Controlled Release Characteristics Research Articles

Oral Nanomedicine Based on Multicomponent Microemulsions for Drug-Resistant Breast Cancer Treatment.

The aim of this study is to demonstrate the enhanced therapeutic efficacy of anticancer drugs on drug-resistant breast cancer using multicomponent microemulsions (ECG-MEs) as an oral delivery system. The etoposide-loaded ECG-MEs were composed of coix seed oil and ginsenoside Rh2 (G-Rh2), both of which possess not only the synergistic antitumor effect with etoposide, but also have excipient-like properties. Orally administrated ECG-MEs were demonstrated to be able to accumulate at the tumor site following crossing the intestines as intact vehicles into the blood circulation. The spatiotemporal controlled release characteristics of ECG-MEs brought about the efficient P-gp inhibition by the initially released G-Rh2 and the increased intracellular accumulation of the sequentially released etoposide. The combination antitumor activity of etoposide, G-Rh2 and coix seed oil using ECG-MEs was verified on the xenograft drug-resistant breast tumor mouse models. In addition, the safety evaluation studies indicated that treatment with ECG-MEs did not cause any significant toxicity in vivo. These findings suggest that ECG-MEs as an oral formulation may offer a promising strategy to treat the drug-resistant breast cancer.

Encapsulation of Ethylene Gas into Granular Cold-Water-Soluble Starch: Structure and Release Kinetics.

Ethylene gas was introduced into granular cold-water-soluble (GCWS) starches using a solid encapsulation method. The morphological and structural properties of the novel inclusion complexes (ICs) were characterized using scanning electron microscopy, X-ray diffractometry, and Raman spectroscopy. The V-type single helix of GCWS starches was formed through controlled gelatinization and ethanol precipitation and was approved to host ethylene gas. The controlled release characteristics of ICs were also investigated at various temperature and relative humidity conditions. Avrami's equation was fitted to understand the release kinetics and showed that the release of ethylene from the ICs was accelerated by increasing temperature or RH and was decelerated by increased degree of amylose polymerization. The IC of Hylon-7 had the highest ethylene concentration (31.8%, w/w) among the five starches, and the IC of normal potato starch showed the best controlled release characteristics. As a renewable and inexpensive material, GCWS starch is a desirable solid encapsulation matrix with potential in agricultural and food applications.

Chitosan: A Multifunctional Polymer

Chitin is the most important natural polysaccharide after cellulose, found in crustaceous shell or in cell walls of fungi. Chitosan, one of the natural multifunctional polymers, due to its unique and versatile biological properties is regarded as a useful compound in medical and pharmaceutical technology. In recent times chitosan has been far and wide used as a popular formulation excipient due to its inimitable characteristics in the field of pharmaceutical sciences as binding, disintegrating, stabilizing, suspending, tablet coating, and film forming material. Recently, considerable research effort has been made in order to develop safe and efficient chitosan products. Chitosan has been comprehensively investigated for its suitability for its controlled release characteristics in various studies. Oral delivery of genes and peptides by means of different formulations based on chitosan is also investigated in various examinations by the capability of its absorption and penetration enhancing properties. It is possessing tremendous mucoadhesive and inherent anti-microbial properties, so that it can be used as a carrier for novel drug delivery. In addition to the above mentioned reasons, tailoring the controlled release and to improve the therapeutic efficacy of the low molecular weight drug compounds can also be achieved by this polymer and moreover in combination with various polymers is feasible due its compatibility i.e. low chemical reactivity. This brief editorial epitomizes the potential applications of chitosan in novel drug delivery systems.

