Hydrophobic Block Length Research Articles

Co-assembly of Amphiphilic Triblock Copolymers with Nanodrugs and Drug Release Kinetics in Solution.

Polymeric vesicles present great potential in disease treatment as they can be featured as a structurally stable and easily functionalized drug carrier that can simultaneously encapsulate multiple drugs and release them on-demand. Based on the dissipative particle dynamics (DPD) simulation, the drug-loaded vesicles were designed by the co-assembly process of linear amphiphilic triblock copolymers and hydrophobic nanodrugs in solvents, and most importantly, the drug release behavior of drug-loaded vesicles were intensively investigated. The drug-loaded aggregates, such as vesicles, spherical micelles, and disk-like micelles, were observed by varying the size and concentration of nanodrugs and the length of the hydrophobic block. The distribution of nanodrugs in the vesicles was intensively analyzed. As the size of the nanodrugs increases, the localization of nanodrugs change from being unable to fully wrap in the vesicle wall to the uniform distribution and finally to the aggregation in the vesicles at the fixed concentration of nanodrugs. The membrane thickness of the drug-loaded polymeric vesicle can be increased, and the nanodrugs localized closer to the center of the vesicle by increasing the length of the hydrophobic block. The nanodrugs will be released from vesicles by varying the interactions between the nanodrug and the solvent or the hydrophobic block and the solvent, respectively. We found that the release kinetics conforms to the first-order kinetic model, which can be used to fit the cumulative release rate of nanodrugs over time. The results showed that increasing the size of nanodrugs, the length of hydrophobic block, and the interaction parameters between the hydrophobic block and the solvent will slow down the release rate of the nanodrug and change the drug release process from monophasic to biphasic release model.

Thermoresponsive Water-in-Oil-in-Water Pickering Double Emulsions Stabilized with Biodegradable and Semicrystalline Poly(ethylene glycol)-b-poly(ε-caprolactone-co-δ-valerolactone) Diblock Copolymer Micelles for Controlled Release.

Water-in-oil-in-water (W/O/W) Pickering double emulsions are promising materials for the construction of carriers for water-soluble and oil-soluble molecules or drug delivery systems if the contradictive trade-off between their extreme stability and controlled release properties can be resolved. In this study, biodegradable and biocompatible poly(ethylene glycol)-b-poly(ε-caprolactone-co-δ-valerolactone) (PEG-b-PCVL) diblock copolymers with predesigned hydrophilic to hydrophobic block length ratios and nearly identical ε-caprolactone/δ-valerolactone molar ratio (8/2), were synthesized by ring-opening copolymerization. Then, they self-assembled to create semicrystalline micelles. The melting points of PEG-b-PCVL copolymers and their lyophilized micelles were within a physiological range of temperatures, as determined by differential scanning calorimetry. Water contact angle measurements provided evidence that the surface wettability of PEG-b-PCVL micelles could be tuned by the PCVL block mass fractions or temperature stimulus. Such PEG-b-PCVL micelles were employed as a single particulate stabilizer to develop Pickering double emulsions through a one-step emulsification technique. W/O/W Pickering double emulsions could be generated using relatively hydrophobic PEG-b-PCVL micelles with high mass fractions (exceeding about 89%) of PCVL blocks, and they displayed excellent long-term physical stabilities at room temperature. However, the Pickering double emulsions underwent a rapid microstructural transition into simple oil-in-water Pickering emulsions instead of complete demulsification at elevated temperature (37 °C), which was attributed to the hydrophilicity of micelles enhanced when the core-forming PCVL melted realized by temperature stimulus. Consequently, such W/O/W Pickering double emulsions stabilized solely with semicrystalline PEG-b-PCVL micelles exhibit thermal responsiveness, enabling them to release vitamin B12 encapsulated within the internal aqueous phase rapidly.

Synthesis and Evaluation of Thermoresponsive Renewable Lipid-Based Block Copolymers for Drug Delivery.

