Synthesis of the Core-Shell Structure Materials as the Controlled-Release Drug Carrier

We have developed a controlled-release drug carrier. Smartly controlled-release polymer nanoparticles were firstly synthesized through RAFT polymerization as the controlled-release core. The structural and particle properties of polymer nanoparticles were characterized by nuclear magnetic resonance spectroscopy (1H-NMR), scanning electron microscope (SEM) and X-ray spectroscopy (EDX). Mesoporous materials were selected as the shell materials to encapsulate the smart core as the stable shell. The mesoporous shell was characterized by transmission electron microscopy (TEM) and scanning electron microscope (SEM). All the results showed that a well-defined core-shell structure with mesoporous structure was obtained, and this controllable delivery system will have the great potential in nanomedicine.

Preparation and Drug-Release Property of Polycaprolactone (PCL)/Polyglycolic Acid (PGA) Composite Masterbatch with Drug of Tea Polyphenols (TPs)

In order to effectively control the drug-release rate of medical textiles,biodegradable polycaprolactone(PCL) and polyglycolic acid(PGA) were blended at various mass ratios to prepare composite masterbatches for medical textiles.The surface morphology and the chemical structure of the masterbatches were analyzed.The crystallization,mass losses,strengths and drug-release rates of the composite masterbatches at different PCL/PGA mass ratios were explored.The results show that the degradation rate of the PGA carrier is obvious higher than that of the PCL carrier,and PCL,PGA and the tea polyphenol(TP) drug just physically mix without chemical reaction.During the degradation,the strength of the composite masterbatches gradually decreases.In addition,the drug-release rates of composite masterbatches at different mass ratios are different,and the more the PGA in the composite masterbatches,the faster the drug release of the composite masterbatches.The drug-release rate of the composite masterbatches can be controlled by adjusting the contents of PCL and PGA.

Anorectal Pharmacodynamics and In Vitro Drug Release of Clerodendrum bungei Steud.Extract Gel

[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition),and to study its anorectal pharmacodynamics and drug release in vitro.[Methods]Carbomer 940,propylene glycol and absolute ethyl alcohol were selected as the main factors,and the preparation technology of C.bungei Steud.extract gel was optimized by orthogonal test.The mouse model of ulcerative hemorrhoids was established with glacial acetic acid(HAC)and compared with Ma Yinglong musk hemorrhoids ointment.The recovery of trauma was compared between the two groups.At the same time,porcine small intestine was used as semi-permeable membrane to make diffusion cell to simulate anal environment,and the drug release in vitro was studied.[Results]The C.bungei Steud.extract gel was smooth in appearance and good in stability.It could effectively treat anal ulcer in mice and release quickly in vitro.[Conclusions]The formula is reasonable,and the effect of animal experiment is remarkable,which can provide a new treatment plan for ulcerative hemorrhoids.

A Simplified Expression for a Diffusion-Dissolution Con-trolled Release of Drug from Matrix in TDDS

Chandrasekran-paul (1982) made an equation of drug release from matrix system as follows:In this paper a simplified expression has been deduced from it within ordinary range of experimental time and with appropriate values of K. The cumulative amount of drug release may vary in directproportion to the square root of time with an intercept,that is,The release behaviour of both nifedipine patch and propranolol patch has fit the expression with good correlation coefficient.The re0lease data of hydrocortisone creams (Shah,1989)also can be described by the same expression.Compared with Higuchi’s equation,the presence of the intercept,A〃,may be relative to drug dissolution characteristics

Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release

This study aimed to prepare poly(D, L-lactic-co-glycolic acid) microspheres(PLGA-Ms)by a modified solid-in-oil-in-water(S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatideencapsulated lecithin nanoparticles(Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles(Ex-NPs) via the alcohol injection method,followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water(W/O/W) technique(Ex-PLGA-Ms), Ex-NPs-PLGAMs showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable cytotoxicity.In pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve(AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy.

Influence of Sorbitan Monooleate on Morphology and Drug Release Behavior of Emulsion Electrospinning Polycaprolactone Nanofibers

Ultrafine polycaprolactone(PCL)fibers containing watersoluble drug tetracycline hydrochloride(Tet)were prepared by emulsion electrospinning.Sorbitan monooleate(Span80)was added as an essential additive to form stable water/oil emulsions and fabricate fibers with core-sheath structure.Different concentrations of Span80(0-40 g/L)were used to investigate the stability of emulsion and size of dispersed droplets.The scanning electron microscope(SEM)images indicated that the morphology of the fibers with Span80 were beaded-free with diameters of 200-400 nm,and Span80 enhanced the spinnability of electrospinning solution.The laser scanning confocal microscope(LSCM)images indicated that Tet was well encapsulated into the core region of the PCL fibers.The transmission electron microscope(TEM)image showed the formation of core-sheath structure.The loading efficiency(LE)and entrapment efficiency(EE)of Tet were calculated and release profiles in artificial saliva buffer solution(pH=6.8)were also analyzed.The results revealed that LE and EE of fibers with Span80decreased with the increase of its concentration.Fibers with coresheath structure had a longer effective release lifetime than without Span80.The increase of Span80 resulted in higher hydrophilicity of fibers and faster release rate of Tet.