RGD conjugated liposome-hollow silica hybrid nanovehicles for targeted and controlled delivery of arsenic trioxide against hepatic carcinoma

The aim of our study was to construct an Arg-Gly-Asp (RGD)-conjugated liposome-hollow silica hybrid nanovehicle for targeted delivery and controlled release of arsenic trioxide (ATO), whose anti-solid tumor effect was hampered by poor pharmacokinetics and dose-limited toxicity. Hydrophobic interactions were used to attach intact lipid membrane to the surface of chlorodimethyloctadecylsilane-modified hollow mesoporous silica nanoparticles. The prepared nanovehicles (RGD-LP-CHMSN) were characterized for uniform structure (silica core of ∼140nm in diameter and liposomal shell of ∼6nm), comparable drug loading efficiency (6.76%), desirable stability and strengthened controlled release. In vitro, RGD-LP-CHMSN showed good biocompatibility and low toxicity on HepG2, MCF-7 and LO2 cells. The targeted delivery of ATO by nanocarriers (RGD-LP-CHMSN-ATO) was demonstrated by an enhanced cellular uptake and a reduced half maximal inhibitory concentration (IC50) value. In pharmacokinetic studies, the RGD-LP-CHMSN-ATO group, compared to the free ATO group, prolonged the half time (t1/2β) by 1.7 times and increased the area under curve (AUC) by 2.4 times. In addition, in a H22 tumor-xenograft mouse model, nanovehicles improved the targeting efficiency and anticancer potential of ATO. In conclusion, the strategy of constructing a nanocarrier with targeted delivery and controlled release characteristics is prospective to enhance the antitumor effect of ATO.

Systematic development of a gastroretentive fixed dose combination of lamivudine and zidovudine for increased patient compliance

The present study describes systematic development of a gastroretentive bilayer tablet formulation containing fixed dose combination of lamivudine and zidovudine exhibiting controlled drug release and floating-bioadhesive characteristics. Effervescent floating-bioadhesive bilayer tablets containing rational blend of polymers were formulated by non-aqueous granulation employing isopropyl alcohol. A face centred cubic design was employed for optimizing various critical material attributes of the bilayer tablets, which were evaluated for bioadhesive strength (BS), buoyancy time (Tb) and drug release characteristics as the critical quality attributes for each layer. The optimum composition for each layer was selected by “trading off” the magnitude of various quality attributes by maximization of BS, Tb and drug release characteristics, and demarcated in the design space. Gamma scintigraphic studies in healthy volunteers indicated gastroretentive behaviour of the optimized formulation upto 6 h, while the marketed immediate release formulation taken as control showed maximum gastroretentivity only upto 1 h. In a nutshell, these studies corroborated development of an optimal and stable once-a-day controlled release gastroretentive system of lamivudine and zidovudine.

Polyunsaturated fatty acid-based targeted nanotherapeutics to enhance the therapeutic efficacy of docetaxel

Since breast cancer is one of the most lethal malignancies, targeted strategies are urgently needed. In this study, we report the enhanced therapeutic efficacy of docetaxel (DTX) when combined with polyunsaturated fatty acids (PUFA) for effective treatment of multi-resistant breast cancers. Folic acid (FA)-conjugated PUFA-based lipid nanoparticles (FA-PLN/DTX) was developed. The physicochemical properties, in vitro uptake, in vitro cytotoxicity, and in vivo anticancer activity of FA-PLN/DTX were evaluated. FA-PLN/DTX could efficiently target and treat human breast tumor xenografts in vivo. They showed high payload carrying capacity with controlled release characteristics and selective endocytic uptake in folate receptor-overexpressing MCF-7 and MDA-MB-231 cells. PUFA synergistically improved the anticancer efficacy of DTX in both tested cancer cell lines by inducing a G2/M phase arrest and cell apoptosis. Combination of PUFA and DTX remarkably downregulated the expression levels of pro-apoptotic and anti-apoptotic markers, and blocked the phosphorylation of AKT signaling pathways. Compared to DTX alone, FA-PLN/DTX showed superior antitumor efficacy, with no signs of toxic effects in cancer xenograft animal models. We propose that PUFA could improve the therapeutic efficacy of anticancer agents in cancer therapy. Further studies are necessary to fully understand these findings and achieve clinical translation.

