Drug Release Process Research Articles

The 2D platelet confinement effect on the membrane hole structure probed by electrochemical impedance spectroscopy

In this paper, ethyl cellulose (EC)/montmorillonite (MMT) composite membranes were prepared. As a potential candidate for drug delivery, the hole structures during acid treatment were characterized by XRD, SEM and electrochemical impedance spectroscopy (EIS). SEM pictures showed the formation of micrometer-size holes after adding MMT in the EC matrix. A new time constant appeared in the impedance spectrum of the composite membrane, implying structure variation by MMT. These rigid platelets would confine the relaxation of EC chain segments around MMT in the phase inversion process. During the acid treatment, EIS results indicated these micrometer-size holes would tend to shrink while the small holes in the EC matrix enlarged. The shrinkage of the micrometer-size holes could be attributed to the chain disentanglement due to the acid treatment. The above results suggest that it is easier to distinguish the hole variation by EIS, which is beneficial for analyzing the mechanism of the drug-releasing process.

EFFECT OF CELLULOSIC POLYMER ON PHYSICO MECHANICAL PROPERTIES OF SUPERPOROUS HYDROGEL OF AN ANTIHYPERTENSIVE DRUG AND DRUG RELEASE KINETICS FROM IT

Objective: Super porous hydrogels (SPHs), a novel drug delivery system can be developed to retain drugs in the gastric medium. The aim of the present investigation was to prepare superporous hydrogels (SPHs) of Atenolol to release the drug in sustained manner in the gastric environment and study the effect of two grades of hydroxyl methyl cellulose along with Carbopol 971p on the physico mechanical properties and drug release kinetics of the formulations.
 Methods: Superporous hydrogels of Atenolol were prepared with two grades of Hydroxy Propyl Methyl Cellulose (HPMC K100M and HPMC K15 M) along with Carbopol 971p the structural morphology of hydrogel was observed by Scanning Electron Microscopy. Study on Physico mechanical characteristics and drug release were done.
 Results: Scanning Electron microscopy studies of the formulations revealed the presence of large number of pores in different size ranges like 1 µm, 2 µm, 10 µm, confirming the formulations as superporous hydrogel. A correlation had been found between porosity, density and % swelling index. The drug release data from the formulations obeyed Higuchi and Korsmeyer-Peppas kinetics. Further, the data were fitted to the Kopcha model for confirming drug release by a combination of diffusion-controlled and chain relaxation–swelling mechanism.
 Conclusion: Among the six formulations, where HPMC K15 M and HPMC K100 M both were present, the gel became more hydrophobic and retarded the release of drug. From the drug release kinetics data, it can be concluded that the diffusion mechanism predominated the drug release process, leading to quasi diffusion and Fickian diffusion mechanism.

Degradable, thermo-, pH- and redox-sensitive hydrogel microcapsules for burst and sustained release of drugs.

Polymer microcapsules offer a possibility of storing increased amounts of drugs. Appropriate design and composition of the microcapsules allow tuning of the drug-release process. In this paper, we report on synthesis of hydrogel microcapsules sensitive to temperature and pH and degradable by glutathione and hydrogen peroxide. Microcapsules were based on thermo-responsive poly(N-isopropylacrylamide) and degradable cystine crosslinker, and were synthesized by applying precipitation polymerization. Such way of polymerization was appropriately modified to limit the crosslinking in the microcapsule center. This led to a possibility of washing out the pNIPA core at room temperature and the formation of a capsule. Microcapsules revealed rather high drug-loading capacity of ca. 17%. The degradation of the microcapsules by the reducing agent (GSH) and the oxidizing agent (H2O2) was confirmed by using the DLS, UV-Vis, SEM and TEM techniques. Depending on pH and concentration of the reducing/oxidizing agents a fast or slow degradation of the microcapsules and a burst or long-term release of doxorubicin (DOX) were observed. The DOX loaded microcapsules appeared to be cytotoxic against A2780 cancer cells similarly to DOX alone, while unloaded microcapsules did not inhibit proliferation of the cells.

