Real-time Drug Release Research Articles

Bimodal real-time monitoring and dual responsive drug release based on Janus mesoporous silica-Au nanoparticles

loaded solid lipid nanoparticles (Ber-SLN) composed of cremophor EL and glyceryl behenate were prepared by high pressure homogenization technique. Anti-diabetic effects of Ber-SLN relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-SLN were 154.3 ± 4.1 nm and −19.7 ± 0.46 mV, respectively. Ber-SLN (50 mg/kg) treatment via oral gavage 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-SLN decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as SLN is a promising approach for treating type 2 diabetes.

Bioinspired fluorescent dipeptide nanoparticles for targeted cancer cell imaging and real-time monitoring of drug release.

Peptide nanostructures are biodegradable and are suitable for many biomedical applications. However, to be useful imaging probes, the limited intrinsic optical properties of peptides must be overcome. Here we show the formation of tryptophan-phenylalanine dipeptide nanoparticles (DNPs) that can shift the peptide's intrinsic fluorescent signal from the ultraviolet to the visible range. The visible emission signal allows the DNPs to act as imaging and sensing probes. The peptide design is inspired by the red shift seen in the yellow fluorescent protein that results from π-π stacking and by the enhanced fluorescence intensity seen in the green fluorescent protein mutant, BFPms1, which results from the structure rigidification by Zn(II). We show that DNPs are photostable, biocompatible and have a narrow emission bandwidth and visible fluorescence properties. DNPs functionalized with the MUC1 aptamer and doxorubicin can target cancer cells and can be used to image and monitor drug release in real time.

Fabrication of Graphene and AuNP Core Polyaniline Shell Nanocomposites as Multifunctional Theranostic Platforms for SERS Real-time Monitoring and Chemo-photothermal Therapy.

In this work, novel theranostic platforms based on graphene oxide and AuNP core polyaniline shell (GO-Au@PANI) nanocomposites are fabricated for simultaneous SERS imaging and chemo-photothermal therapy. PANI, a new NIR photothermal therapy agent with strong NIR absorption, outstanding stability and low cytotoxicity is decorated on AuNPs by one-pot oxidative polymerization, then the Au@PANI core-shell nanoparticles are attached to the graphene oxide (GO) sheet via π-π stacking and electrostatic interaction. The obtained GO-Au@PANI nanohybirds exhibit excellent NIR photothermal transduction efficiency and ultrahigh drug-loading capacity. The nanocomposites can also serve as novel NIR SERS probes utilizing the intense SERS signals of PANI. Rapid SERS imaging of cancer cells is achieved using this ultrasensitive nanoprobe. GO-Au@PANI also reveals good capability of drug delivery with the DOX-loading efficiency of 189.2% and sensitive NIR/pH-responsive DOX release. The intracellular real-time drug release dynamics from the nanocomposites is monitored by SERS-fluorescence dual mode imaging. Finally, chemo-photothermal ablation of cancer cells is carried out in vitro and in vivo using GO-Au@PANI as high-performance chemo-photothermal therapeutic nanoagent. The theranostic applications of GO-Au@PANI endow it with great potential for personalized and precise cancer medicine.

Two-photon sensitized hollow Gd2O3:Eu(3+) nanocomposites for real-time dual-mode imaging and monitoring of anticancer drug release.

New two-photon sensitized multifunctional nanocomposites were designed for dual-mode imaging and real-time drug release monitoring by photoluminescence (PL) and magnetic resonance imaging (MRI). By drug loading based on coordination effect, PL signals of Eu(3+) and MRI signals of Gd(3+) can be stabilized and enhanced, respectively, which then display excellent linear decreases on drug release.

Real-Time Drug Release Analysis of Enzyme and pH Responsive Polysaccharide Nanovesicles.

The accurate estimation of drug release kinetics of polymeric vehicles is an indispensable prerequisite for the developments of successful drug carriers for cancer therapy. The present investigation reports the development of time-resolved fluorescence spectroscopic approach for the real-time release kinetics of fluorophore loaded polysaccharide vesicles that are potential vectors in cancer treatment. The polysaccharide vesicles were custom designed with appropriate enzyme and pH responsiveness and loaded with water-soluble biocompatible fluorophore Rhodamine B (Rh-B). The semipermeable membrane dialysis method along with steady state absorbance spectroscopic technique was found to be inaccurate for the estimation of drug release. Time correlated single photon counting (TCSPC) technique was found to exhibit significant difference in excited state decay profiles and fluorescent lifetime of Rh-B in the free and polymer bound states. This enabled the establishment of real-time drug release protocols by TCSPC method for polysaccharide vesicles that are responsible to pH and enzyme with respect to intracellular compartments. Real-time analysis predicted the release kinetics 20-25% higher accuracy when compared to the dialysis method under in vitro conditions. Moreover, the ability of enzyme to cleave the polysaccharide vesicles was further validated by docking studies. The positioning of the molecules in active site of enzyme and the binding energy data were generated using AUTODOCK program to study the rupture of polysaccharide vesicles. This new TCSPC technique could be very useful for studying the drug release pattern of synthetic polymer vesicles loaded with Rh-B fluorophore.