Hollow MnO_2/GNPs serving as a multiresponsive nanocarrier for controlled drug release

In this work,hollow manganese dioxide/gold nanoparticle(MnO2/GNPs)hybrid drug nanocarriers were prepared by coupling the gold nanoparticles(GNPs)with hollow structure manganese dioxide(MnO2).Among them,GNPs have been used as near-infrared(NIR)-responsive element for photothermal effect under NIR laser irradiation.The glutathione(GSH)-responsive and p H-responsive performances of drug release were derived from hollow MnO2.Particularly,Doxorubicin hydrochloride(DOX)can be loaded into hollow MnO2/GNPs with the drug loading efficiency up to 82.0%.Moreover,the photothermal effect and GSH-/pH-responsive properties of hollow MnO2/GNPs were investigated.The hollow MnO2/GNPs possessed satisfactory drug release efficiency(ca.87.4%of loaded drug released in 12 h)and have high photothermal conversion efficiency,multiresponsive properties,and degradability.Finally,the kinetics of drug release was discussed in detail.Thus,our finding highlights that the multiresponsive nanocarriers are of great potential in the field of drug controlled release.

Synthesis and Drug Release Properties of Thermosensitive Poly(N-vinylacetamide-co-vinylacetate) Hydrogels

Thermosensitive poly[N-vinylacetamide-co-vinylacetate][P（NVA-co-VAc）] hydrogels were prepared via free radical copolymerization from hydrophilic NVA and hydrophobic VAc in the presence of butylenes-bis （N-vinylacetamide）（Bis-NVA） as crosslinker. Scanning electron microscopy（SEM） images reveal that the as-prepared hydrogels were of three-dimensional network with irregular cave structure. The prepared hydrogels with more NVA in the feed swelled faster and the swelling ratio of the hydrogels gradually decreased with temperature increasing from 10 °C to 60 °C. The dynamic swelling studies indicate that the swelling process of the hydrogels was controlled by diffusion of water molecules considered as Fickian-controlled case. The adsorption amount of model drug, sodium salicylate（SS） was higher in the hydrogels containing more NVA units, whose corresponding release could reach equilibrium in about 6 h.

Fabrication and Drug Release Property of Silk Fibroin-Based Weft-Knitted Stents

This paper was to develop a weft-knitted stent coated by a drng-loaded electro-spun fibrous membrane and then investigate its morphology, mechan/cal properties and in vitro drug release property. This work was started by weft-knitting of an inner layer of such stent using polydioxanone （PDO） and silkf＇dment. Subsequently, 5-fluorouracil （5-FU） and curcnmin（CUR） loaded silk fibroin （SF） membranes were coated on the surface of the weft- knitted stent using electro-spinning technique to endow the drug delivery funct/on of the stent. The results show that the radial compression strength and c/renmferentlal expanding strength can reach above （9.1±0.4） cN/cm2 and （205.0± 0.2） cN/mm, respectively. The drug releasing behaviors can be sustained for 400 h. It is concluded that the stents have potential application as anintestinal stent in the future.

A MODEL FOR THE RELEASE BEHAVIOR OF DRUGS FROM HYDROGEL NANOPARTICLE

A model to correlate and predict the release behavior of drugs from hydrogel nanoparticles is presented in this paper. The nanoparticle is considered as a combination of a shell of an elastic semipermeable membrane and a core of a fluid phase （After swelling equilibrium）. The fluid core consists of network building materials and other components that are able to partition in hydrogel nanoparticle phase and surrounding coexisting liquid phase, and is enveloped by the membrane shell. The excess Gibbs energies of the hydrogel nanoparticle phase and the surrounding coexisting fluid phase are expressed e.g. using UNIQUAC equation with ＂free-volume＂ contribution for non-ionic solution and VERS-model for ionic one. The elastic properties of polymer network could be described, for example, by the ＂phanWm network＂ theory.

Milk-derived exosomes as a promising vehicle for oral delivery of hydrophilic biomacromolecule drugs

Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.

Development of NAMI-A-loaded PLGA-mPEG Nanoparticles:Physicochemical Characterization, in vitro Drug Release and in vivo Antitumor Efficacy

NAMI-A[imidazolium trans-tetrachloro(dimethylsulfoxide)imidazoleruthenium(Ⅲ)] shows extraordinary activities against metastatic tumors. However, the hydrolysis of NAMI-A to produce dimethyl sulfoxide(DMSO) could reduce anti-metastatic activity. To enhance the circulation time and the anti-metastatic effect of NAMI-A, NAMI-A-loaded nanoparticles were prepared by the double emulsion method and characterized by scanning electron microscopy for surface morphology, laser light scattering for size and zeta potential for surface charges. Controlled release of NAMI-A was observed in a sustained manner. Compared with free NAMI-A, NAMI-A-loaded nanoparticles exhibited superior antitumor effect by delaying tumor growth in T739 mice. PLGA-mPEG nanoparticles are promising for further studies as drug delivery carriers.