Synthesis of Cucurbitacin Intercalated Hydrotalcite-like Compound Nanohybrids via Delamination-coassembling Method†

A nanohybrid of cucurbitacin( CA),a charge-neutral and poorly water-soluble drug,intercalated hydrotalcite-like compounds( HTlc) was synthesized via a delamination-coassembling method. CA molecules were initially incorporated into the micelles of sodium cholate( Ch),and the resulting negatively charged CAloaded micelles and the positively charged delaminated HTlc nanosheets were then coassembled together into the CA-Ch-HTlc nanohybrid. The so-obtained nanohybrid was characterized by small angle X-ray scattering,Fourier transform infrared,transmission and scanning electron microscopy,zeta potential and elemental analyses. The results showed that the loading of CA in the nanohybrid was 7. 06%,indicating that this route could be used to achieve the effective intercalation of charge-neutral and poorly water-soluble drugs into the HTlc gallery. Based on the sizes of Ch and CA,and the gallery heights of the nanohybrid,a possible orientation of Ch anions and CA molecules in the HTlc gallery was proposed. The Ch anions are arranged as a slightly tilted bilayer with their long axis approximately perpendicular to the brucite-like layer,and the CA molecules are encapsulated in the bilayer as a consequence of the hydrophobic interactions. The in vitro release of CA from the nanohybrid was examined,and the results showed that the nanohybrid had a good drug controlled release performance and its drug release process obeyed pseudo-second order kinetics model.

Design of l-Lysine-Based Organogelators and Their Applications in Drug Release Processes.

This work reports on the synthesis of three new l-lysine-based organogelators bis(N2-alkanoyl-N6-l-lysyl ethylester)oxalylamides, where alkanoyls are lauroyl, myristoyl, and palmitoyl. The gels of these gelators were prepared with high yields in eco-friendly solvents commonly used in cosmetics such as ethyl and isopropyl esters of lauric and myristic acids, liquid paraffin, 1-decanol, and 1,2-propanediol. Fourier transform infrared measurements revealed the involvement of intermolecular hydrogen bonds in the gelation. Scanning electron microscopy images of xerogels indicated different morphologic patterns with regard to the alkanoyl chain length and the solvent employed in their preparation. The gel formation was supported by rheological measurements. Three gels prepared in liquid paraffin were loaded with naproxen (Npx) with a quite high loading capacity (up to 166.6% as percentage of gelator) without gel disruption. The release of Npx from the gel matrix into the buffered solution at physiologic pH was evaluated using UV–vis spectroscopy. The results revealed that the release rate of Npx from the organogels significantly retarded with increasing organogelator concentration, whereas it enhanced with increasing Npx concentration. The rate was also found to be pH-dependent; the lower the pH, the lower the rate. Furthermore, molecular dynamic calculations performed on the octamer of myristoyl-bearing gelator (N2M/N6Lys) in 1,2-propanediol provided useful information regarding the structural properties of the gels, which may be of interest to interpret the structure of the gel matrix. Altogether, this work provided valuable outcomes, which may be relevant to the pharmaceutical industry. It may be suggested that l-lysine-based gels have potentials in the delivery of nonsteroidal anti-inflammatory drug molecules. Besides, the release of the drug can be fine-tuned by the correct choice of gelator–solvent combination.

Investigation of chloramphenicol release from PVA/CMC/HEA hydrogel using ion beam analysis, UV and FTIR techniques

PVA/CMC/HEA based cross-linked hydrogels were synthesized. These were utilized as matrix chloramphenicol drug releasing systems. Combination of different analytical techniques was applied to understand drug releasing process. Ion beam analysis (IBA) measurements, namely micro-PIXE analysis, were applied to gain information regarding spatial distribution of chloramphenicol within the system. Independent complement measurements utilizing UV and pore volume measurements were also employed to additionally characterize and verify the experimental findings obtained by IBA techniques. FTIR was utilized to both characterize and justify the releasing behavior of the crosslinked systems. Comprehensive literature comparison between different analytical methods has been reviewed.