A Review of In Vitro Drug Release Test Methods for Nano-Sized Dosage Forms

This review summarizes the methods used to study real-time (37°C) drug release from nanoparticulate drug delivery systems and establish an IVIVC. Since no compendial standards exist, drug release is currently assessed using a variety of methods including sample and separate (SS), continuous flow (CF), dialysis membrane (DM) methods, and a combination thereof, as well as novel techniques like voltametry and turbidimetry. This review describes the principle of each method along with their advantages and disadvantages, including challenges with set-up and sampling. The SS method allows direct measurement of drug release with simple set-up requirements, but sampling is cumbersome. With the CF method, sampling is straightforward but the set-up is time consuming. Set-up as well as sampling is easier with the DM, but it may not be suitable for drugs that bind to the membrane. Novel methods offer the possibility of real-time drug release measurement but may be restricted to certain types of drugs. Of these methods, Level A IVIVCs have been obtained with dialysis, alone or in combination with the sample and separate technique. Future efforts should focus on developing mathematical models that describe drug release mechanisms as well as facilitate formulation development of nano-sized dosage forms.

SERS-fluorescence monitored drug release of a redox-responsive nanocarrier based on graphene oxide in tumor cells.

A redox-responsive drug carrier based on nanoscale graphene oxide (NGO) loaded with Ag nanoparticles, whose intracellular release behavior can be investigated by SERS-fluorescence combined spectroscopy, is presented. In this demonstrated drug carrier, to make the carrier integrated with the redox responsive property, we utilized disulfide linkages to load drug molecules to the surfaces of NGO directly, which can be cleaved by glutathione (GSH). Covalent drug loading and GSH-responsive release strategy can reduce the influence of the surface diffusion barriers introduced by multifunctionalization. Interestingly, the intracellular real-time drug release dynamics can be monitored by the combined SERS-fluorescence signals of the drugs, while the distribution of the drug carrier can simultaneously be tracked by the intrinsic SERS signals of NGO in the whole process. Our results show that upon the internalization of doxorubicin (DOX)-loaded nanocarriers into living cells, DOX was efficiently released under a GSH regulated reducing environment. Because tumor cells generally exhibit a higher concentration of GSH than normal ones, this drug carrier should have potential in the field of tumor therapy.

A pH-responsive prodrug for real-time drug release monitoring and targeted cancer therapy.

A novel cancer targeting and pH-responsive prodrug was successfully designed and synthesized. This M-prodrug was demonstrated to have real-time drug release monitoring capability based on the concept of contact-mediated quenching between doxorubicin and a coumarin derivative.

Evaluation of psoralen ethosomes for topical delivery in rats by using in vivo microdialysis

This study aimed to improve skin permeation and deposition of psoralen by using ethosomes and to investigate real-time drug release in the deep skin in rats. We used a uniform design method to evaluate the effects of different ethosome formulations on entrapment efficiency and drug skin deposition. Using in vitro and in vivo methods, we investigated skin penetration and release from psoralen-loaded ethosomes in comparison with an ethanol tincture. In in vitro studies, the use of ethosomes was associated with a 6.56-fold greater skin deposition of psoralen than that achieved with the use of the tincture. In vivo skin microdialysis showed that the peak concentration and area under the curve of psoralen from ethosomes were approximately 3.37 and 2.34 times higher, respectively, than those of psoralen from the tincture. Moreover, it revealed that the percutaneous permeability of ethosomes was greater when applied to the abdomen than when applied to the chest or scapulas. Enhanced permeation and skin deposition of psoralen delivered by ethosomes may help reduce toxicity and improve the efficacy of long-term psoralen treatment.