Carobomer Based Controlled Release Designs of Atorvastatin Calcium Tablets Evaluated Using Quality by Design (QbD) Approach

The study carried out here was focused on developing conventional monolithic controlled release matrix tablet of Atorvastatin calcium using carbomer as release controlling polymer. This system ensures the drug release at the alkaline pH region where the drug has got maximum solubility. Further the study was concentrated on comparing the impact of gelling agent polyvinyl pyrrolidone on drug release. Quality by design tools were considered during formulation development and the polymer concentrations were optimized adopting the statistical tool, design of experiments (DoE). The optimized formulation of present study exhibited desired controlled drug release characteristics in the alkaline pH conditions and at acidic environment the drug dissolution was minimal as intended.

FORMULATION, OPTIMIZATION, AND CHARACTERIZATION OF BIOCOMPATIBLE INHALABLE D-CYCLOSERINE-LOADED ALGINATE-CHITOSAN NANOPARTICLES FOR PULMONARY DRUG DELIVERY

<p>ABSTRACT<br />Objective: To prepare Nanoparticulate dosage form having improved drug bioavailability and reduced dosing frequency of antitubercular drugs<br />which will helps in improving patient compliance in the treatment of multi-drug resistant tuberculosis (MDR-TB).<br />Methods: Ionotropic gelation method was used to prepare D-cycloserine (D-CS)-loaded alginate-chitosan nanoparticles, and the particles are<br />characterized by their particle size and morphology using particle size analyzer and scanning electron microscopy (SEM). X-ray diffraction (XRD),<br />differential scanning calorimetry (DSC), and Fourier-transformed infrared (FTIR) studies were used to determine drug-polymer interactions and drug<br />entrapment. Entrapment efficiency, drug loading (DL), particle size, and zeta potential of nanoparticles were also studied. The 2<br /> factorial designs of<br />experiments by Design-Expert<br />®<br /> V9 were used to optimize the particle size and entrapment efficiency of nanoparticles.<br />Results: The optimized batch had shown the entrapment efficiency of 98.10±0.24% and DL of 69.32±0.44% with particle size and zeta potential<br />as 344±5 nm and −42±11.40 mV, respectively. DSC, FTIR, and XRD studies confirmed the drug entrapment within nanoparticle matrix. SEM results<br />showed spherical-shaped particles. Sustained release of drug from the nanoparticles was observed for 24 hrs period. Respirable fraction up to<br />52.37±0.7% demonstrates the formulation suitability for deep lung delivery. Lung inflammatory study showed a less inflammatory response.<br />Conclusion: Ionotropic gelation method can be used to prepare biocompatible particles with a high entrapment efficiency, DL, optimum particle size,<br />and controlled release characteristics, which can serve as a convenient delivery system for D-CS and could be a potential alternative to the existing<br />conventional therapy in MDR-TB.<br />Keywords: Nanoparticles, Alginate, Chitosan, Inhalation, Sustained release, Tuberculosis.<br />3</p>

Dual pH-Mediated Mechanized Hollow Zirconia Nanospheres.

We demonstrate for the first time how to assemble mechanized hollow zirconia nanospheres (MHzNs), consisting of hollow mesoporous zirconia nanospheres (HMZNs) as nanoscaffolds and supramolecular switches anchored on the exterior surface of HMZNs. The remarkable advantage of substitution of HMZNs for conventional mesoporous silica nanoscaffolds is that HMZNs can suffer the hot alkaline reaction environment, which provides a novel strategy for functionalization and thus achieve dual pH-mediated controlled release functions by simple and practicable assembly procedure. Under neutral solution, cucurbituril[7] (CB[7]) macrocycles complexed with propanone bis(2-aminoethyl)ketal (PBAEK) to form [2]pseudorotaxanes as supramolecular switches, blocking the pore orifices and preventing the undesirable leakage of cargoes. When solution pH was adjusted to alkaline range, CB[7] macrocycles, acting as caps, disassociated from PBAEK stalks and opened the switches due to the dramatic decrease of ion-dipole interactions. While under acidic conditions, PBAEK stalks were broken on account of the cleavage of ketal groups, resulting in the collapse of supramolecular switches and subsequent release of encapsulated cargoes. MHzNs owning dual pH-mediated controlled release characteristic are expected to apply in many fields. In this work, the feasibility of doxorubicin (DOX)-loaded MHzNs as targeted drug delivery systems was evaluated. In vitro cellular studies demonstrate that DOX-loaded MHzNs can be easily taken up by SMMC-7721 cells, can rapidly release DOX intracellularly, and can enhance cytotoxicity against tumor cells, proving their potential for chemotherapy.

