Surfactant chain length effects on nanoparticles of biodegradable polymers for targeted drug delivery

Folic acid‐conjugated nanoparticles (NPs) of biodegradable polymer poly(lactic‐co‐glycolic acid) (PLGA), which were emulsified by long‐chain D ‐α‐tocopheryl polyethylene glycol succinate (vitamin E TPGS or simply TPGS) for targeted delivery of anticancer drugs, are prepared. The NPs were characterized for their size and size distribution, surface morphology, surface charge, drug encapsulation efficiency, and surface chemistry. The cellular uptake and the cytotoxicity of the drug‐loaded PLGA NPs were assessed in vitro with MCF7 breast cancer cells in close comparison with the corresponding Short‐chain TPGS (TPGS2k)‐coated PLGA NPs and the original drug. The long‐chain TPGS 2000 (TPGS2k)‐emulsified PLGA NPs showed great advantages over the short‐chain TPGS 1000 (TPGS1k)‐emulsified and the nude PLGA NPs. The folic acid‐conjugated TPGS2k‐emulsified PLGA NPs showed significant advantages in cellular uptake and therapeutic effects in vitro. The IC₅₀ value showed 90.4% less than that of the original drug. © 2012 American Institute of Chemical Engineers AIChE J, 2012     

Chitosan/OA nanoparticle as delivery system for celecoxib: Parameters affecting the particle size,encapsulation, and release

Self‐assembled nanoparticles prepared from amphiphilic chitosan/oleic acid (Ch/OA) have shown antibacterial activity and potential application as a carrier for hydrophobic anticancer drugs. In this study, a low molecular weight chitosan was modified with oleic acid obtaining a degree of substitution (DS) of 12%. The critical aggregation concentration (CAC) of the Ch/OA polymer obtained (0.025 mg mL^?1) is lower in comparison with some systems of chitosan‐fatty acids. The self‐assembled Ch/OA nanoparticle size was optimized by changing polymer concentration, solvent, method, and time of homogenization to obtain particles with sizes around 300 nm and positive zeta potential. The drug loading about 7 μg mL^?1 and encapsulation efficiency of 75.8 ± 3.6% for Celecoxib was affected by the drug concentration. In vitro release behavior performed in (PBS, pH 7.4) and MES buffer (pH 6) indicated a pH‐dependent drug release behavior. The self‐assembled systems show stability during 4 weeks after the encapsulation of the hydrophobic drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44472.     

Temperature/pH dual responsive microgels of crosslinked poly(N‐vinylcaprolactam‐co‐undecenoic acid) as biocompatible materials for controlled release of doxorubicin

Undecenoic acid functionalized thermo/pH responsive microgels, poly(N‐vinylcaprolactam‐co‐undecenoic acid) [poly(VCL‐co‐UA)], were synthesized by precipitation emulsion copolymerization. The microgels exhibit reversible thermo/pH responsive phase transition behavior, which can be tuned by varying the monomer feed ratio. The lower critical solution temperatures (LCSTs) of the materials are close to body temperature. As a result, when temperatures rise above ca. 37°C, a rapid thermal gelation process occurs, accompanied by a phase transition, resulting in expulsion of encapsulated compound. In vitro experiment evaluated its applicability as a drug carrier for controlled release of an anticancer agent (doxorubicin) and showed that the drug encapsulation efficiency (EE), releasing rate, and kinetics are dependent on the temperature and pH value as expected. Minimal cytotoxicity of the microgels was observed by a cytotoxicity assay using 3T3 fibroblast cells. Our finding suggests that the poly(VCL‐co‐UA) based microgels may be considered a promising candidate for temperature or pH‐controlled delivery of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41146.     