Carbon nanomaterials as drug carriers: Real time drug release investigation

The use of carbon nanomaterials in biomedical applications and the cytotoxicity of these materials have been areas of great interest during the last decade. In vitro drug load and release, as well as in vivo animal tests, have been carried out using carbon nanomaterials. However, no comparison studies on the drug load and the release of different carbon nanomaterials have been reported. Here, we report on a real time investigation of the drug release of carbon black (CB) nanoparticles, carbon nanotubes (CNTs) and graphene oxide (GO), using rhodamine B (RB) as a model of drug. The binding of RB to the nanomaterials were characterized by FTIR and UV–vis. The mass loading capacities of these nanomaterials were also studied, showing that GO had the highest capacity. The real time drug release experiment indicated different accumulative release modes of these nanomaterials at different pH values, due to their different binding modes with RB, which is also discussed as being the reason for the mechanism differences. Moreover, the comparison of the drug release capacity of CNT–RB and f-CNT–RB (functionalized-CNT–RB) indicated an influence of hydrogen bonds in both drug loading and release, as the hydrogen bonds increased the loading capacity of the carbon nanotube after acid treatment and changed the drug release mechanism at pH 7.4. Thus, here we identified the drug release modes of the different carbon nanomaterials. The results of the influence of functional groups and hydrogen bonds point also out a potential way of controlling the drug release behavior of carbon nanomaterials by surface modification.

Real-time monitoring of anticancer drug release in vitro and in vivo on titania nanoparticles triggered by external glutathione

The anticancer drug doxorubicin (DOX) appeared to adsorb efficiently on TiO2 nanoparticles (NPs) as evidenced by visible absorption and diffuse reflectance infrared spectroscopy data. The adsorbed drugs were found released in a controlled way by external glutathione (GSH). Fluorescence of DOX appeared to be quenched substantially by TiO2 NPs. The fabrication and release of DOX on TiO2 NPs were checked by monitoring the fluorescence. We could monitor real-time drug release in the live cell using fluorescence imaging techniques. By these methods, we were able to monitor up to a nanomolar amount of DOX release in vitro from TiO2 NPs triggered by external GSH. In vivo fluorescence images of DOX were obtained from the subcutaneous site in living mice after GSH treatment. On the basis of label-free fluorescence quenching measurements, a real-time release of DOX on TiO2 NPs can be monitored in vitro and in vivo after an external trigger of GSH.

A microfluidic chip platform with electrochemical carbon nanotube electrodes for pre-clinical evaluation of antibiotics nanocapsules

This paper presents a microfluidic chip platform with electrochemical carbon nanotube electrodes for preclinical evaluation of antibiotics nanocapsules. Currently, there has been an increasing interest in the development of nanocapsules for drug delivery applications for localized treatments of diseases. So far, the methods to detect antibiotics are liquid chromatography (LC), high performance liquid chromatography (HPLC), mass spectroscopy (MS). These conventional instruments are bulky, expensive, not ease of access, and talented operator required. In order to help the development of nanocapsules and understand drug release profile before planning the clinical experiments, it is important to set up a biosensing platform which could monitor and evaluate the real-time drug release profile of nanocapsules with high sensitivity and long-term measurement ability. In this work, a microfluidic chip platform with electrochemical carbon nanotube electrodes has been developed and characterized for rapid detection of antibiotics teicoplanin nanocapsules. Multi-walled carbon nanotubes are used to modify the gold electrode surfaces to enhance the performance of the electrochemical biosensors. Experimental results show that the limit of detection of the developed platform using carbon nanotubes electrodes is 0.1 μg/ml with a linear range from 1 μg/ml to 10 μg/ml. The sensitivity of the developed system is 0.023 mA ml/μg at 37 °C. The drug release profile of teicoplanin nanocapsules in PBS shows that the antibiotics nanocapsules significantly increased the release of drug on the 4th day, measuring 0.4858 μg/(ml hr). The release of drug from the antibiotics nanocapsules reached 34.98 μg/ml on the 7th day. The results showed a similar trend compared with the measurement result using the HPLC instrument. Compared with the traditional HPLC measurements, the electrochemical sensing platform we developed measures results with increased flexibility in controlling experimental factors for long-term preclinical measurement of nanocapsules in real time and at low cost.

Real-time monitoring of drug release

A new prodrug system, assembled using a distinctive coumarin linker, was demonstrated to report real-time activation and drug release in vitro.

In Situ Fiber-Optic Dissolution Assisted by a Mathematical Separation Model of Dynamic Three-Wavelength K-Ratio Spectrophotometry

The aim of this study was to monitor the drug release of ibuprofen sustained-release capsules in real time in situ. A mathematical separation model of dynamic three-wavelength K-ratio spectrophotometry was established to eliminate the interference of gelatin capsule shells when drug release was monitored by a fiber-optic drug dissolution in situ test system. A control experiment with high performance liquid chromatography was performed simultaneously. Within 7 h, real-time drug release profiles were obtained. The average drug release rates were 19.79%, 37.34%, 63.13%, and 88.41% by the fiber-optic drug dissolution in situ test system at the respective time points of 1 h, 2 h, 4 h, and 7 h. There were no significant differences between the in situ and control methods. Drug release of ibuprofen sustained-release capsules can be monitored by the fiber-optic drug dissolution in situ test system assisted by the mathematical separation model of dynamic three-wavelength K-ratio spectrophotometry. Information about the entire dissolution process can be produced by the real-time release profile.