Novel Solid Encapsulation of Ethylene Gas Using Amorphous α-Cyclodextrin and the Release Characteristics.

This research investigated the encapsulation of ethylene gas into amorphous α-cyclodextrins (α-CDs) at low (LM) and high (HM) moisture contents at 1.0-1.5 MPa for 24-120 h and its controlled release characteristics at 11.2-52.9% relative humidity (RH) for 1-168 h. The inclusion complexes (ICs) were characterized using X-ray diffractometry (XRD), nuclear magnetic resonance spectroscopy (CP-MAS (13)C NMR), and scanning electron microscopy (SEM). Ethylene concentrations in the ICs were from 0.45 to 0.87 mol of ethylene/mol CD and from 0.42 to 0.54 mol of ethylene/mol CD for LM and HM α-CDs, respectively. Ethylene gas released from the encapsulated powder at higher rates with increasing RH. An analysis of release kinetics using Avrami's equation showed that the LM and HM amorphous α-CDs were not associated with significant differences in release constant k and parameter n for any given RH condition. NMR spectra showed the presence of the characteristic carbon-carbon double bond of ethylene gas in the encapsulated α-CD powder.

Duodenum-triggered delivery of pravastatin sodium: II. Design, appraisal and pharmacokinetic assessments of enteric surface-decorated nanocubosomal dispersions

Context: Pravastatin sodium (PVS) is a freely water-soluble HMG-CoA inhibitor that suffers from instability at gastric pH, extensive first pass metabolism, short elimination half-life (1–3 h) and low oral bioavailability (18%). Objective: To overpower these drawbacks and to maximize drug absorption at its main site of absorption at the duodenum, enteric surface-coated PVS-loaded nanocubosomal dispersions were presented. Materials and methods: Glyceryl monooleate (GMO)-based dispersions were developed by the fragmentation or the liquid precursor methods using Pluronic® F127 or Cremophor® EL as surfactants. As a challenging enteric-coating approach, the promising dispersions were surface-coated via lyophilization with Eudragit® L100-55; a duodenum-targeting polymer. The drug content, particle size, zeta potential, morphology and release studies of PVS-loaded dispersions were evaluated before and after surface-coating. Compared to an aqueous PVS solution, the pharmacokinetics of the best achieved system (E-F8) was evaluated (UPLC-MS/MS) in rats. Results: The enteric surface-coated nanocubosomal dispersions were more or less spherical in shape and showed high drug-loading, negative zeta potential values and fine-tuned biphasic drug-release patterns characterized by retarded (2 h) and sustained (10 h) phases in pH 1.2 and pH 6.8, respectively. E-F8 system showed significantly (p< 0.05) higher oral bioavailability, delayed Tmax and prolonged MRT0−∞ following oral administration in rats. Conclusions: The duodenum-triggering potential and the controlled-release characteristics of the best achieved system for smart PVS delivery were revealed.