Retention of Eucalyptol,a Natural Volatile Insecticide,in Delivery Systems Based on Hydroxypropyl‐β‐Cyclodextrin and Liposomes

Eucalyptol (Euc) is a natural monoterpene with insecticide effects. Being highly volatile and sensitive to ambient conditions, its encapsulation would enlarge its application. Euc‐loaded conventional liposomes (CL), cyclodextrin/drug inclusion complex, and drug‐in‐cyclodextrin‐in‐liposomes (DCL) are prepared to protect Euc from degradation, reduce its evaporation, and provide its controlled release. The liposomal suspension is freeze‐dried using hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as cryoprotectant. The liposomes are characterized before and after freeze‐drying. The effect of Euc on the fluidity of liposomal membrane is also examined. A release study of Euc from delivery systems, in powder and reconstituted forms, is performed by multiple head extraction at 60 °C after 6 months of storage at 4 °C. CL and DCL suspensions are homogeneous, show nanometric vesicles size, spherical shape, and negative surface charge before and after freeze‐drying. Moreover, HP‐β‐CD does not affect the fluidity of liposomes. CL formulations present a weak encapsulation for Euc. The loading capacity of eucalyptol in DCL is 38 times higher than that in CL formulation. In addition, freeze‐dried DCL and HP‐β‐CD/Euc inclusion complex show a higher retention of eucalyptol than CL delivery system. Both carrier systems HP‐β‐CD/Euc and Euc‐loaded DCL decrease Euc evaporation and improve its retention. Practical Applications: Eucalyptol is a natural insecticide. It is highly volatile and poorly soluble in water. To enlarge its application, its encapsulation in three delivery systems (conventional liposomes, cyclodextrin/drug inclusion complex, combined system composed of cyclodextrin inclusion complex and liposome) is studied. In this paper it is proved that cyclodextrin/eucalyptol inclusion complex and eucalyptol‐in‐cyclodextrin‐in‐liposome are effective delivery systems for encalyptol encapsulation, retention, and release.     

A multiple emulsion method for loading 5‐fluorouracil into a magnetite‐loaded nanocapsule: a physicochemical investigation

The preparation of 5‐fluorouracil (5‐FU) loaded poly(lactic‐co‐glycolic acid) (PLGA) biodegradable nanocapsules containing magnetite nanoparticles was studied through the modified multiple emulsion solvent evaporation method for magnetically controlled delivery of anticancer drugs. The morphology and size distribution of the prepared magnetite/PLGA nanocapsules were investigated by transmission and scanning electron microscopy. The micrographs showed that the magnetic nanocapsules were almost spherical in shape and their mean diameter was in the nanometer range with a narrow size distribution. Fourier transform infrared and ultraviolet–visible spectroscopy confirmed incorporation of 5‐FU molecules into the PLGA matrix. The magnetite content was assessed by thermogravimetric and magnetometry analysis and the results showed a magnetite content of 35 wt% with high magnetic responsivity. Magnetometry measurements showed superparamagnetic properties of the magnetic nanocapsules with a saturation magnetization of 13.7 emu g^?1. Such biodegradable magnetic nanocapsules could be considered as an appropriate choice for drug targeting. Furthermore, the influence of some important processing parameters such as PLGA concentration, initial loading of 5‐FU and poly(vinyl alcohol) concentration on drug content, encapsulation efficiency and in vitro drug release kinetics was investigated and optimized. The drug content and encapsulation efficiency of the magnetic nanocapsules were 4–7 wt% and 60%–80%, respectively, and the nanocapsules demonstrated controlled release of 5‐FU at 37 °C in a buffer solution. All samples exhibited a burst release at the initial stage and this burst release showed its close dependence on the formulation parameters. Copyright © 2012 Society of Chemical Industry     

Co‐delivery of methotrexate and doxorubicin via nanocarriers of star‐like poly(DMAEMA‐block‐HEMA‐block‐AAc) terpolymers

Combined therapy is a promising strategy for clinical cancer treatment with synergistic effects. The purpose of the work reported was to evaluate a smart nanocarrier for co‐delivery of doxorubicin (DOX) and methotrexate (MTX). Since star‐like nanocarriers can load a high dose of drugs with various properties, we developed star polymer nanomicelles based on poly[(2,2‐dimethylaminoethyl methacrylate)‐block‐(2‐hydroxyethyl methacrylate)‐block‐(acrylic acid)] having potential for multi‐drug delivery. The nanomicelles demonstrated high encapsulation efficiency, i.e. 97.1% for DOX and 79.5% for MTX. To this end, the star‐like terpolymers were synthesized via atom transfer radical polymerization with pentaerythritol as an initiator. The micellar properties and dual stimuli‐responsive behaviour of the terpolymers were investigated using transmission electron microscopy, field emission scanning electron microscopy and dynamic light scattering measurements, concluding that this co‐therapy offers a promising approach for cancer treatment. © 2019 Society of Chemical Industry     

