Surface Modification of Liposomes Using IR700 Enables Efficient Controlled Contents Release Triggered by Near-IR Light.

Stimuli-responsive liposomes are promising drug carriers for cancer treatment because they enable controlled drug release and the maintenance of desired drug concentrations in tumor tissue. In particular, near-IR (NIR) light is a useful stimulus for triggering drug release from liposomes based on its advantages such as deep tissue penetration and safety. Previously, we found that a silicon phthalocyanine derivative, IR700, conjugated to antibodies, can induce the rupture of the cell membrane following irradiation by NIR light. Based on this finding, we constructed IR700-modified liposomes (IR700 liposomes) and evaluated their drug release properties triggered by NIR light. IR700 liposomes released substantial amounts of encapsulated calcein following irradiation by NIR light. Drug release was substantially suppressed by the addition of sodium azide, suggesting that liposomal membrane permeabilization was mediated by singlet oxygen generated from IR700. Moreover, calcein release from IR700 liposomes triggered by NIR light was promoted under conditions of deoxygenation and the presence of electron donors. Thus, membrane disruption should be induced by the physical change of IR700 from highly hydrophilic to hydrophobic as we previously described, although singlet oxygen can cause a certain level of membrane disruption under normoxia. We also observed that doxorubicin-encapsulated IR700 liposomes exhibited significant cytotoxic effects against CT-26 murine colon carcinoma cells following NIR light exposure. These results indicate that IR700 liposomes can efficiently release anti-cancer drugs following NIR light irradiation even under hypoxic conditions and, therefore, they would be useful for cancer treatment.

Development of a novel resin-based dental material with dual biocidal modes and sustained release of Ag+ ions based on photocurable core-shell AgBr/cationic polymer nanocomposites.

Research on the incorporation of cutting-edge nano-antibacterial agent for designing dental materials with potent and long-lasting antibacterial property is demanding and provoking work. In this study, a novel resin-based dental material containing photocurable core-shell AgBr/cationic polymer nanocomposite (AgBr/BHPVP) was designed and developed. The shell of polymerizable cationic polymer not only provided non-releasing antibacterial capability for dental resins, but also had the potential to polymerize with other methacrylate monomers and prevented nanoparticles from aggregating in the resin matrix. As a result, incorporation of AgBr/BHPVP nanocomposites did not adversely affect the flexural strength and modulus but greatly increased the Vicker's hardness of resin disks. By continuing to release Ag+ ions without the impact of anaerobic environment, resins containing AgBr/BHPVP nanoparticles are particularly suitable to combat anaerobic cariogenic bacteria. By reason of the combined bactericidal effect of the contact-killing cationic polymers and the releasing-killing Ag+ ions, AgBr/BHPVP-containing resin disks had potent bactericidal activity against S. mutans. The long-lasting antibacterial activity was also achieved through the sustained release of Ag+ ions due to the core-shell structure of the nanocomposites. The results of macrophage cytotoxicity showed that the cell viability of dental resins loading less than 1.0 wt% AgBr/BHPVP was close to that of neat resins. The AgBr/BHPVP-containing dental resin with dual bactericidal capability and long term antimicrobial effect is a promising material aimed at preventing second caries and prolonging the longevity of resin composite restorations.

In Vitro and In Vivo Evaluation of Targeted Sunitinib-Loaded Polymer Microbubbles Against Proliferation of Renal Cell Carcinoma.

