Facile synthesis of ABCDE‐type H‐shaped quintopolymers by combination of ATRP,ROP, and click chemistry and their potential applications as drug carriers

A facile approach to synthesis of ABCDE‐type H‐shaped quintopolymer comprising polystyrene (PSt, C) main chain and poly(ethylene glycol) (PEG, A), poly(ε‐caprolactone) (PCL, B), poly(L ‐lactide) (PLLA, D), and poly(acrylic acid) (PAA, E) side chains was described, and physicochemical properties and potential applications as drug carriers of copolymers obtained were investigated. Azide‐alkyne cycloaddition reaction and hydrolysis were used to synthesize well‐defined H‐shaped quintopolymer. Cytotoxicity studies revealed H‐shaped copolymer aggregates were nontoxic and biocompatible, and drug loading and release properties were affected by macromolecular architecture, chemical composition, and pH value. The release rate of doxorubicin from copolymer aggregates at pH 7.4 was decreased in the order PAA‐b‐PLLA > H‐shaped copolymer > PEG‐PCL‐PSt star, and the release kinetics at lower pH was faster. The H‐shaped copolymer aggregates have a potential as controlled delivery vehicles due to their excellent storage stability, satisfactory drug loading capacity, and pH‐sensitive release rate of doxorubicin. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Novel drug‐eluting soy‐protein structures for wound healing applications

Naturally derived materials are becoming widely used in the biomedical field. Soy protein has advantages over the various types of natural proteins employed for biomedical applications due to its low price, nonanimal origin, and relatively long storage time and stability. In the current study, novel drug‐eluting soy‐protein films for wound healing applications were developed and studied. The films were prepared using the solvent casting technique. The analgesic drug bupivacaine and two types of wide range antibiotics (gentamicin and clindamycin) were incorporated into the soy‐protein films. The effect of drug incorporation and plasticizers content on the films' mechanical properties, drug release profiles, and cell viability was studied. Drug incorporation had a softening effect of the films, lowering mechanical strength and increasing ductility. Release profiles of bupivacaine and clindamycin exhibited high burst release of 80% to 90% of encapsulated drug within 6 hours, followed by continuous release in a decreasing rate for a period of 2 to 4 days. Gentamicin release was prolonged, probably due to interaction between the gentamicin and the polymer chains. Hybrid soy‐protein/poly (Dl‐lactic‐co‐glycolic acid) (PDLGA) microspheres structure showed potential for long and sustained release of bupivacaine. Films with no drugs and films loaded with gentamicin were found to be noncytotoxic for human fibroblasts, while bupivacaine and clindamycin were found to have some effect on cell growth. In conclusion, our new drug‐loaded soy‐protein films combine good mechanical properties and biocompatibility, with desired drug release profiles, and can therefore be potentially very useful as burn and ulcer dressings.     

Microencapsulation of protein‐loaded polysaccharide particles within poly(D,L‐lactic‐co‐glycolic acid) microspheres using S/O/W: characterization and release studies

This report demonstrates a process to form polysaccharide glassy particles without water–oil or water–air interfaces as well as ionic polymers and its application in formulating sustained‐release dosage forms for structurally delicate proteins. When a co‐solution containing dextran and polyethylene glycol (PEG) was subjected to freeze‐drying, the dextran separated out of the solution to form dispersed phases surrounded by a PEG‐rich continuous phase and was solidified during subsequent lyophilization to fine glassy particles, 1–2 µm in diameter. Water‐soluble proteins can easily be loaded in these glassy particles due to preferential partition and become resistant to organic solvents simply by adding them into the dextran‐PEG co‐solution. After washing away the PEG continuous phase with organic solvents, the protein‐containing glassy particles can be suspended in a hydrophobic polymer solution and formulated into various pharmaceutical dosage forms and medical devices for sustained‐release protein delivery. In the present study, myoglobin, bovine serum albumin (BSA), and β‐galactosidase (β‐gal) were formulated in PLGA mcirospheres and as model proteins using this glassy particulate approach, and subjected to a series of assays for release kinetics, structural integrity, and bioactivity. The experimental results indicated that this system offered well preserved protein integrity and bioactivity as well as significantly improved protein release kinetics. Copyright © 2008 John Wiley & Sons, Ltd.     