Hispolon Cyclodextrin Complexes and Their Inclusion in Liposomes for Enhanced Delivery in Melanoma Cell Lines

Hispolon, a phenolic pigment isolated from the mushroom species Phellinus linteus, has been investigated for anti-inflammatory, antioxidant, and anticancer properties; however, low solubility and poor bioavailability have limited its potential clinical translation. In this study, the inclusion complex of hispolon with Sulfobutylether-β-cyclodextrin (SBEβCD) was characterized, and the Hispolon-SBEβCD Complex (HSC) was included within the sterically stabilized liposomes (SL) to further investigate its anticancer activity against melanoma cell lines. The HSC-trapped-Liposome (HSC-SL) formulation was investigated for its sustained drug delivery and enhanced cytotoxicity. The inclusion complex in the solid=state was confirmed by a Job’s plot analysis, molecular modeling, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy (SEM). The HSC-SL showed no appreciable deviation in size (<150 nm) and polydispersity index (<0.2) and improved drug encapsulation efficiency (>90%) as compared to control hispolon liposomes. Individually incorporated hispolon and SBEβCD in the liposomes (H-CD-SL) was not significant in loading the drug in the liposomes, compared to HSC-SL, as a substantial amount of free drug was separated during dialysis. The HSC-SL formulation showed a sustained release compared to hispolon liposomes (H-SLs) and Hispolon-SBEβCD liposomes (H-CD-SLs). The anticancer activity on melanoma cell lines (B16BL6) of HSC and HSC-SL was higher than in H-CD-SL and hispolon solution. These findings suggest that HSC inclusion in the HSC-SL liposomes stands out as a potential formulation approach for enhancing drug loading, encapsulation, and chemotherapeutic efficiency of hispolon and similar water insoluble drug molecules.     

Encapsulation of animal wax‐based organogels in alginate microparticles

Encapsulation of organogels is a novel perspective in the field of controlled drug delivery. This study reports encapsulation of lanolin based organogels within alginate microparticles. The microparticles were prepared by emulsification/internal gelation method. Microscopic studies suggested spherical shape of the microparticles. Fourier transform infrared, X‐ray diffraction and thermal studies confirmed the presence of organogels within the microparticles. Organogels containing microparticles showed improved drug (e.g., salicylic acid and metronidazole) entrapment efficiency. The release of the drugs from the microparticles was dependent on the pH of the dissolution medium. The release was diffusion mediated. The drug loaded microparticles showed antimicrobial activity against E. coli and B. subtilis. The preliminary study suggested that the encapsulation of the organogels may help prolonging the release of the drugs and hence may be tried as vehicles for controlled drug delivery. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40910.     

Intracellular pH‐sensitive dextran‐based micelles as efficient drug delivery platforms

As drug delivery systems, stimuli‐responsive polymer micelles hold great potential in cancer chemotherapeutics to improve therapeutic efficiency and eliminate organism adverse effects. Here, pH‐sensitive polymeric micelles based on dextran‐g‐benzimidazole were designed and used for intracellular anticancer drug delivery. The anticancer drug doxorubicin (DOX) was effectively loaded into the micelles via hydrophobic interactions. In vitro release studies demonstrated that the release of loaded DOX was greater and faster under acid conditions such as in carcinomatous areas (pH < 6.8) than in physiological conditions (pH 7.4). MTT assays and flow cytometric analyses showed that DOX‐loaded micelles had higher cellular proliferation inhibition towards HeLa and HepG2 cells than pH‐insensitive controls. These pH‐sensitive micelles with significant efficiency for intracellular drug release will be beneficial to the future of in vivo biomedical applications. © 2014 Society of Chemical Industry     