OBJECTIVES: The poor safety profile of sunitinib capsules has encouraged the identification of targeted drug delivery systems against renal cell carcinoma. This study aimed to explore the effect of sunitinib-loaded microbubbles along with ultrasound (US) treatment on proliferation and apoptosis of human GRC-1 granulocyte renal carcinoma cells in vitro and in vivo (xenograft tumor growth in nude mice). METHODS: Liposomes containing sunitinib were prepared by using the transmembrane ammonium sulfate gradient method and then absorbed into polymer microbubbles to generate sunitinib-loaded microbubbles. Entrapment of sunitinib was verified by 25-25-[N-[(7-nitro-2-1,3-benzoxadiazol-4-yl)methyl]amino]-27-norcholesterol staining. GRC-1 cells were treated with microbubbles alone, liposomes alone, sunitinib alone, sunitinib-loaded microbubbles without and with US, and no treatment (control). Cell survival and apoptosis were assessed at 12, 24, and 48 hours after treatment. Xenograft tumors were induced by implantation of GRC-1 cells in nude mice. The animals with tumors were then randomly assigned to sunitinib alone, sunitinib-loaded microbubbles - US, sunitinib-loaded microbubbles + US, and no treatment (control; n = 10 per group). The tumor volumes were analyzed on the 7th, 15th, and 21st days. RESULTS: The sunitinib entrapment efficiency in the liposomes was approximately 78%. The effective sunitinib concentration in each group was 0.1 µg/mL. The sunitinib-loaded microbubble + US group showed a lower in vitro cell survival rate (P < .001) compared with the other groups. Greater in vivo inhibition of xenograft tumor growth was also observed in the sunitinib-loaded microbubble + US group compared with the other groups. CONCLUSIONS: Combined sunitinib-loaded microbubbles and US treatment significantly inhibits growth of renal carcinoma cells both in vitro and in vivo.

Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles.

OBJECTIVES: A protocol was designed to produce albumin-coated microbubbles (MBs) loaded with functionalized polylactide (PLA) nanoparticles (NPs) for future drug delivery studies. METHODS: Microbubbles resulted from the sonication of 5% bovine serum albumin and 15% dextrose solution. Functionalized NPs were produced by mixing fluorescent PLA and PLA-polyethylene glycol-carboxylate conjugates. Nanoparticle-loaded MBs resulted from the covalent conjugation of functionalized NPs and MBs. Three NP/MB volume ratios (1/1, 1/10, and 1/100) and unloaded MBs were produced and compared. Statistical evaluations were based on quantitative analysis of 3 parameters at 4 time points (1, 4, 5, and 6 days post MB fabrication): MB diameter using a circle detection routine based on the Hough transform, MB number density using a hemocytometer, and NP-loading yield based on MB counts from fluorescence and light microscopic images. Loading capacity of the albumin-coated MBs was evaluated by fluorescence. RESULTS: Loaded MB sizes were stable over 6 days after production and were not significantly different from that of time-matched unloaded MBs. Number density evaluation showed that only 1/1 NP/MB volume ratio and unloaded MB number densities were stable over time, and that the 1/1 MB number density evaluated at each time point was not significantly different from that of unloaded MBs. The 1/10 and 1/100 NP/MB volume ratios had unstable number densities that were significantly different from that of unloaded MBs (P < .05). Fluorescence evaluation suggested that 1/1 MBs had a higher NP-loading yield than 1/10 and 1/100 MBs. Quantitative loading evaluation suggested that the 1/1 MBs had a loading capacity of 3700 NPs/MB. CONCLUSIONS: A protocol was developed to load albumin MBs with functionalized PLA NPs for further drug delivery studies. The 1/1 NP/MB volume ratio appeared to be the most efficient to produce stable loaded MBs with a loading capacity of 3700 NPs/MB.

Smart photothermal-triggered bilayer phase transition in AuNPs-liposomes to release drug.

Novel thermosensitive liposomes with embedded Au nanoparticles (AuNPs) in the liposome bilayer were prepared by a combination method of film build and supercritical CO(2) incubation. These AuNPs-liposomes possess AuNPs that are embedded in the bilayer and a drug that is encapsulated in the central aqueous compartment. The AuNPs in the liposomes can strongly absorb light energy and efficiently convert the absorbed energy to heat. The localized heat induces a phase transition in the liposome bilayer and releases the drug. The drug release from the AuNPs-liposomes can be controlled by the irradiation time and AuNPs concentration in the AuNPs-liposomes at room temperature, where the AuNPs function as a nanoswitch for triggering drug release both spatially and temporally. The results suggest that drug release from the AuNPs-liposomes is due to a photothermic effect that induces phase transition of the liposomes rather than destruction of the liposome bilayer.

Partially polymerized liposomes: stable against leakage yet capable of instantaneous release for remote controlled drug delivery.