Xanthan Gum Coated Mucoadhesive Liposomes for Efficient Nose to Brain Delivery of Curcumin

Background: The objective of this study was to develop liposomal mucoadhesive drug delivery system for the delivery of curcumin via nasal route, to avoid hepatic first pass metabolism, to increase residence time and to investigate its nose to brain delivery potential. Methodology: The liposomes were prepared by solvent dispersion method using soya lecithin and cholesterol as a lipid phase and xanthan gum as a mucoadhesive polymer. The liposomes were evaluated for particle size, entrapment efficiency, mucoadhesion, DSC, ex vivo permeation, histopathological study, in vitro drug release, and in vivo study for the estimation of drug in brain after intranasal administration. Results and Discussion: The particle size was in the range of 100.2-150 nm with good stability and controlled release characteristics without any deleterious effect on nasal mucosa of rat. When administered via intranasal route the liposomes showed higher drug distribution in brain (1240 ng) compared to drug solution (65 ng). Conclusion: The results of the in vivo study suggests that the xanthan gum coated curcumin liposomes is a promising drug delivery system to deliver drug to the brain through nasal route. Keywords: Curcumin, liposomes, mucoadhesion, nose to brain delivery, solvent dispersion method, xanthan gum.

Preparation and characterization of magnetic thermosensitive fluorouracil micelles

In this study, we synthesized P(NIPAM-co-DMAM)-b-PLA polymers with free radical polymerization and ring-opening addition polymerization, and immediately assembled ‘dextran magnetic layered double hydroxide fluorouracil’ (DMF) magnetic particles into the core of the amphiphilic polymer micelles with synchronous hydration and dialysis, to generate a magnetic thermosensitive fluorouracil drug delivery system. The basic properties of the micelle particles, such as the core–shell-type structure, size, and zeta potential, were studied with 1H-NMR, FTIR, TEM, TGA, laser nanoparticle size analysis, and other characterization techniques. The thermosensitivity of the micelles was investigated by measuring parameters such as the lower critical solution temperature (LCST) and the relationship between the particle size variation and temperature. The drug release curves for the micelles at different temperatures were constructed with a dialysis method. The LCST of the triblock polymers was 42 °C. The particle sizes of the blank micelles and DMF-loaded micelles were 493.6 ± 1.8 nm and 464.9 ± 4.1 nm, respectively, at 25 °C. When the temperature was higher than LSCT, a contraction phase change in the micelle structure occurred, a significant characteristic of the core–shell-type structure, and reversible phase transition phenomena. The release behavior of the drug-loaded micelles showed obvious variations with temperature. Therefore, the magnetic thermosensitive fluorouracil drug delivery system has a good magnetic response and excellent temperature controlled release characteristics, so it can be used as a drug delivery system in magnetically and thermally targeted chemotherapy for tumors.

Facile preparation of acrylamide grafted locust bean gum-poly(vinyl alcohol) interpenetrating polymer network microspheres for controlled oral drug delivery

Hybridization of natural and synthetic polymers is used to improve the physicochemical stability, swelling and drug release pattern of the respective materials in biological condition. In present study, a biodegradable, biocompatible and stable interpenetrating polymer network (IPN) of acrylamide grafted locust bean gum (Am-g-LBG) and poly(vinyl alcohol) (PVA) was developed by emulsion crosslinking method for spatial and temporal drug delivery. The IPN microspheres were prepared with the help of glutaraldehyde as a crosslinker for controlled oral delivery of buflomedil hydrochloride. The formulation parameters were optimized in terms of different gum:PVA ratio, crosslinker amount and drug loading. The microspheres were evaluated for their drug entrapment efficiency, particle size, swelling, SEM, FTIR, NMR, DSC, XRD and in vitro drug release profile. The particles showed well controlled release characteristics and continued to drug release following diffusion controlled release pattern. The drug release was for prolong time without collapsing the particle matrix. Thus, IPN microspheres based delivery system can be a better approach for controlled delivery of highly water soluble drugs like buflomedil hydrochloride.