Optimized flurbiprofen cationic liposomes in situ gelling system of thermosensitive polymers for ocular delivery

A Flurbiprofen (FP) cationic liposomes in situ gelling system (CLIGS) of thermosensitive polymers was proposed; we investigated its in vitro and in vivo properties, and its potential use in ocular drug delivery was evaluated. This system, optimized via center composite design, was conceived from a combination of polymer‐ and lipid‐based delivery systems. Therefore, the system could integrate the advantages of both cationic liposomes and in situ gels and further improve the poor stability of cationic liposomes. Cationic liposomes were characterized for their particle size, shape, entrapment efficiency, ζ potential, and photograph of transmission electron microscopy. The in vitro penetration capability and precorneal retention time of the FP CLIGS were evaluated by a vertical Franz‐type cell method and γ scintigaraphy, respectively. The FP CLIGS showed an improved stability during a 30‐day storage period over than of FP cationic liposomes. In conclusion, CLIGS serves as a means to overcome a major limitation of cationic liposomes with a prolonged precorneal retention time, enhanced stability, and convenient administration due to the modified gelatinization temperature; this justifies their use as a carrier adjuvant for ocular delivery behaviors. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Quercetin-encapsulated magnetoliposomes: Fabrication,optimization, characterization,and antioxidant studies

Quercetin (QU) faces challenges in its therapeutic efficacy due to its hydrophobic nature and limited oral bioavailability. Using a Box–Behnken design (BBD) approach, we developed QU-loaded magnetoliposomes (QMLs) to address these limitations. By encapsulating QU within iron oxide nanoparticles (IONPs) and liposomes (LPs), we enhanced its hydrophilicity and improved its potential for drug delivery. Through systematic adjustments of phosal, polyvinyl alcohol, and magnetic/IONPs, we optimized the particle size, zeta potential, and iron content of the QMLs. The formulations underwent comprehensive structural characterization using techniques, such as Fourier transform infrared spectroscopy, X-Ray diffraction, differential scanning calorimetry–thermogravimetric analysis, and energy-dispersive X-ray analysis, whereas their morphology was examined through field emission scanning electron microscopy. Furthermore, we evaluated the in vitro drug release of the QMLs and antioxidant activity of QU, QU-loaded LPs, and QMLs using DPPH, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and H₂O₂ scavenging assays, enabling us to compare their antioxidant potential and the efficiency of QU encapsulation within the magneto LPs. Practical Applications: This research holds significant practical implications, particularly in targeted drug delivery using magnetic liposomes. The developed system shows promise in enhancing cancer therapy, providing localized treatment for inflammation-related conditions, delivering drugs to the brain to address neurological disorders, promoting wound healing, and incorporating quercetin into skincare products for its antioxidant and antiaging benefits.     

pH/redox/thermo-stimulative nanogels with enhanced thermosensitivity via incorporation of cationic and anionic components for anticancer drug delivery

To explore the potential biomedical applications of nanogels, it is a key factor to improve their thermosensitivity. In this paper, triple-responsive nanogels poly(N-isopropylacrylamide–N,N′-dimethylaminoethyl methacrylate–acrylic acid) (PNDA) were synthesized via in situ incorporating both cationic components and anionic components into a normal thermosensitive polymer matrix. The triple-monomer constructed PNDA nanogels displayed an enhanced thermosensitivity as compared with dual-monomer constructed PND nanogels. The PNDA nanogels presented higher encapsulation efficiency (～89%) and exhibited better pH/redox/thermo-responsivenesses in an anticancer drug delivery. In vitro biological study indicated that the PNDA nanogels have excellent biocompatibility and improved anticancer cytotoxicity to A549 cells after loading drug DOX.     