A critical issue for current liposomal carriers in clinical applications is their leakage of the encapsulated drugs that are cytotoxic to non-target tissues. We have developed partially polymerized liposomes composed of polydiacetylene lipids and saturated lipids. Cross-linking of the diacetylene lipids prevents the drug leakage even at 40 °C for days. These inactivated drug carriers are non-cytotoxic. Significantly, more than 70% of the encapsulated drug can be instantaneously released by a laser that matches the plasmon resonance of the tethered gold nanoparticles on the liposomes, and the therapeutic effect was observed in cancer cells. The remote activation feature of this novel drug delivery system allows for precise temporal and spatial control of drug release.

Targeting drug delivery with light: A highly focused approach.

Light is a uniquely powerful tool for controlling molecular events in biology. No other external input (e.g., heat, ultrasound, magnetic field) can be so tightly focused or so highly regulated as a clinical laser. Drug delivery vehicles that can be photonically activated have been developed across many platforms, from the simplest "caging" of therapeutics in a prodrug form, to more complex micelles and circulating liposomes that improve drug uptake and efficacy, to large-scale hydrogel platforms that can be used to protect and deliver macromolecular agents including full-length proteins. In this Review, we discuss recent innovations in photosensitive drug delivery and highlight future opportunities to engineer and exploit such light-responsive technologies in the clinical setting.

Temperature/near-infrared light-responsive conductive hydrogels for controlled drug release and real-time monitoring.

Stimuli-responsive hydrogels with adaptable physical properties show great potential in the biomedical field. In particular, the collection of electrical signals is essential for precision medicine. Here, a simple strategy is demonstrated for achieving controlled drug release and real-time monitoring using an interpenetrating binary network consisting of a graphene aerogel and a poly(N-isopropylacrylamide) hydrogel with incorporated polydopamine nanoparticles (PDA-NPs). Owing to the good physical properties of graphene and the embedded PDA-NPs, the hybrid hydrogel shows enhanced mechanical properties and good electrical conductivity. In addition, the hybrid hydrogel also shows dual thermo- and near-infrared light responsiveness, as revealed by the controlled release of a model drug. In addition, as the hydrogel exhibits detectable changes in resistance during drug release, the drug-release behavior of the hydrogel can be monitored in real time using electrical signals. Moreover, owing to the abundance of catechol groups on the PDA-NPs, the hybrid hydrogel shows good tissue adhesiveness, as demonstrated using in vivo experiments. Thus, the developed hybrid hydrogel exhibits considerable practical applicability for drug delivery and precision medicine.

Construction of a Mesoporous Polydopamine@GO/Cellulose Nanofibril Composite Hydrogel with an Encapsulation Structure for Controllable Drug Release and Toxicity Shielding.

The development of intelligent and multifunctional hydrogels having photothermal properties, good mechanical properties, sustained drug release abilities with low burst release, antibacterial properties, and biocompatibility is highly desirable in the biomaterial field. Herein, mesoporous polydopamine (MPDA) nanoparticles wrapped with graphene oxide (GO) were physically cross-linked in cellulose nanofibril (CNF) hydrogel to obtain a novel MPDA@GO/CNF composite hydrogel for controllable drug release. MPDA nanoparticles exhibited a high drug loading ratio (up to 35 wt %) for tetracycline hydrochloride (TH). GO was used to encapsulate MPDA nanoparticles for extending the drug release time and reinforcing the physical strength of the obtained hydrogel. The mechanical strength of the as-fabricated MPDA@GO/CNF composite hydrogel was five times greater compared to that of the pure CNF hydrogel. Drug release experiments demonstrated that burst release behavior was significantly reduced by adding MPDA@GO. The drug release time of the MPDA@GO/CNF composite hydrogel was 3 times and 7.2 times longer than that of the polydopamine/CNF hydrogel and pure CNF hydrogel, respectively. The sustained and controlled drug release behaviors of the composite hydrogel were highly dependent on the proportion of MPDA and GO. Moreover, the rate of drug release could be accelerated by near-infrared (NIR) light irradiation and pH value change. The drug release kinetics of the as-prepared composite hydrogel was well described by the Korsmeyer-Peppas model, and the drug release mechanism of TH from the composite hydrogel was anomalous transport. Importantly, this carefully designed MPDA@GO/CNF composite hydrogel showed good biocompatibility through an in vitro cytotoxicity test. In particular, the toxicity of GO was well shielded by the CNF hydrogel. Therefore, this novel MPDA@GO/CNF composite hydrogel with an encapsulation structure for controllable drug release and toxicity shielding of GO could be used as a very promising controlled drug delivery carrier, which may have potential applications for chemical and physical therapies.