The Drug-carrier Interactions, Release Behaviors and Cell Responses of Hydroxyapaptite Containing Several Chinese Medicines

The present work shows drug-carrier interactions, release behaviors and cell responses of hydroxyapatite （HA） containing salvianolic acid B （Sal B）, astragalus polysaecharide （APS）, and naringin. X-ray diffraction （XRD） showed that the crystallinity and crystal size of HA decreased significantly when Sal B was added （p〈0.05）. Transmission electron microscope （TEM） confirmed that the nano-acicular crystals of HA containing Sal B were the most fine among all specimens. It was conjectured that Sal B preferentially adsorbed on the positively charged surface of HA crystals to inhibit their growth. In vitro release of HA containing Chinese medicines followed the first-order equation. The drug-carrier affinity between HA and Sal B might have prolonged the release of Sal B. The proliferation and differentiation of osteoblasts were promoted by Chinese medicines containing HA in the time and dosage dependent manner. The osteoblasts displayed a polygonal morphology with cell-cell junctions in all cases. It is suggested that the contained Chinese medicines would promote the activities of the osteoblasts.

Chemical Modification of EVA for DrugRelease Application

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Microwave-assisted Polymerization of ε-Caprolactone with Maleic Acid as Initiator and Drug Release Behavior of Ibuprofen-Poly(ε-caprolactone) System

Poly(e-caprolactone) (PCL) with weight-average molar mass over 10000 g/mol was synthesized by microwave-assisted ring-opening polymerization of e-caprolactone (e-CL) with maleic acid (MA) as initiator (2.45 GHz, 360 W, 85 min). Ibuprofen-PCL controlled release system was prepared directly by the ROP of e-CL in its mixture with ibuprofen. The release of ibuprofen from the system was sustained and steady.

Regulation of drug release performance using mixed doxorubicin-doxorubicin dimer nanoparticles as a pH-triggered drug self-delivery system

A mixed drug self-delivery system(DSDS)with high drug content(>50%)was developed to regulate pHtriggered drug release,based on two doxorubicin(DOX)-DOX dimmers:D-DOX_(ADH) and D-DOX_(car) conjugated with acid-labile dynamic covalent bonds(hydrazone and carbamate,respectively)and stabilized with PEGylated D-DOX_(ADH)(D-DOX_(ADH)-PEG).Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them,pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS.Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios.The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates.The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slowrelease mixed DSDS nanoparticles.

POLYCAPROLACTONE-POLY (ETHYLENE GLYCOL) BLOCK COPOLYMER Ⅲ DRUG RELEASE BEHAVIOR

The drug release behavior of degradable polymer--polycaprolactone-poly (ethyleneglycol)block copolymer(PCE) in vitro was investigated by using 5-Fluoro-uracil (5-Fu) asa model drug under a condition of pH 7. 4 at 37C. It is found that the release rate of 5-Fufrom PCE increased with increasing polyether content of the copolymer. The results showthat the increasing polyether content of the copolymer caused increasing hydrophilicity anddecreasing crystallinity of the PCE copolymer. Thus, the drug release behavior and thedegradable property of the PCE can be controlled by adjusting the composition of thecopolymer.

Novel Gelatin-Adriamycin Sustained Drug Release System for Intravesical Therapy of Bladder Cancer

To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo , its efficacy in inhibiting BIU 87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU 87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer..

Swelling and Drug Release Characteristics of Poly （methacrylic acid-co-poloxamer） hydrogels

Poly (methacrylic acid-co-poloxamer) hydrogel networks were synthesized byfree-radical solution polymerization, and the dynamic swelling and in vitro release properties ofmodel drugs, dextromethorphan hydrobromide (DMP) and vitamin B_(12) (VB_(12)) were studied. Thesegels exhibited pH-dependant swelling and sustained drug release properties, and the water uptakerate and drug release rate in neutral or basic media were higher than that in acidic media. Theresults showed that the water uptake followed non-Fickian or zero order process in neutral or basicmedia, and the release of model drugs from hydrogels of appropriate composition was of zero orderkinetics over a period of several hours.

Preparation and Drug-release Behavior of β-TCP Ceramics Drug Carrier in vitro

β-TCP ceramics drug carrier was first prepared and characterized. SEM showed that β-TCP carrier was in porous amorphous structure with diameters around 10 μm. The physical properties including apparent porosity, volume-weight, tensile strength and the permeability were measured and the results indicated those properties fit the clinical usage of β-TCP drug carrier. Furthermore, drug release experiment in vitro showed that the carrier could prolong drug release in simulated body fluid which provides basis for the clinical use of β-TCP ceramics as drug carrier.