Controlled Drug Release Properties Research Articles

A combination of experiment and molecular simulation studies on a new metal-organic framework showing pH-triggered drug release

A new Co(II)-based complex { [Co2(L)(4,4'-Bipy)2] · CH3CN} n (I) (H4L = 5,5'-(biphenyl-4,4'- diyl-bis(methylene))bis(oxy)diisophthalic acid, 4,4'-Bipy = 4,4'-bipyridine) has been synthesized and structurally characterized. Single-crystal X-ray analysis (CIF file CCDC no. 1406388) reveals that compound I has 3D pcu topology. The incorporation of the drug 5-fluorouracil (5-FU) into the desolvated I was around 15.0 wt % of dehydrated I. Complex I also shows a pH-triggered controlled drug release property. In addition, we used semiempirical AM1 method to investigate the adsorption of 5-FU to I at the molecular level.

Synthesis of sandwich-like molybdenum sulfide/mesoporous organosilica nanosheets for photo-thermal conversion and stimuli-responsive drug release

Sandwich-like molybdenum sulfide/mesoporous organosilica nanosheets (denoted as MoS2@MOS) have been prepared for the first time via direct growth of ethane-bridged mesostructured organosilica on MoS2 nanosheets by using cetyltrimethylammonium bromide (CTAB) as structure directing agent. The obtained MoS2@MOS nanosheets possess well-defined sandwich-like structure, high surface area (∼920cm2/g), uniform pore size (∼4.2nm), large pore volume (∼1.41cm3g−1). In vitro cytotoxicity assessments demonstrate that the MoS2@MOS nanosheets have excellent biocompatibility. Owing to the encapsulation of the MoS2, the obtained MoS2@MOS nanosheets have photo-thermal conversion capability and photo-thermally controlled drug release property. These properties make the MoS2@MOS nanosheets promising for biomedical applications.

Responsive Prodrug Self-Assembled Vesicles for Targeted Chemotherapy in Combination with Intracellular Imaging.

Targeted drug delivery systems having controlled drug release property with an inherent fluorescence reporter have drawn a lot of attention in nanomedicine. However, only very few prodrugs can be directly used to construct such delivery systems. Herein, we report that an amphiphilic chlorambucil-based prodrug consisting of a fluorescence reporter and a d-mannose targeting ligand could directly self-assemble into glutathione-responsive nanovesicles for selective cancer therapy and intracellular imaging. These nanovesicles could be dissociated to release the chlorambucil drug with obviously red-shifted fluorescence when internalized by d-mannose receptor-overexpressed MCF-7 cancer cells. In addition, the nanovesicles displayed better selectivity and higher therapy efficiency than free chlorambucil drug.

Production and Investigation of Controlled Drug Release Properties of Tamoxifen Loaded Alginate-Gum Arabic Microbeads

The entrapment of tamoxifen onto alginate-gum arabic beads and the production of controlled drug release was investigated in this study. The polymeric system that would provide the controlled release of tamoxifen was formed using alginate and gum arabic. In the first phase of the study, the optimization of the alginate-gum arabic beads production was conducted; then the study continued with drug entrapment experiments. Tamoxifen entrapment yield was found to be approximately 90% of initial tamoxifen concentration. In vitro drug release experiments were performed in simulated gastric juice and intestinal fluid where the tamoxifen release was 20% and 53% of the initial drug present, respectively. As a result of this study, it is expected that a valuable contribution to the field of controlled drug release system production is realized.

Tailoring the mucoadhesive and sustained release characteristics of mesalamine loaded formulations for local treatment of distal forms of ulcerative colitis

Direct delivery of sustained therapeutic levels of mesalamine (MS) via rectal systems to manage distal forms of ulcerative colitis was studied. The High molecular weight hydroxypropyl methylcellulose (HPMC K4M) polymer was combined with hydrophilic surfactants to control polymer hydration process allowing optimization of the mucoadhesive and controlled drug release properties for the rectal systems. Physical mixtures and granules of MS and HPMC K4M were prepared and in vitro characterized using scanning electron microscope, differential scanning calorimetry and X-ray diffraction techniques. Rectal formulations were prepared utilizing MS-HPMC K4M mixtures in different polyethylene glycol (PEG) combination bases. The developed rectal formulations were investigated for physical, mucoadhesion, in-vitro drug release and swelling characteristics. Results revealed acceptable physical characteristics of the prepared formulations with good content uniformity and minimum weight variation. Sustained release patterns of MS form HPMC K4M based formulations were observed. Formulations prepared using high proportions of the polymer or PEG 400 showed higher extent of mucoadhesion, swelling and greatly extended drug release time. Efficacy of an optimized formulation was assessed using the acetic acid induced colitis model in rats and compared to a reference polymer-free formulation of the drug. Clinical evaluation included bleeding from rectum, consistency of animal stool and colon/body weight ratio. Furthermore, histopathological analysis was carried out to evaluate the degree of inflammation and mucosal damage. Overall results showed a significant enhancement in the clinical pictures and colon histopathology of animals treated by the sustained release mucoadhesive formulation compared to the reference polymer free formulation and the non-treated colitis group.