Polylactic acid sealed polyelectrolyte complex microcontainers for controlled encapsulation and NIR-Laser based release of cargo.

Surface mediated drug delivery is important for a large variety of applications, especially in medicine to control cell growth, prevent blood platelet activation on implants or for self-disinfecting devices (e.g. catheters). In industrial applications, controlled release of substances from surfaces is needed in a broad range of applications from anti-corrosion systems to anti-biofouling. Polyelectrolyte multilayers (PEM) based microcontainers (MCs) require several days production time, while MCs composed out of polylactic acid (PLA) are entirely hydrophobic, offering no functionality. We hereby present an approach to fabricate PLA coated synthetic as well as biopolymer based biodegradable polyelectrolyte complex MCs able to encapsulate small hydrophilic cargo within less than one hour. The chambers facilitate laser controlled release of cargo within submerged conditions.

In vitro evaluation of innovative light-responsive nanoparticles for controlled drug release in intestinal PDT.

Nanoparticles (NP) have gained importance as drug delivery systems for pharmaceutical challenging drugs. Their size properties allow passive targeting of cancer tissue by exploiting the enhanced permeability and retention (EPR) effect. Furthermore, surface modifications enable an active drug targeting for diseased regions in the human body. Besides the advantages, the drug release from commonly used biodegradable NP is mostly depending on physiological circumstances. Hence, there is a need for a more controllable drug release. The use of light-responsive polymers is an innovative conception enabling a more distinct drug release by an external light stimulus. The idea provides potential for an increase in efficiency and safety of local therapies. In this study, innovative light-sensitive NP were investigated for a photodynamic therapy (PDT) of gastrointestinal tumors. Nanoparticles based on a newly developed light-responsive polycarbonate (LrPC) and poly(lactic-co-glycolic-acid) (PLGA) were loaded with the approved photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (mTHPC). Mucus penetrating properties were obtained by surface PEGylation of the nanoparticles either by using LrPC in combination with a PEGylated PLA (PEG-PLA) or by a combination with PEGylated LrPC (LrPC-PEG). Cytotoxic potential in dependency of a light-induced drug release was investigated in different cytotoxicity assays. Intracellular accumulation in mucus producing colon-carcinoma cell line HT-29-MTX was analysed by HPLC and confocal laser microscopy.

Drug release responses of zinc ion crosslinked poly(methyl vinyl ether-co-maleic acid) matrix towards microwave.

The drug release characteristics of beads made of poly(methyl vinyl ether-co-maleic acid) using Zn2+ as the crosslinking agent were investigated with respect to the influence of microwave irradiation. The beads were prepared by an extrusion method with sodium diclofenac as a model water-soluble drug. They were subjected to microwave irradiation at 80W for 5 and 20 min, and at 300W for 1 min 20s and 5 min 20s. The profiles of drug dissolution, drug content, drug-polymer interaction and polymer-polymer interaction were determined by dissolution testing, drug content assay, differential scanning calorimetry and Fourier transform infrared spectroscopy. Treatment of beads by microwave at varying intensities of irradiation can aid to retard the drug release with a greater reduction extent through treating the beads for a longer duration of irradiation. The treatment of beads by microwave induced the formation of multiple polymeric domains of great strength and extent of polymer-polymer and drug-polymer interaction. The release of drug from beads was retarded via the interplay of O-H, N-H, C-H, (CH2)n and C-O functional groups of these domains, and was mainly governed by the state of polymer relaxation of the matrix unlike that of the untreated beads of which the release of drug was effected via drug diffusion and polymer relaxation. In comparison to Ca2+ crosslinked matrix which exhibited inconsistent drug release retardation behavior under the influence of microwave, the extent and rate of drug released from the Zn2+ crosslinked beads were greatly reduced by microwave and the release of drug from these beads was consistently retarded in response to both high and low intensity microwaves.

Controlled release of curcumin from poly(HEMA-MAPA) membrane.