In situ forming PLGA implant for 90 days controlled release of leuprolide acetate for treatment of prostate cancer

In prostate cancer, hormone therapy via leuprolide acetate drug (LUP) is used to lower the level of testosterone down to castration level to effectively control the development of prostate cancer. The objective of this study was to evaluate the effective parameters in degradation and controlled release of an injectable in situ formed polymeric implant, loaded with leuprolide acetate, in order to achieve an optimum formulation for sustained drug release for 90 days with minimum burst release. The main problem associating with such implants is their high burst release. Designing an injectable implant with sustained and minimum burst release has thus become an attractive challenge in drug delivery field. Effects of type of poly(lactic‐co‐glycolic acid) 75:25 copolymers (RG752, RG756) and addition of nano‐hydroxyapatite (HA) particles on degradation rates of the implants and release profiles were examined in vitro and in vivo in a rabbit animal model. Results showed that implants containing polymers with higher molecular weights had significantly lower weight loss and molecular weight reduction. Adding nanoparticles of hydroxyapatite into poly(lactic‐co‐glycolic acid) implants caused further reduction in degradation rates, leading to a more sustained drug release in vivo, with reduced burst release. Different conventional kinetic models were applied to drug release and degradation data. The degradation data fit well to the first‐order degradation model. Higuchi model was the best kinetic release model fitted to the experimental in vitro release data. This study led to an optimum formulation (RG756:RG752 3:1 + 5% HA) with sustained leuprolide release and testosterone suppression over a 90‐day period with significant decrease of burst release phase (50%, p < 0.001) compared with the conventional Eligard formulation. The histopathology test showed that the formulated implant had no effects of toxicity or tissue necrosis in organs of the animal model. Copyright © 2017 John Wiley & Sons, Ltd.     

Facile Fabrication of Thermo‐Responsive and Reduction‐Sensitive Polymeric Micelles for Anticancer Drug Delivery

The development of thermo‐responsive and reduction‐sensitive polymeric micelles based on an amphiphilic block copolymer poly[(PEG‐MEMA)‐co‐(Boc‐Cyst‐MMAm)]‐block‐PEG (denoted PEG‐P‐SS‐HP) for the intracellular delivery of anticancer drugs is reported. PTX, as model drug, was loaded into the PEG‐P‐SS‐HP micelles with an encapsulation efficiency >90%, resulting in a high drug loading content (up to 35 wt%). The PTX‐loaded PEG‐P‐SS‐HP micelles show slow drug release in PBS and rapid release after incubation with DTT. The PTX‐loaded micelles display a better cytotoxic effect than the free drug, whereas empty micelles are found to be non‐toxic. The thermo‐responsive and reduction‐sensitive polymeric micelles described may serve as promising carriers for cytostatic drugs.

     

Synthesis and characterization of poly(ethylene glycol)‐based thermo‐responsive polyurethane hydrogels for controlled drug release

The thermo‐responsiveness, swelling and mechanical properties of a series of novel poly(ester‐ether urethane) hydrogels have been investigated. These thermo‐sensitive hydrogels were obtained by combining hydrophobic biodegradable poly(ε‐caprolactone) diols and hydrophilic two‐, three‐ and four‐arm hydroxyl terminated poly(ethylene glycol) (PEG) of various molecular weights, using hexamethylene diisocyanate, dichloroethane as solvent and a tin‐based catalyst. The use of multifunctional PEGs leads to the formation of covalent crosslinking points allowing an additional control of the swelling capability. Thus, it was found that tuning the hydrophilic/hydrophobic balance and the crosslinking degree by changing the composition, the swelling and the thermo‐responsive behavior of these hydrogels could be modulated. The obtained hydrogels showed a volume transition at around room temperature. Therefore, and taking into account their biocompatibility, these hydrogels show promising properties for biomedical applications, such as drug delivery. Thus, the loading and release of diltiazem hydrochloride, an antihypertensive drug used as model, were investigated. These new PEG polyurethane hydrogels were able to incorporate a high amount of drug providing a sustained release after an initial burst effect. Copyright © 2013 John Wiley & Sons, Ltd.     

Electrostatic Layer‐by‐Layer Assembly of Polycation and DNA Multilayer Films by Real‐time Surface Plasmon Resonance Technique

The assembly of alternating DNA and positively charged poly‐(dimethyldiallylammonium chloride) (PDDA) multilayer films by electrostatic layer‐by‐layer adsorption has been studied. Real time surface plasmon resonance (BIAcore) technique was used to characterize and monitor the formation of multilayer films in solution in real time continuously. The results indicate that the uniform multilayer can be obtained on the poly‐(ethylenimine) (PEI) coated substrate surface. The kinetics of the adsorption of DNA on PDDA surface was also studied by real‐time BIAcore technique, and the observed rate constant was calculated using a Langmuir model (k_obs = (1.28 ± 0.08) × 10^?2s^?1).     