Electrophoretically prepared hybrid materials for biopolymer hydrogel and layered ceramic nanoparticles.

BackgroundIn order to obtain biomaterials with controllable physicochemical properties, hybrid biomaterials composed of biocompatible biopolymers and ceramic nanoparticles have attracted interests. In this study, we prepared biopolymer/ceramic hybrids consisting of various natural biopolymers and layered double hydroxide (LDH) ceramic nanoparticles via an electrophoretic method. We studied the structures and controlled-release properties of these materials.Results and discussionX-ray diffraction (XRD) patterns and X-ray absorption spectra (XAS) showed that LDH nanoparticles were formed in a biopolymer hydrogel through electrophoretic reaction. Scanning electron microscopic (SEM) images showed that the ceramic nanoparticles were homogeneously distributed throughout the hydrogel matrix. An antioxidant agent (i.e., ferulic acid) was loaded onto agarose/LDH and gelatin/LDH hybrids, and the time-dependent release of ferulic acid was investigated via high-performance liquid chromatography (HPLC) for kinetic model fitting.ConclusionsBiopolymer/LDH hybrid materials that were prepared by electrophoretic method created a homogeneous composite of two components and possessed controllable drug release properties according to the type of biopolymer.

Bioactive apatite incorporated alginate microspheres with sustained drug-delivery for bone regeneration application

The strontium-substituted hydroxyapatite microspheres (SrHA) incorporated alginate composite microspheres (SrHA/Alginate) were prepared via adding SrHA/alginate suspension dropwise into calcium chloride solution, in which the gel beads were formed by means of crosslinking reaction. The structure, morphology and in vitro bioactivity of the composite microspheres were studied by using XRD, SEM and EDS methods. The biological behaviors were characterized and analyzed through inductively coupled plasma optical emission spectroscopy (ICP-OES), CCK-8, confocal laser microscope and ALP activity evaluations. The experimental results indicated that the synthetic SrHA/Alginate showed similar morphology to the well-known alginate microspheres (Alginate) and both of them possessed a great in vitro bioactivity. Compared with the control Alginate, the SrHA/Alginate enhanced MC3T3-E1 cell proliferation and ALP activity by releasing osteoinductive and osteogenic Sr ions. Furthermore, vancomycin was used as a model drug to investigate the drug release behaviors of the SrHA/Alginate, Alginate and SrHA. The results suggested that the SrHA/Alginate had a highest drug-loading efficiency and best controlled drug release properties. Additionally, the SrHA/Alginate was demonstrated to be pH-sensitive as well. The increase of the pH value in phosphate buffer solution (PBS) accelerated the vancomycin release. Accordingly, the multifunctional SrHA/Alginate can be applied in the field of bioactive drug carriers and bone filling materials.

A porous metal-organic framework with a unique hendecahedron-shaped cage: structure and controlled drug release.

A porous MOF constructed from a [Cu2(COO)4] secondary building unit, H3L (H3L = [1,1';3',1'']terphenyl-4,5',4''-tricarboxylic acid), and pyrazine ligands features a unique hendecahedron cage-like cavity with good stability and a high BET surface area of 3235 m(2) g(-1), showing good controlled drug release property of ibuprofen over those of anethole and guaiacol.

Fabrication of ampicillin/starch/polymer composite nanofibers with controlled drug release properties by electrospinning

Synthetic ampicillin (AM)/starch (ST)/polymer composite nanofibers were fabricated during the electrospinning process, and it was found that the nanofibers had efficient and controlled drug release properties. AM, an antibacterial drug, was successfully encapsulated inside the ST-based composite nanofibers. The addition of biocompatible polymers, polyvinyl alcohol and polyethylene oxide, could efficiently improve the electrospinnability of ST aqueous solutions. The results of the density functional theory (DFT) calculation indicate that hydrogen bond interactions exist between AM and ST. Through the in vitro drug release studies, it was found that the AM release properties of the ST-based composite nanofibers could be controlled through manipulating drug loading, the ratio of ST to polymers, the species of polymers, and the weight of tablet. Synthetic ampicillin/starch/polymer composite nanofibers were fabricated during the electrospinning process, and it was found that the nanofibers had efficient and controlled drug release properties. The release of ampicillin from the starch-based composite nanofibers could be efficiently controlled through manipulating the ratio of starch to polymers, drug loading, species of polymers, and weight of tablets. Additionally, DFT calculation was used to investigate the interaction between ampicillin and starch.

