◽

Tumor Cells ◽

Disulfide Bonds ◽

Polymeric Micelles ◽

Amphiphilic Block Copolymers ◽

Cancer Drug ◽

Anti Cancer ◽

Model Drug ◽

Cancer Drug Delivery

The biocompatible amphiphilic block copolymers and the CPT model drug were self-assembled into micelles with bright fluorescence and taken up by tumor cells. Then, the disulfide bonds in the micelles were cleaved to release CPT at a high GSH concentration.

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Microphase separation in binary polymeric micelles

Journal de Physique ◽

10.1051/jphys:01988004901013100 ◽

1988 ◽

Vol 49 (1) ◽

pp. 131-137 ◽

Cited By ~ 16

Author(s):

A. Halperin

Keyword(s):

Polymeric Micelles ◽

Microphase Separation

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Preparation of scutellarin loaded TPGS polymeric micelles and evaluation of its pharmacokinetics and pharmacodynamics effects in rats

Acta Poloniae Pharmaceutica - Drug Research ◽

10.32383/appdr/92248 ◽

2018 ◽

Vol 75 (6) ◽

pp. 1305-1312

Author(s):

Liu Zou ◽

Shujuan Xiong ◽

Xiangping Deng ◽

Juan Liu ◽

Runde Xiong ◽

...

Keyword(s):

Polymeric Micelles ◽

Pharmacokinetics And Pharmacodynamics

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Controlled Release of Metformin Hydrochloride I. In vitro Release from Physical Mixture Containing Xanthan Gum as Hydrophilic Rate Retarding Polymer

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v4i1.200 ◽

1970 ◽

Vol 4 (1) ◽

Author(s):

Mashkura Ashrafi ◽

Jakir Ahmed Chowdhury ◽

Md Selim Reza

Keyword(s):

Controlled Release ◽

Xanthan Gum ◽

In Vitro Release ◽

Correlation Coefficients ◽

High Ratio ◽

Water Soluble ◽

Metformin Hydrochloride ◽

Model Drug ◽

Very High

Capsules of different formulations were prepared by using a hydrophilic polymer, xanthan gum and a filler Ludipress. Metformin hydrochloride, which is an anti-diabetic agent, was used as a model drug here with the aim to formulate sustained release capsules. In the first 6 formulations, metformin hydrochloride and xanthan gum were used in different ratio. Later, Ludipress was added to the formulations in a percentage of 8% to 41%. The total procedure was carried out by physical mixing of the ingredients and filling in capsule shells of size 1. As metformin hydrochloride is a highly water soluble drug, the dissolution test was done in 250 ml distilled water in a thermal shaker (Memmert) with a shaking speed of 50 rpm at 370C &plusmn 0.50C for 6 hours. After the dissolution, the data were treated with different kinetic models. The results found from the graphs and data show that the formulations follow the Higuchian release pattern as they showed correlation coefficients greater than 0.99 and the sustaining effect of the formulations was very high when the xanthan gum was used in a very high ratio with the drug. It was also investigated that the Ludipress extended the sustaining effect of the formulation to some extent. But after a certain period, Ludipress did not show any significant effect as the pores made by the xanthan gum network were already blocked. It is found here that when the metformin hydrochloride and the xanthan gum ratio was 1:1, showed a high percentage of drug release, i.e. 91.80% of drug was released after 6 hours. But With a xanthan gum and metformin hydrochloride ratio of 6:1, a very slow release of the drug was obtained. Only 66.68% of the drug was released after 6 hours. The percent loading in this case was 14%. Again, when Ludipress was used in high ratio, it was found to retard the release rate more prominently. Key words: Metformin Hydrochloride, Xanthan Gum, Controlled release capsule Dhaka Univ. J. Pharm. Sci. Vol.4(1) 2005 The full text is of this article is available at the Dhaka Univ. J. Pharm. Sci. website

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Formulation and Evaluation of Microbially- triggered tablets of Valdecoxib

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v2i1.8841 ◽

2010 ◽

Vol 2 (1) ◽

Author(s):

Surender Verma ◽

S. Singh ◽

D. Mishra ◽

Atul Gupta ◽

Rakesh Sharma

Keyword(s):

Phosphate Buffer ◽

Guar Gum ◽

Oral Route ◽

Matrix Tablets ◽

In Vitro Dissolution ◽

Wet Granulation ◽

Dissolution Study ◽

Caecal Content ◽

Model Drug

The objective of present study was to develop colon targeted drug delivery using bacterially triggered approach through oral route. Valdecoxib (COX-2 inhibitor) was chosen as a model drug in order to target it to colon which may prove useful in inflammatory bowel disease and related disorders. Matrix tablets of Valdecoxib were prepared by wet granulation technique utilizing different ratio of Guar gum and Sodium starch glycholate. The prepared matrix tablets were evaluated for uniformity of weight, uniformity of content, hardness and in vitro dissolution study in simulated gastric and intestinal fluid (Phosphate Buffer pH-1.2, pH-6.8 and pH-7.4), followed by Dissolution study in bio-relevant dissolution media Phosphate Buffer (pH-6.8) containing rat caecal content. The results revealed that the formulated batch had released lesser quantity of drug at pH 1.2 and pH 7.4 in 2 hors whereas in biorelevent dissolution media containing rat caecal content it released significantly higher amount of drug which was also significantly higher than the dissolution media of same pH without caecal content (microflora) and it was concluded that guar gum can be used as a potential carrier for targeting drugs to colon.

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The Effect of Different Superdisintegrants and their Concentrations on the Dissolution of Topiramate Immediate Release Tablets

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.2.6 ◽

2009 ◽

Vol 2 (2) ◽

pp. 531-5366

Author(s):

V A. Vamshi Priya ◽

G. Chandra Sekhara Rao ◽

D. Srinivas Reddy ◽

V. Prabhakar Reddy

Keyword(s):

Immediate Release ◽

Drug Dissolution ◽

Dissolution Profile ◽

Dissolution Medium ◽

Lactose Monohydrate ◽

Sodium Starch Glycolate ◽

Tablet Disintegration ◽

Croscarmellose Sodium ◽

Model Drug ◽

Usp Apparatus

The purpose of this study was to investigate the efficiency of superdisintegrants: sodium starch glycolate, croscarmellose sodium and crospovidone in promoting tablet disintegration and drug dissolution of Topiramate immediate release tablets. The efficiency of superdisintegrants was tested, by considering four concentrations, viz., like 2%, 3%, 4% and 5% in the formulations. The dissolution was carried out in USP apparatus II at 50 rpm with distilled water as a dissolution medium. The dissolution rate of the model drug topiramate was found highly dependent on the tablet disintegration, on the particle size of the superdisintegrant, on the solubility of the drug and also on the type of superdisintegrant in the dissolution medium. There was no effect of the diluent (Lactose monohydrate) on the disintegration of different concentrations of superdisintegrants. These results suggest that, as determined by the f2 metric (similarity factor), the dissolution profile of the formulation containing 4% sodium starch glycolate and lactose monohydrate as a diluent was similar to that of a marketed product.

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