Stimuli‐responsive zein‐based nanoparticles as a potential carrier for ellipticine: Synthesis,release, and in vitro delivery

In the present research, we have investigated a drug delivery system based on the pH‐responsive behaviors of zein colloidal nanoparticles coated with sodium caseinate (SC) and poly ethylene imine (PEI). These systematically designed nanoparticles were used as nanocarriers for encapsulation of ellipticine (EPT), as an anticancer drug. SC and PEI coatings were applied through electrostatic adsorption, leading to the increased size and improved polydispersity index of nanoparticles as well as sustained release of drug. Physicochemical characteristics such as hydrodynamic diameter, size distribution, zeta potential and morphology of nanoparticles prepared using different formulations and conditions were also determined. Based on the results, EPT was encapsulated into the prepared nanoparticles with a high drug loading capacity (5.06%) and encapsulation efficiency (94.8%) under optimal conditions. in vitro experiments demonstrated that the release of EPT from zein‐based nanoparticles was pH sensitive. When the pH level decreased from 7.4 to 5.5, the rate of drug release was considerably enhanced. The mechanism of pH‐responsive complexation in the drug encapsulation and release processes was extensively investigated. The pH‐dependent electrostatic interactions and drug state were hypothesized to affect the release profiles. Compared to the EPT‐loaded zein/PEI nanoparticles, the EPT‐loaded zein/SC nanoparticles exhibited a better drug sustained‐release profile, with a smaller initial burst release and longer release period. According to the results of in vitro cytotoxicity experiments, drug‐free nanoparticles were associated with a negligible cytotoxicity, whereas the EPT‐loaded nanoparticles displayed a high toxicity for the cancer cell line, A549. Our findings indicate that these pH‐sensitive protein‐based nanoparticles can be used as novel nanotherapeutic tools and potential antineoplastic drug carriers for cancer chemotherapy with controlled release.     

Paclitaxel‐Loaded Polylactide/Polyethylene Glycol Fibers with Long‐Term Antitumor Activity as a Potential Drug Carrier for Local Chemotherapy

Local application of anticancer agents prolongs the presence time and increases the concentration of drug in the target place and therefore may reduce serious side effects compared to drug systemic administration. The preparation of fibrous materials of polylactide (PLA) and polyethylene glycol (PEG) loaded with paclitaxel (PTX, 1 or 10 wt%) is presented. Scanning electron microscopy proves that PTX is homogeneously incorporated into the fibers. The addition of PEG of various molecular weights (6, 20, or 35 kDa) ensures the release of significantly higher amounts of hydrophobic PTX in a prolonged release time compared to the fibers containing PTX only. Present PLA‐PEG fibrous carriers can serve as a drug depot for PTX since they exhibit significant toxicity for cancer cell lines in several‐day experiment. They are promising for local recurrence therapy, where the initial release is efficient to kill tumor cells and continued release can prevent their subsequent proliferation.     

Reduction‐responsive poly (ethylene glycol)‐dexamethasone biarm conjugate and its self‐assembled nanomicelles: Preparation,physicochemical characterization,and thiol‐triggered drug release

In this study, a reduction‐responsive poly (ethylene glycol)‐dexamethasone biarm conjugate was synthesized as intracellular targeted drug delivery carriers. The hydroxyl end group of methoxy poly (ethylene glycol) (mPEG) was modified to introduce a biarm structure with bioreducible disulfide bond and amine end groups. Dexamethasone (Dex) as a nuclear targeting moiety was conjugated to the amine end groups of mPEG biarm derivatives, mPEG‐(NH₂)₂ or mPEG‐(ss‐NH₂)₂, with or without bioreducible disulfide bonds. The bioreducible and nonreducible mPEG‐Dex biarm conjugates, R‐mPEG‐Dex and N‐mPEG‐Dex, were synthesized and characterized by various analytical methods, proton nuclear magnetic resonance (¹H‐NMR), Fourier transform infraredspectroscopy (FT‐IR), dynamic light scattering (DLS), and fluorescence measurements. Amphiphilic mPEG‐Dex conjugates self‐assembled in aqueous solutions to form nanoparticles (NPs) with a size range of 130 to 150 nm, and their critical micelle concentrations (CMCs) were determined to be 12.4 and 15.3 mg/L, respectively, for bioreducible and nonreducible ones. The R‐mPEG‐Dex NPs maintained good colloidal stability in the presence of bovine serum albumin (BSA) for more than 1 week but demonstrated a significant change in colloidal stability in the presence of dithiothreitol (DTT). In DTT‐containing phosphate‐buffered saline (PBS), the bioreducible NPs showed not only reduction‐responsive destabilization with PEG shedding but also thiol‐dependent drug release profile. Our observations indicated that the R‐mPEG‐Dex NPs have a promising prospective as an efficient nanocarrier for intracellular targeted delivery of various anticancer drugs.     