Sustained release of risperidone from biodegradable microspheres prepared by in-situ suspension-evaporation process

Risperidone-loaded poly (d,l-lactide-co-glycolide) (PLGA) microspheres were prepared with a suspension-evaporation process with an aqueous suspension containing an in situ-formed aluminum hydroxide inorganic gel (SEP-AL process) and evaluated for encapsulation efficiency, particle size, surface morphology, glass transition temperature, in vitro drug release profile, and in vivo behavior. The SEP-AL microspheres were compared with conventional oil-in-water (O/W) emulsion solvent evaporation method using polyvinylalcohol (PVA) as an emulsifier (CP-PVA process). The microspheres were spherical in shape. DSC measurements showed that risperidone crystallinity was greatly reduced due to the homogeneous distribution of risperidone in PLGA microspheres. In vitro drug release profile from the microspheres showed a sigmoidal pattern of negligible initial burst up to 24h and minimal release (time-lag) for 7days. After the lag phase, slow release took a place up to 25days and then rapid release occurred sharply for 1 week. In vivo rat pharmacokinetic profile from the microspheres showed very low blood concentration level at the initial phase (up to 24h) followed by the latent phase up to 21days. At the 3rd week, main phase started and the blood concentration of the drug increased up to the 5th week, and then gradually decreased. The risperidone-loaded PLGA microspheres produced by SEP-AL process showed excellent controlled release characteristics for the effective treatment of schizophrenia patients.

Preparation and evaluation of ziprasidone-phospholipid complex from sustained-release pellet formulation with enhanced bioavailability and no food effect.

The purpose of this work was to develop ziprasidone-phospholipid complex (ZIP-PLC) in sustained-release pellets to enhance the oral bioavailability and overcome the food effect of ziprasidone. Ziprasidone-phospholipid complex was formulated by solvent-evaporation method. The complexes were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and solubility testing. The optimized ZIP-PLC was used to prepare ZIP-PLC sustained-release pellets via extrusion-spheronization method. The pellets were characterized by in vitro drug-release studies and administered to fasted and fed beagle dogs, and their pharmacokinetics were compared with commercial formulation Zeldox capsule as a control. The results of FTIR, SEM, DSC and PXRD studies confirmed the formation of phospholipid complex. Solubility studies showed there was a higher solubility in water for ZIP-PLC than monohydrate ziprasidoe. The in vitro release rate of ziprasidone from the ZIP-PLC sustained-release pellet exhibited controlled-release characteristics with over 95% total release in 12 h. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolong actions, and no food effect was achieved simultaneously in ZIP-PLC sustained-release pellet compared with Zeldox capsule. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.

Continuous preparation of polymer coated drug crystals by solid hollow fiber membrane-based cooling crystallization

A facile way to continuously coat drug crystals with a polymer is needed in controlled drug release. Conventional polymer coating methods have disadvantages: high energy consumption, low productivity, batch processing. A novel method for continuous polymer coating of drug crystals based on solid hollow fiber cooling crystallization (SHFCC) is introduced here. The drug acting as the host particle and the polymer for coating are Griseofulvin (GF) and Eudragit RL100, respectively. The polymer’s cloud point temperature in its acetone solution was determined by UV spectrophotometry. An acetone solution of the polymer containing the drug in solution as well as undissolved drug crystals in suspension were pumped through the tube side of the SHFCC device; a cold liquid was circulated in the shell side to rapidly cool down the feed solution-suspension in the hollow-fiber lumen. The polymer precipitated from the solution and coated the suspended crystals due to rapid temperature reduction and heterogeneous nucleation; crystals formed from the solution were also coated by the polymer. Characterizations by scanning electron microscopy, thermogravimetric analysis, laser diffraction spectroscopy, X-ray diffraction, Raman spectroscopy, and dissolution tests show that a uniformly coated, free-flowing drug/product can be obtained under appropriate operating conditions without losing the drug’s pharmaceutical properties and controlled release characteristics.