Polymeric micelle forming from self-assembly of amphiphilic macromolecules is one of the most potent drug delivery systems. Fatty acids, naturally occurring hydrophobic lipid components, can be considered as potential candidates for the fabrication of block copolymer micelles. However, examples of synthesis of responsive block copolymers using renewable fatty acids are scarce. Herein, we report the synthesis, characterization and testing of block copolymer micelles composed of a renewable fatty-acid-based hydrophobic block and thermoresponsive hydrophilic block for controlled drug delivery. The block copolymers of functionalized fatty acid and poly(N-isopropylacrylamide) (PNIPAM) were prepared via consecutive microwave-assisted reversible addition fragmentation chain transfer (RAFT) polymerization. The block copolymers with variable hydrophobic block length self-assembled in aqueous media and formed spherical nanoparticles of ~30 nm with low critical micelle concentration (CMC). To demonstrate the proof-of-concept, carbamazepine (CBZ) was used as a hydrophobic model drug to evaluate the performance of these micelles as nanocarriers. The in vitro drug release tests were carried out below (25 °C) and above (37 °C) the lower critical solution temperature (LCST) of the block copolymer. The drug release showed obvious temperature-triggered response and an accelerated drug release at 37 °C.

In situ photo‐crosslinked hydrogels prepared from acrylated 4‐arm‐poly(ethylene glycol)‐poly(ε‐caprolactone) block copolymers for local cancer therapy

AbstractAmphiphilic block copolymers were synthesized by ring‐opening polymerization of ε‐caprolactone (ε‐CL) using 4‐arm poly(ethylene glycol) (4aPEG) as macroinitiator. 4aPEG and 4aPEG‐PCL copolymers were end functionalized by introducing acrylic groups, and characterized using NMR, GPC, FT‐IR and DSC analyses. Photo‐crosslinked hydrogels were prepared by irradiation of acrylated polymer solutions under visible light (405 nm), using lithium phenyl‐2,4,6‐trimethylbenzoy‐lphosphinate (LAP) as a photoinitiator. In situ gelation was achieved by subcutaneous injection of LAP containing copolymer solution into the abdomen of mice, followed by exposure to visible light. The hydrogels exhibit highly porous structure, high swelling up to 3300%, and excellent biocompatibility. The swelling ratio decreases with increase of poly(ɛ‐caprolactone) (PCL) block length and polymer concentration of hydrogels. Doxorubicin hydrochloride (DOX·HCl) was loaded in hydrogels by soaking dried gel in a DOX solution. The drug loading efficiency is dependent on the swelling performance, reaching a maximum of 94.3%. In vitro drug release studies showed a burst release for the first 6 h, followed by a slower release up to 82% at 28 days. The release rate decreased with increase of hydrophobic block length or polymer concentration of hydrogels. Higher anti‐cancer activity on A549 lung cancer cells was obtained for hydrogels with higher drug concentration, and shorter PCL block length. Therefore, 4aPEG‐PCL hydrogels with outstanding biocompatibility, in situ gelation and prolonged drug release could be very promising for long‐term local cancer therapy.

Sulfonated poly(phenylene-co-arylene ether sulfone) multiblock membranes for application in high-performance fuel cells

Sulfonated multiblock poly(phenylene- co -arylene ether sulfone) (SmPPES) membranes for application in polymer electrolyte membrane fuel cells are prepared via Colon's Nickel catalyzed cross-coupling reaction. Their chemical stabilities and proton transport abilities are examined as functions of ion-exchange capacity (IEC) and hydrophilic (sulfonated phenylene) and hydrophobic (arylene ether sulfone) block lengths. The membranes show well-defined phase separation and proton conductivities comparable to or exceeding that of a reference Nafion membrane. Block length is positively correlated with conductivity and oxidative stability; SmPPES10–2.0 showed conductivities of 0.11 and 0.13 S/cm in water at 25 °C and 80 °C (90% relative humidity), respectively, and those of SmPPES5-2.0 were 0.10 and 0.11 S/cm, respectively. The SmPPES membrane oxidative stabilities (determined by Fenton's oxidative tests and peroxide exposure tests) are superior to those of conventional poly(arylene ether) membranes because of their sulfonated phenylene blocks. At 80 °C and 100% relative humidity, the optimal SmPPES membrane (IEC = 2.5 meq/g) delivers a current density of 1.5 A/cm 2 at 0.6 V (hydrogen/air) and a high-frequency resistance of 38 mΩ cm 2 , outperforming the reference Nafion NR211 membrane. This control over sulfonated phenylene and ether sulfone hydrophobic blocks provides new insight into designing high-performance polymer electrolyte membranes. • Sulfonated multiblock poly(phenylene- co -arylene ether sulfone) (SmPPES) membranes. • SmPPES membranes prepared using a combination of meta - and para -phenylene. • SmPPES membranes outperformed sulfonated poly(arylene ether sulfone) copolymers. • Fuel cell performance of optimal SmPPES membrane exceeded that of a Nafion membrane. • Flexible phenylene block copolymers comparable to perfluorosulfonic acid membranes.