Drug release and biocompatibility of self‐assembled micelles prepared from poly (ɛ‐caprolactone/glycolide)‐poly (ethylene glycol) block copolymers

A series of poly(?‐caprolactone/glycolide)‐poly(ethylene glycol) (P(CL/GA)‐PEG) diblock copolymers were prepared by ring opening polymerization of a mixture of ?‐caprolactone and glycolide using mPEG as macro‐initiator and stannous octoate as catalyst. Self‐assembled micelles were prepared from the copolymers using nanoprecipitation method. The micelles were spherical in shape. The micelle size was larger for copolymers with longer PEG blocks. In contrast, the critical micelle concentration of copolymers increased with decreasing the overall hydrophobic block length. Drug loading and drug release studies were performed under in vitro conditions, using paclitaxel as a hydrophobic model drug. Higher drug loading was obtained for micelles with longer poly(ε‐caprolactone) blocks. Faster drug release was obtained for micelles of mPEG2000 initiated copolymers than those of mPEG5000 initiated ones. Higher GA content in the copolymers led to faster drug release. Moreover, drug release rate was enhanced in the presence of lipase from Pseudomonas sp., indicating that drug release is facilitated by copolymer degradation. The biocompatibility of copolymers was evaluated from hemolysis, dynamic clotting time, and plasma recalcification time tests, as well as MTT assay and agar diffusion test. Data showed that copolymer micelles present outstanding hemocompatibility and cytocompatibility, thus suggesting that P(CL/GA)‐PEG micelles are promising for prolonged release of hydrophobic drugs.     

Light and pH Dual‐Degradable Triblock Copolymer Micelles for Controlled Intracellular Drug Release

A novel amphiphilic ABA‐type triblock copolymer poly(ethylene glycol)‐b‐poly(ethanedithiol‐alt‐nitrobenzyl)‐b‐poly(ethylene glycol) (PEG‐b‐PEDNB‐b‐PEG) is successfully prepared by sequential thiol‐acrylate Michael addition polymerization in one pot. PEG‐b‐PEDNB‐b‐PEG is designed to have light‐cleavable o‐nitrobenzyl linkages and acid‐labile β‐thiopropionate linkages positioned repeatedly in the main chain of the hydrophobic block. The light and pH dual degradation of PEG‐b‐PEDNB‐b‐PEG is traced by gel permeation chromatography (GPC). Such triblock copolymer can self‐assemble into micelles, which can be used to encapsulate anticancer drug doxorubicin (DOX). Because of the different degradation chemistry of o‐nitrobenzyl linkages and β‐thiopropionate linkages, DOX can be released from the micelles by two different manners, i.e., light‐induced rapid burst release and pH‐induced slow sustained release. Confocal laser scanning microscopy (CLSM) results indicated that DOX‐loaded micelles exhibited faster drug release in A549 cells after UV irradiation. Furthermore, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) results show that the DOX‐loaded micelles under UV light degradation exhibit better anticancer activity against A549 cells than that of the nonirradiated ones.

     

In vitro study on the drug release behavior from Polylactide‐based blend matrices

In this paper, several drug carriers were fabricated to release the hydrophilic 5‐fluorouracil (5‐Fu), such as blend of polylactide (PLA) with different molecular weights and blends of PLA with polycaprolactone (PCL) or poly(ethylene glycol) (PEG). The controlled release devices were processed into tablets containing 12.5 wt% of 5‐Fu, and the in vitro release studies were carried out under pH 7.4 at 37 ± 1 °C. The degradation of all the drug carriers were performed under the same conditions, parameters that changes of inherent viscosity, weight loss and water sorption were determined at predetermined time intervals with degradation. To inspect the morphology of the PLA‐based blends and its affect on the 5‐Fu release behavior thereof, scanning electron microscopy (SEM) and X‐ray diffraction techniques were applied. As a result, the two‐phasic release behavior of homo‐PLA was significantly ameliorated in all the cases by the initial time lag period being eliminated or shortened. And a linear 5‐Fu release behavior was obtained from blend of PLAs with different molecular weights. Copyright © 2002 John Wiley & Sons, Ltd.     