Cancer cell membrane as gate keeper of mesoporous silica nanoparticles and photothermal-triggered membrane fusion to release the encapsulated anticancer drug

The cancer cell membrane (CCM) is widely used for nanomedicine encapsulation to improve their tumor-targeting ability. However, few researches are focused on drug release process and mechanism of these composite. Cell membrane fusion (two separate lipid membranes merge into a single continuous bilayer), one of the most fundamental processes in biology could be promoted by heating. Thus, in this manuscript, CCM was exploited as the gate keeper and tumor-targeting moiety of anticancer drug-loaded mesoporous silica nanoparticles (MSN). In addition, the drug release process and mechanism based on cell membrane fusion were studied. The loaded drugs included indocyanine green (ICG), a FDA-approved near-infrared photothermal agent for clinical applications, and doxorubicin (DOX), a chemotherapy drug. By coating CCM on drug-loaded MSN, the keeper could prevent unexpected drug leaking during the circulation and provide tumor targeting based on its specific recognition function. After arriving tumor tissue post-tail vein injection, the tumor position is irradiated by 808 nm light to trigger light–thermal conversion process of ICG to heat the composite (DOX-ICG@MSN@CCM) and promote cell membrane fusion between the encapsulated CCM and targeted tumor cell membrane. Such process can enhance the uptake efficacy of DOX-ICG@MSN@CCM to tumor cells. Furthermore, ICG could provide a synergistic photothermal therapy activity with DOX.

AIE Supramolecular Assembly with FRET Effect for Visualizing Drug Delivery.

Here, we constructed a nanostructured pH/redox dual-responsive supramolecular drug carrier with both aggregation-induced emission (AIE) and Forster resonance energy transfer (FRET) effects, which enabled selective drug release and monitoring drug delivery and release processes. Taking the hyperbranched polyamide amine (H-PAMAM) with intrinsic AIE effects as the core, poly(ethylene glycol) (PEG) was bridged on its periphery by dithiodipropionic acid. Then, through the host-guest interaction of PEG and α-cyclodextrin, the supramolecular nanoparticles with AIE effects were constructed to load the anticancer drug doxorubicin (DOX). The supramolecular assembly has sufficiently large DOX loading due to the abundant cavities formed by branched structures. The hyperbranched core H-PAMAM has strong fluorescence, and the dynamic track of drug carriers and the dynamic drug release process can be monitored by the AIE and FRET effects between H-PAMAM and DOX, respectively. Furthermore, the introduction of disulfide bonds and the pH sensitivity of H-PAMAM enable the achievement of rapid selective release of loaded DOX at the tumor while remaining stable under normal physiological conditions. In vitro cytotoxicity indicates that the drug-loaded supramolecular assembly has a good therapeutic effect on cancer. In addition, the H-PAMAM core is different from the traditional AIE functional group, which has no conjugated structure, such as a benzene ring, thereby providing better biocompatibility. This technology will have broad applications as a new drug delivery system.

Molecular interactions between PAMAM dendrimer and some medicines that suppress the growth of hepatitis virus (Adefovir, Entecavir, Telbivudine, Lamivudine, Tenofovir): a theoretical study

Viral hepatitis is a common viral infection, can be dangerous, involves the body and leads to inflammation and destruction of tissue and normal function of the liver. Viral hepatitis is a major cause of premature death in human beings. According to the World Health Organization, it was assumed that there are more than 385 and 170 million carriers of hepatitis B and C in the world, respectively, and more than a million deaths occur due to hepatitis each year. There are a few specific drugs to treat hepatitis. To overcome some of these problems, nanoparticle systems containing organic and inorganic compounds are used for pharmaceutical purpose. One of these nanostructures is dendrimer. Dendrimers are repetitively branched nanomolecules. In this study, a theoretical study of the structural probabilities of nanostructure complex formation between polyamidoamine dendrimers (PAMAM) and some drugs that suppress the growth of hepatitis virus (Adefovir, Entecavir, Telbivudine, Lamivudine, Tenofovir: 1–5) has been carried out. The possibility of drug release, drug delivery and drug separation by PAMAM has been investigated. MMFF94 method has been used to provide results and medical solutions. In all the drug–PAMAM complexes, the relative energy levels of the complex energy have been calculated by the RHF/PM6 method. Medicine delivery, release process of drugs and separation of drugs from the in vivo and in vitro real sample were the main enforceable results obtained from this theoretical study of medicines 1–5 & PAMAM. This model has predicted an imaginary method to separate the medicines from real samples and study the drug release process of the discussed complexes. The imaginary separation procedure that suppresses the growth of hepatitis virus–1–5 medicine mixture in in vitro samples is discussed. It is possible to collect compounds 1 and 2 by PAMAM and separate Adefovir, Telbivudine and Tenofovir (3–5) from the mixture of the sample of medicines 1–5.