In this work, poly(HEMA-MAPA) membranes were prepared by UV-polymerization technique. These membranes were characterized by SEM, FTIR, and swelling studies. Synthesized membranes had high porous structure. These membranes were used for controlled release of curcumin which is already used as folk remedy and used as drug for some certain diseases and cancers. Curcumin release was investigated for various pHs and temperatures. Optimum drug release yield was found to be as 70% at pH 7.4 and 37 °C within 2 h period. Time-depended release of curcumin was also investigated and its slow release from the membrane demonstrated within 48 h.

Increasing Distribution of Drugs Released from In Situ Forming PLGA Implants Using Therapeutic Ultrasound.

One of the challenges in developing sustained-release local drug delivery systems is the limited treatment volume that can be achieved. In this work, we examine the effectiveness of using low frequency, high intensity ultrasound to promote the spatial penetration of drug molecules away from the implant/injection site boundary upon release from injectable, phase inverting poly(lactic acid-co-glycolic acid) (PLGA) implants. Fluorescein-loaded PLGA solutions were injected into poly(acrylamide) phantoms, and the constructs were treated daily for 14 days with ultrasound at 2.2 W/cm2 for 10 min. The 2D distribution of fluorescein within the phantoms was quantified using fluorescence imaging. Implants receiving ultrasound irradiation showed a 1.7-5.6 fold increase (p < 0.05) in fluorescence intensity and penetration distance, with the maximum increase observed 5 days post-implantation. However, this evidence was not seen when the same experiment was also carried out in phosphate buffer saline (pH 7.4). Results suggest an active role of ultrasound in local molecular transport in the phantom. An increase of fluorescein release and penetration depth in phantoms can be accomplished through brief application of ultrasound. This simple technique offers an opportunity to eventually enhance the therapeutic efficacy and broaden the application of local drug delivery systems.

Photo- and thermo-responsive multicompartment hydrogels for synergistic delivery of gemcitabine and doxorubicin.

Hydrogels have found promising applications in drug delivery due to their biocompatibility, high drug loading capability, and tunable release profiles. However, hydrogel-based carriers are primarily employed for delivering hydrophilic payloads while hydrophobic drugs cannot be efficiently delivered due to the lack of hydrophobic domains within conventional hydrogel matrices. Herein, we report that thermo- and photo-responsive hydrogels could be constructed from amphiphilic triblock copolymers, poly(N-isopropylacrylamide)-b-poly(4-acryloylmorpholine)-b-poly(2-((((2-nitrobenzyl)oxy)carbonyl) amino)ethyl methacrylate) (PNIPAM-b-PNAM-b-PNBOC), and the resulting hydrogels could be further engineered a new carrier for both hydrophilic gemcitabine (GCT) and hydrophobic doxorubicin (DOX). PNIPAM-b-PNAM-b-PNBOC triblock copolymers were first self-assembled into micelles with hydrophobic photosensitive PNBOC cores, hydrophilic PNAM inner shells, and thermoresponsive PNIPAM coronas below the lower critical solution temperature (LCST), while hydrogels of physically cross-linked micellar nanoparticles were achieved at elevated polymer concentrations and high temperatures above the critical gelation temperature (CGT). Rheological experiments revealed that the CGT was highly dependent on polymer compositions and concentrations, that is, a longer hydrophobic PNBOC block or a higher polymer concentration led to a decreased CGT. However, the CGT prior to UV irradiation (CGT0) could be drastically elevated after UV irradiation (CGTUV) as a result of UV irradiation-induced concurrently cross-linking and hydrophobic-to-hydrophilic transition within PNBOC cores. As such, gel-to-sol transition could be accomplished by either temperature decrease or exposure to UV irradiation at a fixed temperature lower than the CGTUV. Note that both GCT and DOX could be simultaneously encapsulated into the hydrogels due to the coexistence of extramicellar aqueous phase and hydrophobic micellar cores. Intriguingly, the subsequent co-release of GCT and DOX could be regulated by taking advantage of either temperature or UV irradiation-mediated gel-to-sol transitions.

Dual-function nanostructured lipid carriers to deliver IR780 for breast cancer treatment: Anti-metastatic and photothermal anti-tumor therapy.