Functionalized bacterial cellulose nanowhiskers as long‐lasting drug nanocarrier for antibiotics and anticancer drugs

A nano drug carrier based on sustainable and biocompatible nanocellulose was developed for use in prolonged drug releases. The grafting of β‐cyclodextrin (βCD) on bacterial cellulose nanowhiskers (BCNC) using citric acid (CA) as a green linker was performed. This led to the formation of functionalized BCNC‐grafted‐βCD (BCNC‐g‐βCD). Broad‐spectrum antibiotic Ciprofloxacin (CIP) and anticancer drugs Doxorubicin (DOX) and Paclitaxel (PTX) were used as model drugs. These model drugs were conjugated to BCNC‐g‐βCD to form the drug‐nanocarrier systems (BCNC‐g‐βCD‐drug). The change in the nanowhiskers’ surface chemistry, morphology, and crystallinity was characterized by FTIR, solid‐state ¹³C NMR, scanning electron microscopy (SEM), atomic force microscopy (AFM), and x‐ray diffraction (XRD). The functionalized nanowhiskers showed a significant increase in the drug payloads, which ranged from 495 ±4–810 ±7 μg/mg, along with a radical improvement in the drug release profiles. For all of the developed drug‐conjugated nanocarriers, the initial burst releases were reduced effectively. The observed drug releases showed a sustained and controlled manner, with cumulative releases of 75–90 % over 5–5.5 days. Nevertheless, an improved drug release performance was observed in the acidic pH of 6.4 that mimicked extracellular tumor cells. In vitro drug release data were fitted zero‐order kinetic model with drug release constants (K₀) of 0.68, 0.74, and 0.79 μg drug/h (at pH 6.4 and 37 °C) for BCNC‐g‐βCD‐CIP, BCNC‐g‐βCD‐DOX, and BCNC‐g‐βCD‐PTX nanosystems, respectively. The observed higher payloads along with the slow releases of drugs from the developed nanocarrier suggests its promising potential for reducing the frequent daily dosing and minimizing systemic toxicity of loaded drugs.     

PMMA‐based microgels for controlled release of an anticancer drug

Methyl methacrylate (MMA), methoxy poly(ethylene glycol) monomaleate (MPEG), and acrylamidoglycolic acid (AGA) terpolymeric microgels (MGs) have been synthesized by free‐radical surfactant‐free emulsion polymerization. MPEG was synthesized from maleic anhydride and methoxy poly(ethylene glycol). The MGs were crosslinked with ethylene glycol dimethacrylate, and the chemical crosslinking was confirmed by Fourier transform infrared spectroscopy. 5‐Fluorouracil (5‐FU), a model anticancer drug, has been loaded into the MGs by in situ and adsorption methods. Empty as well as drug‐loaded MGs were then characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and X‐ray diffraction (XRD). DSC and XRD studies indicated a molecular level dispersion of the drug in PMMA MGs during in situ loading. TEM images showed the formation of spherical MGs. In vitro release of 5‐FU from the crosslinked poly(MMA‐co‐AGA‐co‐MPEG) MGs were investigated at both pH 7.4 and 1.2 buffer medium that controlled release of the drug up to ～ 18 h. Both the encapsulation efficiency and the release patterns were dependent on the amount of crosslinking agent and the amount of drug loaded. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Dual pH‐ and thermal‐responsive nanocomposite hydrogels for controllable delivery of hydrophobic drug baicalein

Hydrogels have been widely used as mild biomaterials due to their bio‐affinity, high drug loading capability and controllable release profiles. However, hydrogel‐based carriers are greatly limited for the delivery of hydrophobic payloads due to the lack of hydrophobic binding sites. Herein, nano‐liposome micelles were embedded in semi‐interpenetrating poly[(N‐isopropylacrylamide)‐co‐chitosan] (PNIPAAm‐co‐CS) and poly[(N‐isopropylacrylamide)‐co‐(sodium alginate)] (PNIPAAm‐co‐SA) hydrogels which were responsive to both temperature and pH, thereby establishing tunable nanocomposite hydrogel delivery systems. Nano‐micelles formed via the self‐assembly of phospholipid could serve as the link between hydrophobic drug and hydrophilic hydrogel due to their special amphiphilic structure. The results of transmission and scanning electron microscopies and infrared spectroscopy showed that the porous hydrogels were successfully fabricated and the liposomes encapsulated with baicalein could be well contained in the network. In addition, the experimental results of response release in vitro revealed that the smart hydrogels showed different degree of sensitiveness under different pH and temperature stimuli. The results of the study demonstrate that combining PNIPAAm‐co‐SA and PNIPAAm‐co‐CS hydrogels with liposomes encapsulated with hydrophobic drugs is a feasible method for hydrophobic drug delivery and have potential application prospects in the medical field. © 2018 Society of Chemical Industry     