One-Pot Synthesis of Oxidation-Sensitive Supramolecular Gels and Vesicles.

Polypeptide-based nanoparticles offer unique advantages from a nanomedicine perspective such as biocompatibility, biodegradability, and stimuli-responsive properties to (patho)physiological conditions. Conventionally, self-assembled polypeptide nanostructures are prepared by first synthesizing their constituent amphiphilic polypeptides followed by postpolymerization self-assembly. Herein, we describe the one-pot synthesis of oxidation-sensitive supramolecular micelles and vesicles. This was achieved by polymerization-induced self-assembly (PISA) of the N-carboxyanhydride (NCA) precursor of methionine using poly(ethylene oxide) as a stabilizing and hydrophilic block in dimethyl sulfoxide (DMSO). By adjusting the hydrophobic block length and concentration, we obtained a range of morphologies from spherical to wormlike micelles, to vesicles. Remarkably, the secondary structure of polypeptides greatly influenced the final morphology of the assemblies. Surprisingly, wormlike micellar morphologies were obtained for a wide range of methionine block lengths and solid contents, with spherical micelles restricted to very short hydrophobic lengths. Wormlike micelles further assembled into oxidation-sensitive, self-standing gels in the reaction pot. Both vesicles and wormlike micelles obtained using this method demonstrated to degrade under controlled oxidant conditions, which would expand their biomedical applications such as in sustained drug release or as cellular scaffolds in tissue engineering.

Smart block copolymers as fluorescence chemosensors of copper ions with high detection limit

Stimuli-responsive block copolymers were synthesized to detect copper ions with high limit based on a fluorescence quenching mechanism. For this purpose, poly(7-acryloyloxy 4-methylcoumarin-r-methyl methacrylate)-b-poly(dimethylaminoethyl methacrylate) in three different block ratios was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization. Successful synthesis of the block copolymers was confirmed by Fourier-transformed infrared and proton nuclear magnetic resonance spectroscopies. Self-assembly of the copolymers in aqueous media resulted in formation of micellar structures, as confirmed by transmission electron microscopy images and also estimated form the hydrophilic fraction of the block copolymers. Micellar size and dispersity were studied by dynamic light scattering in different conditions. In addition, dimerization kinetics of the coumarin molecules in the micellar assemblies were studied by ultraviolet–visible spectroscopy. The sample with higher molar ratio of CMA in the hydrophobic block and shorter length of PDMAEMA in the hydrophilic block showed faster dimerization reaction. The micellar assemblies formed from all the copolymers were used to sense potassium, calcium, and copper cations. All the self-assembled structures showed high sensitivity to detect copper cation, by quenching their fluorescence intensity. The copolymer sample with the highest ratio of PDMAEMA/CMA in the chain structure has the highest detection limit of 0.002 ppm for copper ion.

Correlation between the composition of PLA-based folate targeted micelles and release of phosphonate derivative of betulin

There are increasing numbers of developed nanocarriers for anticancer drug delivery in the aim to avoid side effects of the conventional chemotherapy. Filomicelles with folic acid (FA) as a targeting moiety are a novel approach that can potentially maximize therapeutic efficacy while minimizing side effects. The aim of this study was to analyze the influence of composition of PLA-based micelles functionalized with folic acid on their drug encapsulation and release properties as well as cytotoxic activity against cancer cells. Micelles were obtained from combination of poly (l-lactide)-Jeffamine-folic acid (PLA-Jeff-FA) and poly (l-lactide)-poly (ethylene glycol) (PLA-PEG) or poly (l-lactide)-poly (ethylene glycol)-folic acid and PLA-PEG. E−29-diethoxyphosphoryl-28-O-propynoylbetulin as an anticancer agent was encapsulated into micelles. The in vitro biocompatibility of drug-free micelles was confirmed as well as cytotoxicity of E−29-diethoxyphosphoryl-28-O-propynoylbetulin loaded micelles against FR-positive SK-BR-3 cells. The micelles provided a release of an active agent for over 260 h. However, the micelles characterized differences in morphology, drug loading and release properties. The hydrophobic block length has been identified as a factor that may be used to control inter- and intramolecular interactions and, in consequence, micelle's properties, e.g. drug encapsulation efficiency and release rate.