Monitoring Ambroxol Hydrochloride Sustained-Release Tablets Release by Fiber-Optic Drug Dissolution In Situ Test System

The purpose of this research was to monitor in situ the drug release of ambroxol hydrochloride sustained-release tablets using a fiber-optic dissolution test system. A control experiment with a UV-vis spectrophotometer was performed simultaneously. Within 4 h, a real-time drug release profile was obtained. The average drug release at 60 min, 120 min, and 240 min was 23.1%, 52.2%, and 87.6%, respectively, using the fiber-optic in situ system. There were no significant differences between the two methods. The drug release of sustained-release tablets can be monitored by a fiber-optic drug dissolution in situ test system. Information about the whole dissolution process can be produced by the real-time dissolution profile.

The Study of a Remote-Controlled Gastrointestinal Drug Delivery and Sampling System

A micromachined capsule based on microelectromechanical systems (MEMS) technology is introduced in this paper. It is an effective tool for diagnosing and treating gastrointestinal diseases. The microcapsule can carry out real-time drug release and the gastrointestinal fluid sampling in the gastrointestinal tract. According to the structural and metabolic characters of the gastrointestinal tract, the configuration of the microcapsule was designed as a cylinder. This nondigestible oral device can smoothly pass through the gastrointestinal tract for drug delivery and liquid sampling. The working mechanism of the capsule was the mechanic movement mode of a piston, which was regulated through a MEMS calorific element. The action of drug delivery and gastrointestinal fluid sampling in the gastrointestinal tract was performed wirelessly. The remote control device can be connected with a computer through a serial port (RS-232), and it can be used in telemedicine applications. Some experimental research has been carried out to validate the design. The experimental results indicated that the microcapsule can achieve drug delivery and liquid sample reliably.

Real-Time Drug Release Imaging From Nanocomposite Drug and Polymer Coatings

The ElectroNanospray process (Nanocopoeia, Inc) transforms drugs and polymers into many nanoscale material states including powders, liquids, encapsulated particles, and coatings. This allows application of polymers and drugs to the surface of medical devices such as coronary stents in a single-stage process. A model drug delivery system consisting of a polymer matrix (arborescent polyisobutylene-polystyrene, or arbIBS) and either dexamethasone or sirolimus was studied by various characterization techniques. Modification of ElectroNanospray process parameters resulted in surface coatings with rich morphologies that are revealed by SEM, Atomic Force Microscopy (AFM) and Confocal Raman Microscopy were employed to monitor the drug release process in situ, through which the mechanism of the drug-eluting process may be proposed. A Confocal Raman microscope fitted with underwater objective was used to image arbIBS∕drug films incubated in phosphate-buffered saline over 12h and at various film depths. Drug migrated from more concentrated areas into the surrounding polymer and toward the surface, beginning as early as 5min after placing the sample in buffer and continuing throughout the 12h period. High drug levels remained in the more concentrated areas at the end of incubation, suggesting the potential for prolonged release. SEM and AFM images taken from samples post incubation showed the appearance of nanoscale pores ∼100nm in diameter in areas corresponding in size and distribution to the Confocal Raman planar image areas of increased drug concentration. Confocal Raman microscopy offers a powerful new technique for demonstrating real-time drug release from therapeutic medical device coatings.

Methods to Assess in Vitro Drug Release from Injectable Polymeric Particulate Systems

This review provides a compilation of the methods used to study real-time (37 degrees C) drug release from parenteral microparticulate drug delivery systems administered via the subcutaneous or intramuscular route. Current methods fall into three broad categories, viz., sample and separate, flow-through cell, and dialysis techniques. The principle of the specific method employed along with the advantages and disadvantages are described. With the "sample and separate" technique, drug-loaded microparticles are introduced into a vessel, and release is monitored over time by analysis of supernatant or drug remaining in the microspheres. In the "flow-through cell" technique, media is continuously circulated through a column containing drug-loaded microparticles followed by analysis of the eluent. The "dialysis" method achieves a physical separation of the drug-loaded microparticles from the release media by use of a membrane, which allows for sampling without interference of the microspheres. With all these methods, the setup and sampling techniques seem to influence in vitro release; the results are discussed in detail, and criteria to aid in selection of a method are stated. Attempts to establish in vitro-in vivo correlation for these injectable dosage forms are also discussed. It would be prudent to have an in vitro test method for microparticles that satisfies compendial and regulatory requirements, is user friendly, robust, and reproducible, and can be used for quality-control purposes at real-time and elevated temperatures.