Preparation of new dendrimer‐like star‐shaped amphiphilic poly(ethylene glycol)–poly(ϵ‐caprolactone) copolymers for biocompatible and high‐efficiency curcumin delivery

Novel amphiphilic star‐shaped terpolymers comprised of hydrophobic poly(?‐caprolactone), pH‐sensitive polyaminoester block and hydrophilic poly(ethylene glycol) (M_n = 1100, 2000 g mol^?1) were synthesized using symmetric pentaerythritol as the core initiator for ring‐opening polymerization (ROP) reaction of ?‐caprolactone functionalized with amino ester dendrimer structure at all chain ends. Subsequently, a second ROP reaction was performed by means of four‐arm star‐shaped poly(?‐caprolactone) macromer with eight ‐OH end groups as the macro‐initiator followed by the attachment of a poly(ethylene glycol) block at the end of each chain via a macromolecular coupling reaction. The molecular structures were verified using Fourier transform infrared and ¹H NMR spectroscopies and gel permeation chromatography. The terpolymers easily formed core–shell structural nanoparticles as micelles in aqueous solution which enhanced drug solubility. The hydrodynamic diameter of these agglomerates was found to be 91–104 nm, as measured using dynamic light scattering. The hydrophobic anticancer drug curcumin was loaded effectively into the polymeric micelles. The drug‐loaded nanoparticles were characterized for drug loading content, encapsulation efficiency, drug–polymer interaction and in vitro drug release profiles. Drug release studies showed an initial burst followed by a sustained release of the entrapped drug over a period of 7days at pH = 7.4 and 5.5. The release behaviours from the obtained drug‐loaded nanoparticles indicated that the rate of drug release could be effectively controlled by pH value. Altogether, these results demonstrate that the designed nanoparticles have great potential as hydrophobic drug delivery carriers for cancer therapy. © 2015 Society of Chemical Industry     

Synthesis of a novel polymer cholesterol‐poly(ethylene glycol) 2000‐glycyrrhetinic acid (chol‐PEG‐GA) and its application in brucine liposome

In this research, a novel polymer cholesterol‐poly(ethylene glycol) 2000‐glycyrrhetinic acid (Chol‐PEG‐GA) was synthesized with four steps of chemical modification and elucidated by FTIR and ¹H‐NMR spectra. To demonstrate the application of this Chol‐PEG‐GA in preparation of liposomes (CPGL), conventional liposome (CL) composed of PC and Chol was prepared and the effects of the quantity of Chol‐PEG‐GA on the physicochemical properties (entrapment efficiency, particle size, stability of storage, and so on) of CPGL were also evaluated. The ability of the sustained release and the liver targeting ability of CPGL were further studied in vivo in rats and mice. The results show that, the AUC and MRT of CPGL were increased 2.31 and 2.11 times when compared with CL, respectively. The CPGL delivered about seven times higher drug into liver as compared with CL. From the targeting parameters of CPGL and CL, we can also conclude that the CPGL is able to improve the liver targeting of brucine. All these results suggested that, the Chol‐PEG‐GA modified liposomes were potential as the sustained and liver targeting drug delivery. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis and application of methoxy poly(ethylene glycol)‐bile salts conjugates in physicochemical characterization and the pharmacokinetics of the liposomal bifendate in rats

Stealth liposomes have been broadly investigated as drug delivery or diagnostic agent. However, the materials that possess the ability of stealth, such as DSPE‐PEG and Chol‐PEG, are either costly or synthetic complex. In this research with different molecular weights (2000–6000 g/mol) of methoxy poly(ethylene glycol)(MePEG), a series of MePEG‐bile (MePB) conjugates were generated by an economical and simple method and confirmed by FTIR and ¹H‐NMR spectrum. The properties in aqueous solution were studied, including viscosity and surface activity, over a wide concentration range. To elucidate the application of MePB in liposomes (MePBL), conventional liposomes (CL) were prepared, and the influence of the grafting density and the chain length of MePB in liposomes were investigated. The ability of long circulation of MePBL was evaluated by intravenous injection administration in rats. Results indicated that all the liposomes prepared, with or without MePB composition, were similar in micrograph, and the contents of MePB in MePBL were more important than the chain length of MePB for a long circulation in vivo. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Temperature/pH/magnetic triple‐sensitive nanogel–hydrogel nanocomposite for release of anticancer drug