Synthesis, luminescent and drug-release properties of SiO2@Y2O3:Eu hollow mesoporous microspheres

SiO2@Y2O3:Eu hollow mesoporous microspheres were prepared by coating luminescent Y2O3:Eu3+ particles onto uniform silica spheres using melamine formaldehyde microspheres as sacrificial templates. Various approaches including X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared, thermogravimetric and differential thermal analysis, photoluminescence spectroscopy and N2 adsorption/desorption were used to characterize the samples. The results indicate that Y2O3:Eu3+ particles have been coated onto the hollow silica spheres with 300 nm thickness shell, and the composite microspheres exhibit mesoporous characteristics and have spherical morphology. Upon ultraviolet excitation, the composite shows the characteristic 5D0–7F1–4 red emission lines of Eu3+ even after loading of the model drug. In addition, drug release tests suggest that the composite has a controlled drug release property with ibuprofen as the model drug.

Potential antibacterial activity of triazine dendrimer: Synthesis and controllable drug release properties

A novel sustained release delivery system of ciprofloxacin was developed. The system consists of a viscosity enhancer plus a penetration enhancer to overcome penetration barriers and loss due to wash-out and thus achieve the desired ciprofloxacin ocular absorption. A macromolecule of piperazine core 1,3,5-triazine dendrimer with eight molecules of ciprofloxacin drug as a surface moiety has been synthesized in five steps. Antibacterial activities of this compound have been investigated for Gram-positive and Gram-negative bacteria like Staphylococcus aureus (mtcc 737), Bacillus subtilis (mtcc 2063), Escherichia coli (mtcc-443), Pseudomonas aeruginosa (mtcc 741) and Proteus mirabilis (mtcc425). It was observed that the influence of hydrophobic and hydrophilic balance per repeat unit of these dendrimer has profound effects for antibacterial activities. The MIC value of the compound very lower at 100μg/mL−1 when compared with standard ciprofloxacin at 500μg/mL−1. The compound (10) exhibits five times higher activity against tested organisms when compared with ciprofloxacin as standard. The structures of the dendrimers were determined by means of MALDI-TOF MS, NMR and IR studies. The in vitro release of ciprofloxacin from obtained dendrimer was investigated.

Magnetic microcapsules with inner asymmetric structure: Controlled preparation, mechanism, and application to drug release

Magnetic microcapsules with inner asymmetric structure are prepared by miniemulsion polymerization of styrene in presence of oleic acid-modified Fe3O4 as magnetic nanoparticles and n-heptane (HP) as core. The resultant microcapsules with novel structure exhibit magnetic anisotropy and cavity anisotropy. The formation mechanism of the microcapsule is illustrated in detail. The obtained results showed that the polymerization process is associated with phase-separation between polystyrene, oleic acid (OA) and HP. Based on this formation mechanism, a kind of highly asymmetric magnetic microcapsules are prepared, which is further verified the presented phase-separation mechanism. Meanwhile, four kinds of magnetic microcapsules with inner asymmetric structure, which show different shell thickness and cavity volume, are prepared for application to carrying and releasing drugs. The results reveal that the microcapsules exhibit excellent controlled drug release property and the release speed can be controlled by adjusting the thickness of the thinner-side capsule-wall. Drug loading and drug release of inner asymmetric magnetic microcapsules were from the thinner side of capsule-wall. This kind of novel microcapsule shows potential application value in unilateral or contact point controlled and concentrated release.

Silk fibroin-based nanoparticles for drug delivery.

Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By adjusting the particle size, the chemical structure and properties, the modified or recombinant SF-based nanoparticles can be designed to improve the therapeutic efficiency of drugs encapsulated into these nanoparticles. Therefore, they can be used to deliver small molecule drugs (e.g., anti-cancer drugs), protein and growth factor drugs, gene drugs, etc. This paper reviews recent progress on SF-based nanoparticles, including chemical structure, properties, and preparation methods. In addition, the applications of SF-based nanoparticles as carriers for therapeutic drugs are also reviewed.