Self-emulsifying drug delivery systems with atorvastatin adsorbed on solid carriers: formulation and in vitro drug release studies

Two novel self-emulsifying drug delivery systems (SEDDS) with atorvastatin calcium, an anti-hyperlipidemic drug, were obtained and adsorbed on different solid inorganic carriers. In order to determine the parameters affecting the drug release process, different physicochemical analyses were performed. Liquid SEDDS were investigated for water solubilization capacity, viscosity and surface tension. In the case of solid materials, differential scanning calorimetry and scanning electron microscopy were conducted in order to check the samples for the presence of drug crystals. The interactions between the components of the materials were analyzed with inverse gas chromatography and Flory-Huggins parameters were calculated. The drug release experiments performed for all investigated formulations revealed that after the initial quick release the drug concentration in the dissolution medium decreased slightly which might be related to the crystallization process. However, the level of the released active ingredient was maintained at 80% for most formulations. It was also shown that the results of drug dissolution studies were independent of the measured physicochemical parameters, even though some clear differences have been observed between the analyzed materials.

Molecular dynamics simulation of anticancer drug delivery from carbon nanotube using metal nanowires.

In this study, we have investigated delivery of cisplatin as the anticancer drug molecules in different carbon nanotubes (CNTs) in the gas phase using molecular dynamics simulation. We examined the shape and composition of the releasing agent by using the different nanowires and nanoclusters. We also investigated the doping effect on the drug delivery process using N-, Si, B-, and Fe-doped CNTs. Different thermodynamics, structural, and dynamical properties have been studied by using the pure and different doped CNTs in this study. Our results show that the doping of the CNT has significant effect on the rate of the drug releasing process regardless of the composition of the releasing agent. © 2019 Wiley Periodicals, Inc.

Increasing the anticancer activity of azidothymidine toward the breast cancer via rational design of magnetic drug carrier based on molecular imprinting technology

Cancer treatment based anticancer drugs face serious obstacles. To prevail these obstacles, an effective targeted drug carrier can be imperative. This study aimed to design rationally an imprinting strategy for the carrying of a model anticancer drug, Azidothymidine via molecular imprinting technology. Considering the identity and affinity of monomers and cross-linkers to AZT, this work succeeded to establish an exclusive procedure to significantly improve the process of imprinting the Azidothymidine. Imprinting process was carried out on the surface of vinyl-modified silica coated Fe3O4 nanoparticles toward the delivery of azidothymidine to targeted tissue by external magnetic field. The resultant carrier was characterized by FT-IR, XRD, VSM, FESEM, EDX, BET, TGA. The AZT loading process on the nanocarrier is followed with Freundlich adsorption isotherm (QMAX:170 mg/g) and pseudo-second order fast adsorption kinetic (5 min). The release process of AZT from nanocarrier was fitted with First-Order and Higuchi dynamic model. Eventually, the involvement of magnetic nanocarrier was investigated on apoptosis in MCF-7 (cancer cell line) and MCF-10 (normal cell line). The cytotoxicity percentage on MCF-7 cells for magnetic nanocarrier was about 49 times greater than the azidothymidine, but did not affect MCF-10 cells. The corresponding results appropriately disclosed that the cytotoxicity of proposed nanocarrier on MCF-7 cells is through the caspase3 activity. The drug loading and release process as well as in-vitro studies of magnetic carrier were compared with bare carrier. This study indicates that the proposed magnetic carrier can be used as a promising drug carrier toward the breast cancer treatment.

Engineering Sustainable Antimicrobial Release in Silica-Cellulose Membrane with CaCO3-Aided Processing for Wound Dressing Application.

The sustained release of antimicrobial therapeutics for wound dressing has become an attractive design strategy for prolonging the timespan of wound dressings and for reducing the risk of chronic wound infection. Recently, cellulose-based membrane has become a preferred option of wound dressings for the treatment of burn wounds and skin ulcers. In this work, novel cellulose membrane incorporated with mesoporous silica particles (SBA-15) was developed as an antimicrobial wound dressing with desirable sustained release functionality for targeting persistent bacterial pathogens. Attributed to a coated layer of calcium carbonate (CaCO3), SBA-15 particles were free from corrosion in alkaline condition during the preparation of cellulose-based composite membranes. SEM, TEM and BET results showed that the morphology, specific surface area, pore size and pore volume of pristine SBA-15 were preserved after the incorporation of CaCO3-coated SBA-15 into the cellulose matrix, while the mesoporous structure of SBA-15 was significantly disrupted without the use of CaCO3 coating. The resultant composite membranes containing 30 wt% SBA-15 (denoted as CM-Ca2-SBA(30%)) achieved 3.6 wt% of antimicrobial drug loading. Interestingly, CM-Ca2-SBA(30%) demonstrated the sustained release property of chloramphenicol for 270 h, driven by a two-stage drug release processes of SBA-15/cellulose. The water vapor permeability (WVTR) and swelling properties of composite membranes were shown to have complied with the primary requirements of wound dressing. Antibacterial assays revealed that strong antibacterial activities (144 h) of the composite membranes against Staphylococcus aureus and Eschericia coli were achieved. All results displayed that the strategy of coating silica with CaCO3 helps to obtain cellulose–silica composite membranes with desirable sustained release profiles and strong antibacterial activities. The antibacterial SBA-15/cellulose composite membranes show potential for the application of wound dressing.

Novel propyl karaya gum nanogels for bosentan: In vitro and in vivo drug delivery performance

The amphiphilic propyl Karaya gum (KG) with a degree of propyl group substitution of 3.24 was synthesized to design self-assembled nanogels as carriers for bosentan monohydrate, a poorly soluble antihypertensive drug. The drug was physically hosted into the hydrophobic core of the micellar nanogels by solvent evaporation method. TEM images revealed spherical shape and core-shell morphology of the nanogels. Depending upon polymer: drug weight ratio, the drug entrapment efficiency of >85% was attained. The carriers had hydrodynamic diameter in the range of 230–305 nm with narrow size distribution. The zeta potential of −23.0 to −24.9 mV and low critical association concentration (CAC) of 8.32 mg/l provided evidence that the colloidal nanogel system was physically stable. Thermodynamics of the propyl KG system in water favored spontaneous self-assembly of propyl KG. FTIR, thermal and x-ray analyses suggested that the drug was compatible in the hydrophobic confines of the nanogels. The micellar nanogels liberated their contents in simulated gastrointestinal condition in a pH-dependent manner over a period of 10 h. Peppas-Sahlin modeling of in vitro drug release data suggested that the polymer relaxation/swelling mechanism dominated the drug release process. Pre-clinical testing of the mucoadhesive nanogel formulations exhibited that the system could monitor the anti-hypertensive activity for a prolonged period. Overall, this propyl KG micellar nanogel system had a great potential and splendid outlook to serve as novel oral controlled release carriers for poorly soluble drugs with outstanding pharmacodynamics.