Effect of Coating Thickness on Release Characteristics of Controlled Release Urea Produced in Fluidized Bed Using Waterborne Starch Biopolymer as Coating Material

Loss of granular urea through leaching, ammonia volatilization and denitrification can be overcome by the application of controlled release urea. Sulfur and organic polymers have been used as controlled-release coating materials but they have limitations of high cost, process complexity and environmental issues. Waterborne starch biopolymer modified with polyvinyl alcohol is a cheap, biodegradable and environmentally friendly coating material and is used for the production of controlled release urea in a fluidized bed. The effect of coating thickness is investigated on release time and diffusion coefficient of urea release in distilled water. Release time increases with increase in coating thickness. The diffusion coefficient of nutrient release decreases with increase in coating thickness. However, coating imperfections and porous coating in some cases produced the opposite results both for release time and diffusion coefficient. It is concluded that a significant coating thickness in addition to good uniformity of thickness and film integrity can produce promising controlled release characteristics.

The microfluidic synthesis of composite hollow microfibers for K+-responsive controlled release based on a host-guest system.

A novel type of composite hollow microfiber with K+-responsive controlled-release characteristics based on a host-guest system is prepared by embedding K+-responsive poly(N-isopropylacrylamide-co-acryloylamidobenzo-15-crown-5) (P(NIPAM-co-AAB15C5)) microspheres in the wall of poly(lactic-co-glycolic acid) (PLGA) microfibers as "micro-valves" using a controllable microfluidic approach. By adjusting the volume change of microspheres in response to the environmental K+ concentration, the release rate of the encapsulated drug molecules from the composite hollow microfibers can be flexibly regulated owing to the change in the interspace size between the microfiber wall and microspheres. When the environmental K+ concentration is increased, due to the formation of stable 2 : 1 "sandwich-type" host-guest complexes of 15-crown-5 units and K+ ions, P(NIPAM-co-AAB15C5) microspheres change from a swollen state to a shrunken state. Thus, the interspace size becomes larger, resulting in a rapid increase in the release rate of encapsulated drugs. When the ambient K+ concentration is decreased, the interspace size becomes smaller due to isothermal swelling of microspheres caused by the decreased amount of host-guest complexes, resulting in a decrease in the release rate. The K+-responsive drug release behaviors are reversible. This kind of K+-responsive hollow microfiber with K+-concentration-dependent controlled-release properties provides a new mode in the design of more rational drug delivery systems, which are highly attractive for biomedical applications.

Development and invitro evaluation of infection resistant materials: A novel surface modification process for silicone and Dacron.

Silicone and Dacron are used in a wide spectrum of implantable and indwelling medical products. They elicit a foreign body response, which results in a chronic inflammatory environment and collagenous encapsulation of the medical device that compromises the immune system's ability to effectively fight infections at the biomaterial surface. The objective of this work is to evaluate a novel process to modify silicone and Dacron with a bioactive collagen surface coupled to a gentamicin impregnated hydrogel graft and assess the surface's cytocompatibility and infection resistance properties. Samples of silicone and polyethylene terephthalate (Dacron velour) were modified by plasma deposition and activation followed by a co-polymer acrylic acid (AA)/acrylamide (AAm) hydrogel graft and covalent immobilization of a bioactive collagen surface. The modified surfaces were characterized using FTIR, contact angle, staining, SEM, and XPS. The poly (AA-AAm) hydrogel was impregnated with gentamicin and tested for controlled release characteristics. Each modified surface was evaluated for its ability to resist infection and to promote normal healing as measured by bacterial growth inhibition (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) in both broth and agar conditions as well as using fluorescence microscopy to observe adherence of 3T3-NIH fibroblasts. The addition of the poly (AA-AAm) hydrogel with gentamicin inhibited bacterial growth and the subsequent addition of the collagen surface promoted robust fibroblast adhesion on both silicone and Dacron materials. Thorough surface characterization and invitro bacterial and fibroblast evaluation results suggest that this novel surface bioengineering process generated a highly effective surface on silicone and Dacron with the potential to reduce infection and promote healing.