PH/enzyme/light triple‐responsive vesicles from lysine‐based amphiphilic diblock copolymers

AbstractWe report the synthesis of pH‐ and enzyme‐responsive amphiphilic diblock copolymers through reversible addition‐fragmentation chain transfer polymerization of a lysine‐derived methacrylate monomer comprising p‐nitrobenzyl carbamate (pNBC) functionality using a poly(ethylene glycol)‐modified macro‐chain transfer agent. Depending on the hydrophobic block length, the diblock copolymers self‐assemble to form spherical micelles, wormlike micelles, and bilayered vesicles in the aqueous solution. The responsive behaviors of the polymeric vesicles to pH, enzyme, and light are investigated in detail. As the pH lowers to pH 5.0, the polymeric vesicles undergo a morphological transition from vesicles to spherical micelles. In the presence of nitroreductase and a cofactor NADH, the decomposition of pNBC releases the ε‐NH2 of the lysine moiety and hence induces the generation of the vesicles with crosslinked membranes at pH 7.4. Moreover, owing to the degradation of pNBC moiety under UV irradiation, the polymeric vesicles also demonstrate a photo‐responsive feature. As the irradiation time prolongs, it is observed a light‐triggered morphological transition from vesicles to wormlike micelles with network‐like structures.

Application of poly(amidoamine) dendrimer as transfer agent to synthesize poly(amidoamine)-b-poly(methyl acrylate) amphiphilc block copolymers: Self-assembly in aqueous media and drug delivery

Herein, second generation cystamine-cored poly(amidoamine) (PAMAM) dendrimer has been synthesized and used as transfer agent in atom transfer radical polymerization (ATRP) of poly(methyl acrylate) (PMA). Transfer reaction to dendrimer has been resulted in synthesis of PAMAM-b-PMA block copolymers with different degree of polymerization of PMA block. Synthesized block copolymers have been self-assembled in aqueous media to prepare cubic/hexagonal and spherical supramolecular structures with nanoscale particle size. Finally, the behavior of drug release from supramolecular structures as nanocarriers of the anticancer drug, doxorubicin (DOX), has been investigated under different conditions. Results showed that in block copolymers with shorter length of hydrophobic block, drug loading capacity was increased due to predominant interactions between dendrimer and drug molecules. Higher hydrophobic block length led to higher cumulative release of drug due to presence of hydrophobic interactions between PMA block and DOX molecules. Moreover, nanocarriers showed significant drug release in acidic media whereas no remarkable release was observed at pH = 7.4.

Poly(Ethylene Glycol)-b-Poly(D,L-Lactide) Nanoparticles as Potential Carriers for Anticancer Drug Oxaliplatin.

Nanoparticles based on biocompatible methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG113-b-P(D,L)LAn) copolymers as potential vehicles for the anticancer agent oxaliplatin were prepared by a nanoprecipitation technique. It was demonstrated that an increase in the hydrophobic PLA block length from 62 to 173 monomer units leads to an increase of the size of nanoparticles from 32 to 56 nm. Small-angle X-ray scattering studies confirmed the “core-corona” structure of mPEG113-b-P(D,L)LAn nanoparticles and oxaliplatin loading. It was suggested that hydrophilic oxaliplatin is adsorbed on the core-corona interface of the nanoparticles during the nanoprecipitation process. The oxaliplatin loading content decreased from 3.8 to 1.5% wt./wt. (with initial loading of 5% wt./wt.) with increasing PLA block length. Thus, the highest loading content of the anticancer drug oxaliplatin with its encapsulation efficiency of 76% in mPEG113-b-P(D,L)LAn nanoparticles can be achieved for block copolymer with short hydrophobic block.

From spherical compartments to polymer films: exploiting vesicle fusion to generate solid supported thin polymer membranes.

Solid supported polymer membranes as scaffold for the insertion of functional biomolecules provide the basis for mimicking natural membranes. They also provide the means for unraveling biomolecule-membrane interactions and engineering platforms for biosensing. Vesicle fusion is an established procedure to obtain solid supported lipid bilayers but the more robust polymer vesicles tend to resist fusion and planar membranes rarely form. Here, we build on vesicle fusion to develop a refined and efficient way to produce solid supported membranes based on poly(dimethylsiloxane)-poly(2-methyl-2-oxazoline) (PMOXA-b-PDMS-b-PMOXA) amphiphilic triblock copolymers. We first create thiol-bearing polymer vesicles (polymersomes) and anchor them on a gold substrate. An osmotic shock then provokes polymersome rupture and drives planar film formation. Prerequisite for a uniform amphiphilic planar membrane is the proper combination of immobilized polymersomes and osmotic shock conditions. Thus, we explored the impact of the hydrophobic PDMS block length of the polymersome on the formation and the characteristics of the resulting solid supported polymer assemblies by quarz crystal microbalance with dissipation monitoring (QCM-D), atomic force microscopy (AFM) and spectroscopic ellipsometry (SE). When the PDMS block is short enough, attached polymersomes restructure in response to osmotic shock, resulting in a uniform planar membrane. Our approach to rapidly form planar polymer membranes by vesicle fusion brings many advantages to the development of synthetic planar membranes for bio-sensing and biotechnological applications.