Manufacturing of pH sensitive PVA/PVP/MWCNT and PVA/PEG/MWCNT nanocomposites: an approach for significant drug release

The purpose of this paper is studying the effect of incorporation of Multiwall Carbon Nanotubes (MWCNT) into two different nanocomposites in poly vinyl alcohol (PVA)/polyvinylpyrrolidone (PVP), and PVA/Polyethylene glycol (PEG). MWCNT were synthesized by chemical vapor deposition (CVD) method using acetylene and Fe/Co/Al2O3 as carbon precursor and catalyst, respectively. Nitric acid and sulfuric acid were used for purification and functionalization of MWCNT. Afterward, highly pure and functionalized MWCNT (0, 0.02, and 0.05% w/w) were incorporated in PVA/PVP and PVA/PEG to synthesize PVA/PVP/MWCNT and PVA/PEG/MWCNT nanocomposites hydrogel membranes that cross-linked by freezing–thawing. PEG and PVP were selected in these nanocomposites as dispersion matrix for MWCNT as well as for increasing the elasticity of the nanocomposites membranes. The morphology of the hydrogels was characterized by SEM, FTIR, XRD, TGA, and the mechanical properties of the hydrogel membranes were investigated. The swelling behavior in different pH-buffer solutions was studied as well as studying weight loss percentage and swelling kinetic. The drug releasing process of the hydrogel membranes was investigated using salicylic acid as a model drug. It was found that MWCNT are dispersed well into the polymers and crystallinity, mechanical properties and thermal stability of the hydrogels contain MWCNT are better than that without MWCNT. Maximum degree of swelling was observed at pH 7 and swelling degree increases with increasing the ratio of MWCNT in the hydrogels from 0.02 to 0.05%. All hydrogel membranes followed non-Fickian mechanism and drug releasing were controlled by varying the pH and amount of MWCNT.

Injectable Schiff base polysaccharide hydrogels for intraocular drug loading and release.

A novel voriconazole (VCZ)-loaded injectable hydrogel was in situ synthetized via a Schiff base reaction between polyaldehyde dextran (PAD) and carboxymethyl chitosan (CMCTS) for intraocular drug loading and release. Water-insoluble VCZ, which is an effective agent in clinic treating fungal endophthalmitis, was loaded through the inclusion into the β-cyclodextrin (β-CD) cavity based on host-guest interaction on the linear poly β-CD chain, which was in situ twined in the cross-linked hydrogel structure. The gelation time, degradation, and drug release process were investigated by studying three kinds of hydrogels with different volume ratio of PAD to CMCTS resolving in phosphate buffered saline (PBS) solution (3:7, 6:7, 9:7), respectively. The property of VCZ-loaded injectable hydrogel should be adjusted through changing the cross-linked density of the hydrogel, the molecular weight or concentration of the linear poly β-CD to meet the treating requirement, and a multistage drug controlled-release mechanism was proposed. In conclusion, the VCZ-loaded in situ injectable hydrogel should be offered as a promising strategy for intraocular drug delivery in vitreous cavity for the treatment of fungal endophthalmitis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1909-1916, 2019.

Complex of chitosan pectin and clay as diclofenac carrier

The preparation of a new drug delivery system (DDS) based on the combination of two natural polymers chitosan (CS) and high-esterified pectin (HEP) and beidellite (Bd) was proposed. Diclofenac sodium was chosen as model drug and was loaded in the nanocomposite by means of intercalation solution technique. The samples were characterized by X-ray diffraction, Thermal analysis, Infrared spectroscopy and high resolution transmission electron microscopy coupled with energy dispersive X-Ray analysis. Drug loading capacity and encapsulation efficiency of the clay polymer nanocomposite was quantified. UV–Vis spectroscopy (276 nm) was used as the drug quantification technique throughout the whole study. In vitro drug release profile in simulated intestinal fluid was also evaluated. Results demonstrated the formation of diclofenac polymorph during the drug loading process, thus obtaining a new crystal form of the drug possessing different physico-chemical properties with respect to the diclofenac sodium salt form. Moreover, the in vitro release study showed that the bionanocomposite elaborated could form a network aiming for a modified release of diclofenac. Consequently, Na-Bd/CS/HEP nanocomposite proved to be a promising formulation to control anionic drug release process.

Kinetical Release Study of Copper Ferrite Nanoparticle Incorporated on PCL/Collagen Nanofiber for Naproxen Delivery

Nanofiber has become one of tissue engineering examples and has extensive application on medical field, particularly as a wound healing and wound dressing. In this research, nanofiber composite based on polycaprolactone and collagen was successfully obtained via electrospinning process and further developed as host of naproxen as anti-inflammatory agents. Addition of copper ferrite (CuFe2O4) nanoparticles on the nanocomposite becomes an advance part on this study to control of naproxen release. Several characterizations were furnished to prove the design composite nanofiber and its drug release analysis performed to find out the kinetic model and naproxen release mechanism from nanofibers. CuFe2O4 nanoparticles have potential to be used to control naproxen release in nanofiber that lead to decrease level of drug released, where mostly follow the Korsmeyer-Peppas model. The release of naproxen was certainly influenced by pH value, in which the drug was easier to release on base, instead of acid or neutral condition. Varied naproxen and nanoparticle compositions were prepared to reach optimum formulation of the release. This study provides fundamental data for the effect of magnetic nanoparticle on drug release process.

DPD studies on mixed micelles self-assembled from MPEG-PDEAEMA and MPEG-PCL for controlled doxorubicin release.

In order to better understand and improve the drug loading capacity and release behavior of the pH-responsive mixed micelles in well controlled pH environments, dissipative particle dynamics (DPD) simulations are employed. This is performed by studying the co-micellization behavior of these materials produced from the two specific diblock polymers, poly(ethylene glycol) methyl ether-b-poly(N, N diethylamino ethyl methacrylate) (MPEG-PDEAEMA) and poly(ethylene glycol) methyl ether-b-polycaprolactone (MPEG-PCL) for doxorubicin (DOX) delivery. With the use of appropriate interaction parameters, the formation mechanism of (drug-loaded) mixed micelles, particle sizes, morphology, and composition are investigated. Simulation results show that compared with pure MPEG-PDEAEMA or MPEG-PCL, the mixed MPEG-PDEAEMA and MPEG-PCL system can combine to form multifunctional mixed micelles with larger particle sizes that lead to improved stability, higher drug loading capacity and better-controlled drug release performance. Simulations of the drug release process using the mixed micelles show that, when the environment is acidic, the tertiary amine group of PDEAEMA and DOX3 lead to rapid diffusion and release of the DOX in the aqueous solution. It is found that the presence of MPEG-PCL has a great influence in avoiding the fast release of the drug inside the core of micelles. Therefore, this study offers a deeper understanding of the mechanism on the co-micellization behaviors, the pH-responsive and drug controlled release behaviors of mixed micelles.

Facile preparation of pyrenemethyl ester-based nanovalve on mesoporous silica coated upconversion nanoparticle for NIR light-triggered drug release with potential monitoring capability

A novel light-responsive nanovalve is facilely prepared on mesoporous silica (mSiO2) coated upconversion nanoparticles (UCNP) through modification of photo-cleavagable pyrenemethyl ester (Py) molecules on its surface. These Py molecules can associate with β-cyclodextrin (β-CD) molecules as gatekeepers to block the mSiO2 pore channels and entrap the loaded drugs. Upon NIR light irradiation, NIR light is upconverted to ultraviolet (UV) and visible (Vis) light by UCNP, and the modified Py molecules are cleaved by the upconverted UV light leading to the detachment of β-CD gatekeepers to trigger drug release. For the fabrication of a monitoring system, β-CD is covalently conjugated with the fluorescein isothiocyanate (FITC) as drug release indicator (FITC-β-CD). The luminescence resonance energy transfer (LRET) from UCNP to Py/FITC-β-CD before drug release results in the quenching of Vis emission of UCNP while the detachment of Py/FITC-β-CD nanovalves after drug release diminishes the LRET between UCNP and FITC-β-CD which recovers the luminescence of UCNP, the change in luminescence provides a potential capability for one to quantitatively monitor the drug release process. in vitro study shows a remarkable killing ability on HeLa cancer cell of this system.