Electropolymerization of layer‐by‐layer precursor polymer films

The layer‐by‐layer (LbL) self‐assembly has been used to fabricate polymer thin films on any solid substrates. The multilayer polymer thin films are constructed by alternating adsorption of anionic and cationic polymers. Polyelectrolyte multilayer ultrathin films containing anionic poly[2‐(thiophen‐3‐yl)ethyl methacrylate‐co‐methacrylic acid]; P(TEM‐co‐MA) and cationic poly[4‐(9H‐carbazol‐9‐yl)‐N‐butyl‐4‐vinyl pyridium bromide]; P4VPCBZ, were fabricated. The growth of multilayer ultrathin films was followed by UV–Vis absorption spectrophotometer and surface plasmon resonance spectroscopy (SPR). The deposition of P(TEM‐co‐MA)/P4VPCBZ as multilayer self‐assembled ultrathin films regularly grow which showed linear growth of absorbance and thickness with increasing the number of layer pair. Cross‐linking of the layers was verified by cyclic voltammetry (CV), UV–Vis spectrophotometry and electrochemical surface plasmon resonance (EC‐SPR) spectroscopy with good electro‐copolymerizability. This was verified by spectroelectrochemistry. The SPR angular‐reflectivity measurement resulted in shifts to a higher reflectivity according to the change in the dielectric constant of the electropolymerized film. Copyright © 2011 John Wiley & Sons, Ltd.     

Stimuli‐responsive micelles of amphiphilic AMPS‐b‐AAL copolymers in layer‐by‐layer films

Aqueous reversible addition‐fragmentation chain transfer polymerization was used to synthesize poly(N‐[3‐(dimethylamino)propyl]acrylamide) (PDMAPA) cationic homopolymers and micelle‐forming, pH‐responsive, amphiphilic diblock copolymers of poly(sodium 2‐acrylamido‐2‐methyl‐1‐propanesulfonate‐block‐N‐acryloyl‐L ‐alanine) (P(AMPS‐b‐AAL)). At low pH, the AAL blocks are protonated rendering them hydrophobic, whereas the AMPS blocks remain anionically charged because of the pendant sulfonate groups. Self‐assembly results in core–shell micelles consisting of hydrophobic cores of AAL and negatively charged shells of AMPS. Using solutions of these micelles with anionic coronas and of the cationic homopolymer PDMAPA, layer‐by‐layer (LbL) films were assembled at low pH, maintaining the micelle structures. Several block copolymers with varying AMPS and AAL block lengths were synthesized and used in the formation of LbL films. The thickness and morphology of the films were examined using ellipsometry and atomic force microscopy. The stimuli‐responsive behavior can be triggered by submersion of the film in water at neutral pH to disrupt the micelles. This behavior was monitored by observing the decrease in film thickness and alteration of the film morphology. The micelles were also loaded with a model hydrophobic compound, pyrene, and incorporated into LbL films. The release of pyrene from the films was monitored by fluorescence spectroscopy at varying pH values (1, 3, 5, and 7). As the pH of the solution increases, the rate of release increases. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Amphiphilic block poly(propylene carbonate)‐block‐allyloxypolyethyleneglycol copolymer based shell cross‐linked micelles for controlled release of drug

Amphiphilic block poly(propylene carbonate)‐block‐allyloxypolyethyleneglycol (PPC‐b‐APEG) copolymer was synthesized by the click chemistry, and its structure were characterized. PPC‐b‐APEG can self‐assemble into micelles without emulsifier in water. Shell cross‐linked micelles were obtained by the reaction of the allyloxy groups, which were exposed on the outer of the PPC‐b‐APEG micelles, and N‐vinylpyrrolidone (NVP). The morphology and size of the micelles before and after cross‐link reactions were characterized. The research result shows that the shell cross‐linking could improve the stability of micelles. The particle size of uncross‐linked micelle was about 800 nm. The size of cross‐linked micelles increased with increasing amount of cross‐linking degree. To better evaluate the release behavior of PPC‐b‐PEG copolymer, doxorubicin (DOX)‐loaded micelles were synthesized using DOX as the model drug. Results showed that the DOX releasing rate decreased with increasing of NVP. The shell cross‐linking do decrease the burst release behaviours of DOX and reduce the DOX release rate.     

Block copolymer composition drives function of self‐assembled nanoparticles for delivery of small‐molecule cargo

Nanoparticles are useful for the delivery of small molecule therapeutics, increasing their solubility, in vivo residence time, and stability. Here, we used organocatalytic ring opening polymerization to produce amphiphilic block copolymers for the formation of nanoparticle drug carriers with enhanced stability, cargo encapsulation, and sustained delivery. These polymers comprised blocks of poly(ethylene glycol) (PEG), poly(valerolactone) (PVL), and poly(lactide) (PLA). Four particle chemistries were examined: (a) PEG‐PLA, (b) PEG‐PVL, (c) a physical mixture of PEG–PLA and PEG–PVL, and (d) PEG–PVL–PLA tri‐block copolymers. Nanoparticle stability was assessed at room temperature (20 °C; pH = 7), physiological temperature (37 °C; pH = 7), in acidic media (37 °C; pH = 2), and with a digestive enzyme (lipase; 37 °C; pH = 7.4). PVL‐based nanoparticles demonstrated the highest level of stability at room temperature, 37 °C and acidic conditions, but were rapidly degraded by lipase. Moreover, PVL‐based nanoparticles demonstrated good cargo encapsulation, but rapid release. In contrast, PLA‐based nanoparticles demonstrated poor stability and encapsulation, but sustained release. The PEG–PVL–PLA nanoparticles exhibited the best combination of stability, encapsulation, and release properties. Our results demonstrate the ability to tune nanoparticle properties by modifying the polymeric architecture and composition. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1322–1332     

Synthesis of an esterase‐sensitive degradable polyester as facile drug carrier for cancer therapy

Polyethylene glycol (PEG) is widely used as a carrier to improve the pharmaceutical properties of drugs with low molecular weight. However, PEG has few functional groups (usually two) for drug conjugation and the resulting low drug content (1–2%) has hampered its clinical applications. For this study, we synthesized biodegradable poly(ethylene glycol‐co‐anhydride). This polyester‐based polymer possesses multiple carboxylic acid groups that can be used as facile drug carriers. Two anticancer drugs, camptothecin (CPT) and doxorubicin (DOX) were loaded into the carrier and their releasing properties and in vitro anticancer activities were studied. The polymer–drug conjugates exhibited esterase‐promoted degradation and drug release. Their cytotoxicity against the human ovarian cancer cell line SKOV‐3 was comparable to unconjugated drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 507–515     

Flower‐Like Hierarchically Nanostructured Hydroxyapatite Hollow Spheres: Facile Preparation and Application in Anticancer Drug Cellular Delivery

Flower‐like nanostructured hydroxyapatite hollow spheres (NHHS) assembled with nanosheets with a hierarchical morphology are fabricated by a rapid microwave‐assisted hydrothermal route. The presence and concentration of block copolymer poly(lactide)‐block‐poly(ethylene glycol) (PLA–PEG) are important parameters for the formation of the hollow structure. The possible formation mechanism of NHHS is proposed. The NHHS are explored as anticancer drug carriers for cellular delivery of mitoxantrone (MIT). The MIT‐loaded NHHS exhibit sustained‐drug‐release behavior in vitro and the intracellular drug‐distribution tests indicate that the MIT loaded in NHHS carriers can enter the cells efficiently. The experiments also show that the NHHS have a good biocompatibility, and therefore, they are promising anticancer drug carriers in cancer chemotherapy.     

Biocompatibility evaluation of self‐assembled micelles prepared from poly(lactide‐co‐glycolide)‐poly(ethylene glycol) diblock copolymers

In this work, a series of PLGA‐PEG diblock copolymers were synthesized by ring‐opening polymerization of L‐lactide and glycolide using mPEG as macroinitiator and stannous octoate as catalyst. Spherical micelles were obtained from the various copolymers by using co‐solvent evaporation method. The biocompatibility of micelles was evaluated with the aim of assessing their potential in the development of drug delivery systems. Various aspects of biocompatibility were considered, including MTT assay, agar diffusion test, release of cytokines, hemolytic test, dynamic clotting time, protein adsorption in vitro, and zebrafish embryonic compatibility in vivo. The combined results revealed that the micelles present good cytocompatibility and hemocompatibility in vitro. Moreover, the cumulative effects of micelles throughout embryos developing stages have no toxicity in vivo. It is thus concluded that micelles prepared from PLGA‐PEG copolymers present good biocompatibility as potential drug carrier.