Probing Thermoresponsive Polymerization-Induced Self-Assembly with Variable-Temperature Liquid-Cell Transmission Electron Microscopy

Summary We directly initiate and visualize the formation of polymeric nanomaterials via variable-temperature liquid-cell transmission electron microscopy (VT-LCTEM). With temperature control in the liquid cell, reversible addition-fragmentation chain transfer polymerization was thermally initiated, leading to the formation of amphiphilic block copolymers that assemble upon dispersion polymerization-induced self-assembly (PISA). In combination with traditional ex situ analyses, VT-LCTEM enabled not only the characterization of the nanoparticles in situ but also the observation of a thermal phase transition. Critically, because these assemblies form from thermoresponsive components, any temperature changes during sample preparation and analysis can alter morphologies, necessitating direct in situ characterization of reaction progression. We believe that the findings and the technique described herein will lead to unprecedented possibilities for the development and characterization of self-organizing soft matter.

Strategy of “Block Blends” to Generate Polymeric Thermogels versus That of One-Component Block Copolymer

Polymer alloys are usually classified into polymer blends and block copolymers. Herein, we combine the two alloying strategies to endow materials with a thermoinduced sol–gel transition. Our system is composed of two amphiphilic block copolymers in water, and we suggest terming it a “block blend.” A series of “computer experiments” by dynamic Monte Carlo simulations were carried out to verify our idea of “block blends” and revealed the mechanism of the underlying physical gelation. A thermogel was achieved after blending two amphiphilic block copolymers with different lengths of hydrophobic and hydrophilic blocks and thus different extents of the hydrophilicity–hydrophobicity balances, in which one copolymer could otherwise always flow and the other could be insoluble in water prior to the blending. It is thus interesting that “block blends” can make non-thermogellable copolymers useful in thermogellable systems. We also examined “averaged” copolymers which shared the same composition with the block blends, and our comparative studies illustrated that the block blends impregnated richer physics. A thermogel has a percolated micelle network. Although the amphiphilicity of the copolymer determines the micelle formation, the spatial heterogeneity of two copolymers is crucial in further formation of the network, where semibald micelles are connected by hydrophobic channels rich in the relatively more hydrophobic copolymer. The block-blend strategy paves a way to generate an intelligent material, in particular, a biomaterial by hierarchical self-assembly.

Biotin-decorated all-HPMA polymeric micelles for paclitaxel delivery

To avoid poly(ethylene glycol)-related issues of nanomedicines such as accelerated blood clearance, fully N-2-hydroxypropyl methacrylamide (HPMAm)-based polymeric micelles decorated with biotin for drug delivery were designed. To this end, a biotin-functionalized chain transfer agent (CTA), 4-cyano-4-[(dodecylsulfanylthiocarbonyl)-sulfanyl]pentanoic acid (biotin-CDTPA), was synthesized for reversible addition–fragmentation chain-transfer (RAFT) polymerization. Amphiphilic poly(N-2-hydroxypropyl methacrylamide)-block-poly(N-2-benzoyloxypropyl methacrylamide) (p(HPMAm)-b-p(HPMAm-Bz)) with molecular weights ranging from 8 to 24 kDa were synthesized using CDTPA or biotin-CDTPA as CTA and 2,2′-azobis(2-methylpropionitrile) as initiator. The copolymers self-assembled in aqueous media into micelles with sizes of 40–90 nm which positively correlated to the chain length of the hydrophobic block in the polymers, whereas the critical micelle concentrations decreased with increasing hydrophobic block length. The polymer with a molecular weight of 22.1 kDa was used to prepare paclitaxel-loaded micelles which had sizes between 61 and 70 nm, and a maximum loading capacity of around 10 wt%. A549 lung cancer cells overexpressing the biotin receptor, internalized the biotin-decorated micelles more efficiently than non-targeted micelles, while very low internalization of both types of micelles by HEK293 human embryonic kidney cells lacking the biotin receptor was observed. As a consequence, the paclitaxel-loaded micelles with biotin decoration exhibited stronger cytotoxicity in A549 cells than non-targeted micelles. Overall, a synthetic pathway to obtain actively targeted poly(ethylene glycol)-free micelles fully based on a poly(HPMAm) backbone was established. These polymeric micelles are promising systems for the delivery of hydrophobic anticancer drugs.

Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization‐Induced Self‐Assembly

AbstractHerein, we report the photoinitiated polymerization‐induced self‐assembly (photo‐PISA) of spherical micelles consisting of proapoptotic peptide–polymer amphiphiles. The one‐pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL−1) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide‐functionalized nanoparticles imbued the proapoptotic “KLA” peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo‐PISA in the large‐scale synthesis of functional, proteolytically resistant peptide–polymer conjugates for intracellular delivery.

Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly.

Herein, we report the photoinitiated polymerization-induced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide-polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL-1 ) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide-functionalized nanoparticles imbued the proapoptotic "KLA" peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide-polymer conjugates for intracellular delivery.

Drug-Directed Morphology Changes in Polymerization-Induced Self-Assembly (PISA) Influence the Biological Behavior of Nanoparticles.

The effect of the hydrophobic block length on the morphologies of polymerization-induced self-assembled (PISA) nanoparticles is well understood. However, the influence of drug loading on the phase morphology of the nanoparticles during the PISA process, and the resulting biological function of PISA nanoparticles, has barely been investigated. In this work, we show that the addition of a drug, curcumin, during the PISA process shifts the phase diagram toward different morphologies. The PISA system was based on hydrophilic poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC), which was chain extended with hydrophobic methyl methacrylate (MMA) in various concentrations of curcumin. According to transmission electron microscopy, the presence of curcumin led to the transition of, for example, worms to polymersome and micelles to worms analysis. To understand the interaction between polymer particles and drug, small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), and fluorescence lifetime measurements were carried out. These measurements show that curcumin is predominantly located in the core in the case of micelles and worms while it is found in the shell of polymersomes. The change in morphology influences the cellular uptake by MCF-7 cells and the movement of the particles in multicellular cancer spheroids (3D model). With the increasing amount of drug, the cellular uptake of micelles and worms was enhanced with the increasing grafting density of MPC chains, which contrasts the decreasing cellular uptake in the higher drug-loaded polymersomes due to the lower shell hydration.

Synthesis and Self-Assembly of Hydroxypropyl Methyl Cellulose-block-Poly(ε-caprolactone) Copolymers as Nanocarriers of Lipophilic Drugs

A series of amphiphilic diblock copolymers with different hydrophilic and hydrophobic block lengths were synthesized by reductive amination of hydroxypropyl methyl cellulose (HPMC) and end-function...

Enhanced Anti‐Bacterial Activity of Non‐Antibacterial Drug Candesartan Cilexetil by Delivery through Polymeric Micelles

AbstractCandesartan Cilexetil (CC) is a prodrug of candesartan and an angiotensin II receptor antagonist. It is used as a drug for different diseases like myocardial infarction, hypertension, and heart failure. The applicability of CC is impeded due to its poor water solubility, low permeability, and low bioavailability. This study is targeted to improve the efficacy and bioavailability of CC by its delivery through MeO‐PEO5K‐PCL micelles. The effect of length of hydrophobic block (PCL) on size of the micelles, drug encapsulation efficiency, and drug release behavior is evaluated. MeO‐PEO5K‐PCL based micelles were prepared by solvent evaporation method. The size of PMs was determined by dynamic light scattering, morphology by atomic force microscopy, and critical micelles concentration by fluorescence method. Encapsulation efficiency and drug release behaviors of MeO‐PEO5K‐PCL based PMs were evaluated by UV‐visible spectroscopy and dispersion method, respectively. The size of micelles increased and drug release rate decreased with increase in the length of PCL block. Maximum encapsulation efficiency of 96.42 % for CC is achieved with ABCs having equal PEO and PCL block lengths. A comparison of antibacterial activity of CC in pure form and encapsulated in PMs against MRSA is conducted. The MIC50 for CC loaded PMs has decreased to more than half in comparison to pure drug. AFM based morphological analysis also confirmed the decrease in MIC50 by delivery through PMs.