Hydrogels, nanogels and nanocomposites show increasing potential for application in drug delivery systems due to their good chemical and physical properties. Therefore, we were encouraged to combine them to produce a new compound with unique properties for a long‐term drug release system. In this regard, the design and application of a nanocomposite hydrogel containing entrapped nanogel for drug delivery are demonstrated. To this aim, we first prepared an iron oxide nanocomposite nanogel based on poly(N‐isopropylacrylamide)‐co‐((2‐dimethylaminoethyl) methacrylate) (PNIPAM‐co‐PDMA) grafted onto sodium alginate (NaAlg) as a biocompatible polymer and iron oxide nanoparticles (ION) as nanometric base (PND/ION‐NG). This was then added into a solution of PDMA grafted onto NaAlg. Through dropwise addition of mixed aqueous solution of iron salts into the prepared polymeric solution, a novel hydrogel nanocomposite with excellent pH, thermal and magnetic responsivity was fabricated. The synthesized samples were fully characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy with energy‐dispersive X‐ray analysis, vibrating sample magnetometry and atomic force microscopy. A mechanism for the formation of PNIPAM‐co‐PDMA/NaAlg‐ION nanogel–PDMA/NaAlg‐ION hydrogel and PND/ION nanogel is suggested. Swelling capacity was measured at various temperatures (25 to 45 °C), pH values (from 2 to 11) and magnetic field and under load (0.3 psi) and the dependence of swelling properties of the nanogel–hydrogel nanocomposite on these factors was well demonstrated. The release rate of doxorubicin hydrochloride (DOX) as an anticancer drug was studied at different pH values and temperatures in the presence and absence of a magnetic field. The results showed that these factors have a high impact on drug release from this nanocomposite. The result showed that DOX release could be sustained for up to 12.5 days from these nanocomposite hydrogels, significantly longer than that achievable using the constituent hydrogel or nanogel alone (<1 day). The results indicated that the nanogel–hydrogel nanocomposite can serve as a novel nanocarrier for anticancer drug delivery. © 2019 Society of Chemical Industry     

Pilocarpine‐loaded poly(DL‐lactic‐co‐glycolic acid) nanoparticles as potential candidates for controlled drug delivery with enhanced ocular pharmacological response

The poor corneal residence time of pilocarpine, an alkaloid extracted from the leaves of the Jaborandi plant, limits its ocular application. The aim of this study was to develop, characterize, and evaluate the potential of pilocarpine entrapped by poly(DL ‐lactic‐co‐glycolic acid) (PLGA) nanoparticle carriers for ocular drug delivery. Pilocarpine‐loaded nanoparticles were prepared with a double‐emulsion (water in oil in water) method and characterized with transmission electron microscopy and X‐ray diffraction analysis. The nanoparticles exhibited an average size of 82.7 nm with an encapsulation efficiency of 57%. Stability studies showed the absence of agglomeration and constancy in the amount of drug entrapped; this indicated the solidity of these particles for long‐term use. The in vitro release studies conducted in simulated tear fluid showed the sustained release of pilocarpine. In vivo evaluation of the nanoparticles was done in a rabbit model with a miosis assay and compared to an equal dose of commercially available eye drops of pilocarpine (Pilocar drops). The in vivo miosis studies showed that the duration of miotic response increased by 40% for the nanoparticles and produced an almost 68% increase in total miotic response when compared to the eye drops. In conclusion, this study clearly demonstrated the potential of pilocarpine‐loaded PLGA nanoparticles for multiplying the therapeutic effect of ophthalmic drug delivery with enhanced bioavailability and pharmacological response. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012