Shape-memory bioresorbable terpolymer composite with antirestenotic drug

Shape-memory polymers (SMPs) that combine shape-memory, biodegradability, and controlled drug release properties are very promising for medical and pharmaceutical application. Moreover, incorporation of antirestenotic drug into SMP biodegrad- able stent seems to be an interesting solution because of possibility to combine the mechanical support that provides stent and also drug elution. The aim of our study was to analyze the effect of incorporation of sirolimus into poly(L-lactide-co-glycolide-co-trimethy- lene carbonate) on physicochemical and mechanical properties, degradation, and shape-memory effect of the terpolymer. For this purpose, sirolimus was incorporated into the terpolymer by injection molding method. It has been demonstrated that drug-free ter- polymer after injection molding characterized insignificant changes in terpolymer composition. Degradation of materials during proc- essing was not observed. Incorporation of drug molecules did not change shape-memory properties of terpolymer. 1 H- and 13 C-NMR spectra of poly(lactide-co-glycolide-co-trimethylene carbonate) confirmed that changes during degradation were similar for terpolymer and terpolymer with sirolimus. Sustained and regular release of sirolimus was observed. The developed material presents potential for biomedical and pharmaceutical applications. V C 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41902.

Amphiphilic block copolymer terminated with pyrene group: from switchable CO2-temperature dual responses to tunable fluorescence

Py-PCL-b-P(NIPAM-co-DMAEMA) micelles can present switchable CO2-temperature dual responses and tunable fluorescence properties.

Hierarchical construction of a mechanically stable peptide-graphene oxide hybrid hydrogel for drug delivery and pulsatile triggered release in vivo.

The design of hydrogels with controllable drug-release properties remains challenging. Here we report a hydrogel made of hierarchical graphene oxide sheets and peptide assemblies for on-demand drug release. The hydrogel possesses high drug-sustainability and the release of drugs can be precisely and remotely controlled through external stimuli.

Gompertz modeling을 이용한 약물유출 예측시스템의 최적화

Gompertz modeling은 고령화 사회에 접어들기 시작하며 노령인구 예측에 성공적인 결과를 보여줌으로써 최근 많은 주목을 받고 있다. 또한 항암 치료제의 독성으로 인해 발생할 수 있는 부작용을 미연에 방지하고자 보다 효과적인 치료제의 사용에 관한 의료 생체분야에서 활발한 개발이 시도되어 왔으나 전임상 및 임상실험으로의 응용이 가능한 모델링은 극히 제한적이며, 모델링의 검증을 위한 생체실험의 분석 시스템의 최적화가 힘들다는 한계가 있다. 본 논문에서는 Gompertz modeling을 응용하여 새로운 겸형적혈구의 약물유출 예측시스템을 개발하고, 여기된 광증감제의 겸형적혈구 부착을 통해 효과적인 약물유출 제어방법을 ex-vivo 실험을 통해 검증하여 최적화된 예측 시스템의 결과를 비교 분석 할 수 있었다. 따라서 이와 같이 최적화된 Gompertz modeling을 이용한 새로운 약물전달 시스템이 항암치료에 반영된다면 부작용에 기인한 환자들의 신체적 고통과 치료를 위한 경제적 부담을 경감시키는 효과를 유도하며, 나아가 항암 치료제의 정확한 전달률을 증가시켜 보다 효과적인 항암치료를 기대할 수 있다. A Gompertz modeling, sigmoid in shape, is a widely used application for social science, natural science, engineering, and medical research to allow confident approximation and accurate analysis and has been applied to estimate an elderly population on aging of population. Due to the high toxicity of currently available drug delivery vehicles, various efforts have been made to reduce side-effects in clinical fields, but its application to preclinical and clinical studies is limited and there are some difficulties to optimize the parameters of Gompertz modeling applicable to preclinical studies. Therefore, in this study, we demonstrated the ability of sickle red blood cells loaded by hypotonic dialysis then photosensitized and light-activated ex vivo for controlled release and simultaneously optimized Gompertz function to evaluate controlled drug release properties of photosensitized sickle red blood cells to reduce pain-related treatments in cancer patients.

Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

Multifunctional SiO2@Gd2O3:Yb/Tm hollow capsules: controllable synthesis and drug release properties.

A series of hollow and luminescent capsules have been fabricated by covering luminescent Gd2O3:Yb/Tm nanoparticles on the surface of uniform hollow mesoporous silica capsules (HMSCs), which were obtained from an etching process using Fe3O4 as hard templates. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), up-conversion (UC) fluorescence spectra, and N2 adsorption-desorption were used to characterize these samples. It is found that the as-prepared products have mesoporous pores, large specific surface, and high dispersity. In particular, the size, shape, surface area, and interior space of the composites can be finely tuned by adjusting the size and morphology of the magnetic cores. Under 980 nm near-infrared (NIR) laser irradiation, the composites show characteristic blue UC emissions of Tm(3+) even after carrying doxorubicin hydrochloride (DOX). The drug-release test reveals that the capsules showed an apparent sustained release character and released in a pH-sensitive manner. Interestingly, the UC luminescence intensity of the drug-carrying system increases with the released DOX, realizing the possibility to track or monitor the released drug by the change of UC fluorescence simultaneously, which should be highly promising in anticancer drug delivery and targeted cancer therapy.

High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol.