Release Of Water-soluble Drugs Research Articles

PH-responsive nanofiber membranes for superior controlled release of poorly water-soluble drug and its release mechanism study

Antibiotics delivery using dressings is an effective manner to treat chronic infected wounds, but it still faces the challenge of uncontrolled drug release. To address this issue, we developed pH-responsive electrospun nanofibers for controlled release of poorly water-soluble antibiotics. Specifically, the drug-loaded electrospun nanofibers were fabricated via coaxial electrospinning technique, with polycaprolactone (PCL) and drug acting as the core and pH-responsive acrylic copolymer Eudragit L100–55 serving as the sheath layer. Under alkaline conditions, all drugs release rapidly due to the dissolution of Eudragit L100–55, and first-order model well fits the release behavior. In contrast, the sheath layer swells under acidic conditions, causing poorly water-soluble drugs to be firmly trapped. Moreover, the drug-loaded nanofibers display completely different antibacterial activities due to distinct drug release behaviors under alkaline or acidic conditions. The current pH-responsive nanofibers shows superior controllability of poorly water-soluble drug release, revealing great prospects for treating chronic infected wounds.

Kinematic Behavior of an Untethered, Small-Scale Hydrogel-Based Soft Robot in Response to Magneto-Thermal Stimuli.

Fruit fly larvae, which exist widely in nature, achieve peristaltic motion via the contraction and elongation of their bodies and the asymmetric friction generated by the front and rear parts of their bodies when they are in contact with the ground. Herein, we report the development of an untethered, magnetic, temperature-sensitive hydrogel-based soft robot that mimics the asymmetric micro-patterns of fruit-fly-larvae gastropods and utilizes cyclic deformation to achieve directional peristaltic locomotion. Due to Néel relaxation losses of nanomagnetic Fe3O4 particles, the hydrogel-based soft robot is capable of converting changes in external alternating magnetic stimuli into contracting and expanding deformation responses which can be remotely controlled via a high-frequency alternating magnetic field (AMF) to realize periodic actuation. Furthermore, the Fe3O4 particles included in the hydrogel-based soft robot cause it to follow a gradient magnetic field in confined liquid environments and can be coupled with AMFs for the targeted release of water-soluble drugs or targeted magnetic hyperthermia therapy (MHT). We believe that such a controlled motion can enable highly targeted drug delivery, as well as vascular disease detection and thrombus removal tasks, without the use of invasive procedures.

Biocomposite for Prolonged Release of Water-Soluble Drugs.

This study aimed to develop a prolonged-release system based on palygorskite and chitosan, which are natural ingredients widely available, affordable, and accessible. The chosen model drug was ethambutol (ETB), a tuberculostatic drug with high aqueous solubility and hygroscopicity, which is incompatible with other drugs used in tuberculosis therapy. The composites loaded with ETB were obtained using different proportions of palygorskite and chitosan through the spray drying technique. The main physicochemical properties of the microparticles were determined using XRD, FTIR, thermal analysis, and SEM. Additionally, the release profile and biocompatibility of the microparticles were evaluated. As a result, the chitosan-palygorskite composites loaded with the model drug appeared as spherical microparticles. The drug underwent amorphization within the microparticles, with an encapsulation efficiency greater than 84%. Furthermore, the microparticles exhibited prolonged release, particularly after the addition of palygorskite. They demonstrated biocompatibility in an in vitro model, and their release profile was influenced by the proportion of inputs in the formulation. Therefore, incorporating ETB into this system offers improved stability for the administered product in the initial tuberculosis pharmacotherapy dose, minimizing its contact with other tuberculostatic agents in the treatment, as well as reducing its hygroscopicity.

The Effect of Drug Heterogeneous Distributions within Core-Sheath Nanostructures on Its Sustained Release Profiles.

The sustained release of a water-soluble drug is always a key and important issue in pharmaceutics. In this study, using cellulose acetate (CA) as a biomacromolecular matrix, core-sheath nanofibers were developed for providing a sustained release of a model drug—metformin hydrochloride (MET). The core–sheath nanofibers were fabricated using modified tri-axial electrospinning, in which a detachable homemade spinneret was explored. A process—nanostructure–performance relationship was demonstrated through a series of characterizations. The prepared nanofibers F2 could release 95% of the loaded MET through a time period of 23.4 h and had no initial burst effect. The successful sustained release performances of MET can be attributed to the following factors: (1) the reasonable application of insoluble CA as the filament-forming carrier, which determined that the drug was released through a diffusion manner; (2) the core–sheath nanostructure provided the possibility of both encapsulating the drug completely and realizing the heterogeneous distributions of MET in the nanofibers with a higher drug load core than the sheath; (3) the thickness of the sheath sections were able to be exploited for further manipulating a better drug extended release performance. The mechanisms for manipulating the drug sustained release behaviors are proposed. The present proof-of-concept protocols can pave a new way to develop many novel biomolecule-based nanostructures for extending the release of water-soluble drugs.

Evaluating Release Kinetics from Alginate Beads Coated with Polyelectrolyte Layers for Sustained Drug Delivery.

Current approaches in stem cell-based bone tissue engineering require a release of bioactive compounds over up to 2 weeks. This study presents a polyelectrolyte-layered system featuring sustained release of water-soluble drugs with decreased burst release. The bioactive compounds adenosine 5'-triphosphate (ATP), suramin, and A740003 (a less water-soluble purinergic receptor ligand) were incorporated into alginate hydrogel beads subsequently layered with different polyelectrolytes (chitosan, poly(allyl amine), alginate, or lignosulfonate). Drug release into aqueous medium was monitored over 14 days and evaluated using Korsmeyer-Peppas, Peppas-Sahlin, Weibull models, and a Langmuir-like "Two-Stage" model. Release kinetics strongly depended on both the drug and the polyelectrolyte system. For ATP, five alternating layers of poly(allyl amine) and alginate proved to be most effective in sustaining the release. Release of suramin could be prolonged best with lignosulfonate as polyanion. A740003 showed prolonged release even without layering. Applying polyelectrolyte layers significantly slowed down the burst release. Release curves could be best described with the Langmuir-like model.

Zero-Order Controlled Release of Water-Soluble Drugs Using a Marker Pen Platform.

Zero-order drug release that releases drugs at a constant rate is beneficial to prolong the therapeutic effect and avoid the side effects of drugs. However, due to the weak interaction between the drug and the carrier, it is particularly challenging to achieve zero-order release of water-soluble drugs. Inspired by the marker pen, which stores the water-based ink in the sponge core and releases a constant amount of ink from the tip for writing, we explore the marker pen as a drug delivery platform to achieve zero-order release of water-soluble drugs. Through the capillary interaction between the material and water, the pen core can absorb the aqueous drug solution to encapsulate and store the water-soluble drug model sodium fluorescein (SF) and can release the encapsulated SF by moving the pen tip across the surface. The results show that the marker pen can release a constant amount of SF at the nanogram level per unit length of the line drawn with the pen, and the cumulative SF release amount has a linear relationship with the length of the line. In addition, the amount of released SF is linear with respect to the SF concentration in the aqueous solution. Moreover, the SF-filled marker pen has excellent long-term stability as evidenced by that the amount of SF released from the pen remains constant within two weeks after filling.

Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.

Effects of Polyvinylpyrrolidone and Ethyl Cellulose in Polyurethane Electrospun Nanofibers on Morphology and Drug Release Characteristics.

Polyurethanes (PUs) are a popular choice for composing nanofibers due to their spinnability, biocompatibility, high chemical stability, and good mechanical and elasticity properties. The desired release behaviors are also achieved by using combinations of PUs and various polymers. In this study, we investigated effects of polyvinylpyrrolidone (PVP) and ethyl cellulose (EC) on PU electrospun nanofibers in terms of morphological structures and drug release characteristics. Nanofibers were prepared using blends of PU with either EC or PVP in different ratios by electrospinning. The effects of PVP or EC on the morphology and diameter of the prepared nanofibers were examined with scanning electron microscope (SEM). The compatibility of the components used in the formulations of nanofibers was determined by attenuated total reflection (ATR)-fourier-transform infrared (FTIR). Donepezil hydrochloride (DNP), a water soluble compound, was selected as a model drug to examine its release characteristics from both PU/PVP and PU/EC electrospun nanofibers. In vitro drug release studies from electrospun nanofibers were performed according to the method defined in the monograph as the "paddle over disk method" of United States Pharmacopeia 38. The SEM images showed that addition of EC or PVP to PU solutions did not affect the generation of nanofibers, and those formed had a smooth surface without beads in nanoscale. The ATR-FTIR spectra disclosed that EC and PVP were separately incorporated into the PU matrix. The in vitro release data indicated that the presence of EC or PVP in PU nanofibers dramatically changed the release behavior of DNP. PU/EC nanofibers (F4) provided sustained drug release with the Korsmeyer-Peppas drug release kinetic mechanism, in which the release rate was controlled by diffusion of the drug, while all of the PU/PVP nanofibers exhibited fast drug release. Overall, these characteristics of PU/EC (10/8) electrospun nanofibers has suggested their potential use as a drug carrier from which water-soluble drug release may occur in a sustained fashion.

Formulation and evaluation of Psyllium Husk-containing granules as a carrier to sustain the release of Water-Soluble drugs II

In previous work, the use of psyllium huskas the main component of sustained release preparations, was investigated. Granules of Metformin HCl containing different hydrocolloids namely; psyllium Husk and sodium carboxy-methyl cellulose (Na CMC), “System I”, and granules of sodium salicylate containing these hydrocolloids in addition to stearic acid, “System II’ were prepared. In vitro release studies in phosphate buffer solution (pH 6.8) clearly revealed the superiority of psyllium husk and Na CMCcombination in sustaining the release of both drugs. The introduction of stearic acid in formulations SC5 and SP5 have, significantly, slowed down the release of Sodium salicylate to 46% and 53%, respectively, after 7 hours. Mathematical modeling of the release data revealed that the release mechanism which describes the diffusion of both drugs from these systems is driven by a complex behavior such as swelling, matrix erosion as well as diffusion through the swollen matrix of most formulations. Evaluation of the drug release mechanism from these systems suggested that the release could be described by a complex mechanism, which may involve First-order kinetics, Higuchi diffusion controlled as well as Korsmeyer Peppas models

The Correlation between Physical Crosslinking and Water-Soluble Drug Release from Chitosan-Based Microparticles.

Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan glutamate and beta-glycerophosphate as an ion crosslinker (CF). The Box–Behnken design was applied to optimize the microparticles in terms of their drug loading and release behavior. Physicochemical studies were undertaken to support the results from dissolution tests and to evaluate the impact of the crosslinking ratio on the microparticles’ characteristics. The zidovudine dissolution behavior had a complex nature which comprised two phases: an initial burst effect followed with a prolonged release stage. The initial drug release, which can be modulated by the crosslinking degree, was primarily governed by the dissolution of the drug crystals located on the microparticles’ surfaces. In turn, the further dissolution stage was related to the drug diffusion from the swollen polymer matrix and was found to correlate with the drug loading. Differential Scanning Calorimetry (DSC) studies revealed the partial incorporation of a non-crystallized drug within the polymer matrix, which correlated with the amount of CF. Although CF influenced the swelling capacity of chitosan glutamate microparticles, surprisingly a higher amount of CF did not impact the time required for 80% of the drug to be released markedly. The formulation with the lowest polymer:CF ratio, 3:1, was selected as optimal, providing satisfactory drug loading and displaying a moderate burst effect within the first 30 min of the study, followed with a prolonged drug release of up to 210 min.

Carboxymethyl cellulose/mesoporous magnetic graphene oxide as a safe and sustained ibuprofen delivery bio-system: Synthesis, characterization, and study of drug release kinetic

The designing and preparation of a safe drug carrier with sustained and controlled poorly water-soluble drug release ability is valuable in medicine. By considering this aim, magnetic graphene oxide (MG) was prepared through the co-precipitation of the Fe3+ and Fe2+ ions on the graphene oxide (GO) surface. The prepared MG was coated with mesoporous silica (MG@mSiO2). Ibuprofen (IBU) as a poorly water-soluble drug was loaded into the MG@mSiO2 nanosystem and MG@mSiO2-IBU was obtained. MG@mSiO2-IBU showed the burst drug release behavior and released about 86 % of IBU in the first 2 h. To overcome this burst release of IBU, carboxymethyl cellulose (CMC) was used as a coating agent for the encapsulation of MG@mSiO2-IBU. Drug release studies showed that CMC-coated MG@mSiO2-IBU (CMC/MG@mSiO2-IBU) sustainably released the IBU in 8 h with a first-order kinetic model. MG@mSiO2 and CMC/MG@mSiO2-IBU were characterized by using various techniques. VSM analysis displayed the superparamagnetic properties for the CMC/MG@mSiO2-IBU. Based on the MTT and drug release investigation results the prepared CMC/MG@mSiO2-IBU bio-nanocomposite could be proposed potentially as a safe carrier with controlled release of the poorly water-soluble IBU drug.

Application of Eudragit RS 30D as a Potential Drug Release Retardant of Acetaminophen and Caffeine for Prolonged Duration of Comfort

The objective of the study is to formulate an extended release matrix tablet dosage form containing acetaminophen and caffeine by applying polymer technology which will relieve all kinds of pain for about 12 hours. Considering the fact that there is no such formulation available in the pharmaceutical market, it is expected that this drug could be an effective introduction. Hydrophobic polymers have a great application in pharmaceutical sciences as they retard the release of water-soluble drugs and give prolonged effect. Eudragit RS 30D was used to prepare 3 formulations (EF1, EF2, and EF3) containing varying concentrations of polymer, through the wet granulation method. Each tablet contained 1000 mg of acetaminophen and 130 mg of caffeine including other suitable excipients. All pharmacopeial and nonpharmacopeial tests were conducted to determine the quality of dosage form and to identify optimized formulation among EF1-EF3. Dissolution was conducted on similar gastric conditions through which different kinetic models were applied using DDSolver. For 12 hrs of dissolution, caffeine was released from EF1, EF2, and EF3 with the percentage release in the range from 99.85% to 100.65%, 99.32% to 100.28%, and 98.09% to 100.77%, respectively. For acetaminophen, the percent release was from 99.81% to 100.91%, 100.24% to 100.91%, and 86.81% to 95.73% for EF1-EF3, respectively. Results concluded that EF2 is the most optimized drug having all physicochemical quality control tests within the specified limits. On applying different models like zero-order, Hixson-Crowell, Higuchi, and Korsmeyer-Peppas upon use, it is concluded that the formulation follows Korsmeyer-Peppas as it was the best-fitted model with the r2 value closest to 0.999. EF2 is considered as a potential drug to be manufactured that will give prolonged relief against pain and will decrease compliance issues related to dosing frequency.

Long time release of water soluble drug from hydrophilic nanofibrous material

ABSTRACTIn this study, mesoporous silica nanoparticles (MSNs) were embedded into the hydrophilic poly(vinyl alcohol) (PVA) nanofibrous mats to achieve sustained release of water soluble drug from hydrophilic nanofibrous mats. MSNs were successfully prepared based on a sol–gel method. Water soluble drug naproxen sodium was then loaded into the mesopores of the MSNs, and different amounts of the drug‐loaded MSNs were further incorporated into the fibers by the electrospinning process. Morphology of the nanofibrous mats was investigated, and it was found that all the fibers exhibited fibrous structure. Interestingly, lots of protrusions could be observed from the scanning electron microscopy images with high magnification, and numbers of the protrusions increased with the increasing of loading ratios of the MSNs from 5 to 15%. In addition, the wetting behaviors of the nanofibrous mats were also measured, and the water contact angles of all the mats were measured to be 0°. Finally, the drug release results indicated that all the PVA/MSNs composite nanofibrous mats showed an obviously prolonged drug release. The optimal loading ratio of the MSNs in the nanofibers was 10% due to the slowest drug release rate. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47922.

Microparticles for sustained release of water-soluble drug based on a containment, dry coating technology.

Controlled release microparticles in a sub-gram-scale batch were fabricated using a ball mill, dry coating technique, to coat the water-soluble core material. This process also guaranteed the maintenance of the containment's integrity during the dry coating process. Quinine (average diameter, ca. 10 μm) and carnauba wax were used as the core and coating material, respectively. We evaluated the influence of process time, milling speed, and quinine-to-carnauba wax ratio on the particle size of the coated particles and their in vitro drug release profiles. Scanning electron microscopic observations suggested that the small wax particles attached to the core (quinine) particles resulted in a smooth film during the dry coating process. The size distribution of the coated particles agreed with the theoretically estimated size distribution. The in vitro release test demonstrated that the coated particles released quinine over 2 h in a biphasic mode. These results suggest that dry coating of microparticles less than 50 µm (D99) is feasible on a several-grams-batch scale. This new ball mill-coating technique also enables a guaranteed containment, a prerequisite for the manufacturing of highly bioactive or biohazard substances.

Electrospinning of calcium phosphate-poly (d,l-lactic acid) nanofibers for sustained release of water-soluble drug and fast mineralization.

Calcium phosphate-based biomaterials have been well studied in biomedical fields due to their outstanding chemical and biological properties which are similar to the inorganic constituents in bone tissue. In this study, amorphous calcium phosphate (ACP) nanoparticles were prepared by a precipitation method, and used for preparation of ACP-poly(d,l-lactic acid) (ACP-PLA) nanofibers and water-soluble drug-containing ACP-PLA nanofibers by electrospinning. Promoting the encapsulation efficiency of water-soluble drugs in electrospun hydrophobic polymer nanofibers is a common problem due to the incompatibility between the water-soluble drug molecules and hydrophobic polymers solution. Herein, we used a native biomolecule of lecithin as a biocompatible surfactant to overcome this problem, and successfully prepared water-soluble drug-containing ACP-PLA nanofibers. The lecithin and ACP nanoparticles played important roles in stabilizing water-soluble drug in the electrospinning composite solution. The electrospun drug-containing ACP-PLA nanofibers exhibited fast mineralization in simulated body fluid. The ACP nanoparticles played the key role of seeds in the process of mineralization. Furthermore, the drug-containing ACP-PLA nanofibers exhibited sustained drug release which simultaneously occurred with the in situ mineralization in simulated body fluid. The osteoblast-like (MG63) cells with spreading filopodia were well observed on the as-prepared nanofibrous mats after culturing for 24 hours, indicating a high cytocompatibility. Due to the high biocompatibility, sustained drug release, and fast mineralization, the as-prepared composite nanofibers may have potential applications in water-soluble drug loading and release for tissue engineering.

Inkjet deposition of itraconazole onto poly(glycolic acid) microneedle arrays.

Poly(glycolic acid) microneedle arrays were fabricated using a drawing lithography process; these arrays were modified with a drug release agent and an antifungal agent by piezoelectric inkjet printing. Coatings containing poly(methyl vinyl ether-co-maleic anhydride), a water-soluble drug release layer, and itraconazole (an antifungal agent), were applied to the microneedles by piezoelectric inkjet printing. Microscopic evaluation of the microneedles indicated that the modified microneedles contained the piezoelectric inkjet printing-deposited agents and that the surface coatings were released in porcine skin. Energy dispersive x-ray spectrometry aided in confirmation that the piezoelectric inkjet printing-deposited agents were successfully applied to the desired target areas of the microneedle surface. Fourier transform infrared spectroscopy was used to confirm the presence of the component materials in the piezoelectric inkjet printing-deposited material. Itraconazole-modified microneedle arrays incubated with agar plates containing Candida albicans cultures showed zones of growth inhibition.

Nanogel-electrospinning for controlling the release of water-soluble drugs

Application of electrospun fibers for the purpose of loading and controlled release of water-soluble drugs remains a challenge due to their low carrying effect as well as quick and unstable drug release. In this study, we have developed a novel nanogel-electrospinning technology through which more stable loading and prolonged release of water-soluble drugs was achieved. In brief, nanogel particles synthesized from a chloroquine (CQ)-loaded bovine serum albumin (BSA) solution were prepared and then combined with genipin, a crosslinking agent. The nanogel solution was then crosslinked to prepare an electrospinning solution with an inner mesh structure. Finally, the microfibrous membranes were fabricated by electrospinning the solution. Uniform BSA nanogel particles were wrapped in the fiber membrane and the number of particles increased with the increase of BSA and genipin concentrations. In addition to being loaded within the BSA nanogel particles, CQ was distributed in the fibers as well, which could be clearly identified using ultraviolet-visible spectroscopy (UV-Vis). The physical, chemical, and mechanical properties of nanogel-electrospun microfibers were similar to those of microfibers formed through a conventional electrospinning approach. The drug release tests indicated that with the same number of BSA nanogel particles, increased CQ loading resulted in increased initial release of the same. The duration of a single drug release cycle lasted up to 40 days. In conclusion, findings from this study have indicated that nanogel-electrospinning is a convenient and effective technology to achieve controlled long-term release of water-soluble drugs.

Long-term release of water-soluble drugs using microsol-electrospun nanofiber sheets

Long-term release of water-soluble drugs using microsol-electrospun nanofiber sheets

Pectin/anhydrous dibasic calcium phosphate matrix tablets for in vitro controlled release of water-soluble drug

Different pectin/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed in order to obtain controlled release of a water-soluble drug (theophylline). Swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralized water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid), to characterize the matrix tablets. When the pectin/ADCP ratio was ≥0.26 (P1, P2, P3 and P4 tablets) a continuous swelling and low theophylline dissolution rate from the matrices were observed. So, pectin gel forming feature predominated over the ADCP properties, yielding pH-independent drug release behavior from these matrices. On the contrary, pectin/ADCP ratios ≤0.11 (P5 and P6 tablets) allowed to achieve drug dissolution pH dependent. Consequently, the suitable selection of the pectin/ADCP ratio will allow to tailor matrix tablets for controlled release of water-soluble drugs in a specific manner in the gastrointestinal tract.

Hairy polymeric nanocapsules with ph-responsive shell and thermoresponsive brushes: Tunable permeability for controlled release of water-soluble drugs

The hairy poly(methacrylic acid-co-divinylbenzene)-g-poly(N-isopropylacrylamide) (P(MAA-co-DVB)-g-PNIPAm) nanocapsules with pH-responsive P(MAA-co-DVB) inner shell and temperature-responsive PNIPAm brushes were prepared by combined distillation–precipitation copolymerization and surface thiol-ene click grafting reaction using 3-(trimethoxysilyl)propyl methacrylate-modified silica (SiO2-MPS) nanospheres as a sacrificial core material. The well-defined PNIPAm was synthesized by a reversible addition fragmentation chain transfer (RAFT) polymerization. The chain end was converted to a thiol by chemical reduction. The PNIPAm was integrated into the nanocapsules via thiol-ene click reaction. The surface thiol-ene click reaction conduced to tunable grafting density of PNIPAm brushes. The grafting densities decreased from 0.70 chains nm−2 to 0.15 chains nm−2 with increasing the molecular weight of grafted PNIPAm chains. Using water soluble doxorubicin hydrochloride (DOX·HCl) as a model molecular, the tunable shell permeability of the nanocapsule was investigated in detail. The permeability constant can be tuned by controlling the thickness of the P(MAA-co-DVB) inner shell, the grafting density of PNIPAm brushes, and the environmental pH and temperature. The tunable shell permeability of these nanocapsules results in the release of the loaded guest molecules with manipulable releasing kinetics. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2202–2216