Cancer treatments that use a combination of approaches with the ability to affect multiple disease pathways have proven highly effective. The present study reports on CXCR4-targeted nanostructured lipid carriers (NLCs) with a CXCR4 antagonist AMD3100 in the shell (AMD-NLCs). AMD-NLCs loaded with IR780 (IR780-AMD-NLCs) reduced the invasiveness of cancer cells, while simultaneously mediating efficient tumor targeting and photothermal therapeutic outcomes. We present the combined effect of encapsulated IR780 on photothermal therapy and of the AMD3100 coating on tumor targeting, CXCR4 antagonism and inhibition of cancer cell invasion and breast cancer lung metastasis in vitro and in vivo. IR780-AMD-NLCs exhibited excellent IR780 loading capacity and AMD3100 coating efficiency. The photothermal properties of IR780 were improved by encapsulation in NLCs. The encapsulated IR780 displayed better heat generating efficiency than free IR780 when exposed to repeated laser irradiation. CXCR4 antagonism and cell invasion assays confirmed that IR780-AMD-NLCs fully inhibited CXCR4 while IR780-NLCs did not function as CXCR4 antagonists. AMD3100-coated NLCs accumulated at high levels in tumors, as judged by in vivo imaging and biodistribution assays. Furthermore, CXCR4-targeted NLCs exhibited an encouraging photothermal anti-tumor effect as well as anti-metastatic efficacy in vivo. These findings suggest that this simple and stable CXCR4-targeted IR780 delivery system holds great promise for prevention of metastasis and for photothermal treatment of tumors. STATEMENT OF SIGNIFICANCE: Breast cancer is a major threat to human health, it is not the primary breast tumor that is ultimately responsible for the majority of deaths, but the tumor metastasis, which frequently follows a specific pattern of dissemination. We report development of a novel dual-function nanostructured lipid carrier (NLC) for breast cancer treatment. The carrier encapsulates NIR dye IR780 in its core and contains antagonist of the chemokine receptor CXCR4 in its shell. Our results show that by combining the CXCR4 antagonism with photothermal effect of the dye leads to remarkable antitumor and antimetastatic activity in syngeneic orthotopic model of metastatic breast cancer. Furthermore, the developed system also shows a theranostic potential due to NIR fluorescence of the encapsulated dye.

Two-photon absorption-controlled multidose drug release: a novel approach for secondary cataract treatment.

Tens of millions of cataract surgeries are done every year and the number is increasing heavily. Posterior capsule opacification is the major postoperative complication with an incidence of 10 to 50% within 5 years, depending on the age of the patient. We present a novel approach for secondary cataract treatment in a noninvasive manner. Photochemically triggered drug release from a polymer enables repeated drug applications for cataract treatment years after implantation of the intraocular lens, just when needed. However, light in the visible spectral range must pass through the lens but must not induce drug release. We demonstrate that two-photon absorption photochemistry is a powerful tool to overcome this problem. With wavelengths in the visible regime, a photochemical reaction that requires energies in the UV is triggered. The high intensities needed for this process never occur in any lighting condition in daily lives, but may be easily obtained with focused laser beams routinely used in ophthalmology. The properties of the therapeutic system are specified and the function is demonstrated by in-vitro cell tests. Noninvasive multidose photochemically triggered drug release from implanted intraocular lenses carrying a drug depot may be a therapeutic as well as an economic choice to established treatments of secondary cataracts.

Conducting polymers with defined micro- or nanostructures for drug delivery.

Conducting polymers (CPs) are redox active materials with tunable electronic and physical properties. The charge of the CP backbone can be manipulated through redox processes, with accompanied movement of ions into and out of the polymer to maintain electrostatic neutrality. CPs with defined micro- or nanostructures have greatly enhanced surface areas, compared to conventionally prepared CPs. The resulting high surface area interface between polymer and liquid media facilities ion exchange and can lead to larger and more rapid responses to redox cycling. CP systems are maturing as platforms for electrically tunable drug delivery. CPs with defined micro- or nanostructures offer the ability to increase the amount of drug that can be delivered whilst enabling systems to be finely tuned to control the extent and rate of drug release. In this review, fabrication approaches to achieve CPs with micro- or nanostructure are outlined followed by a detailed review and discussion of recent advances in the application of the materials for drug delivery.

Effect of High-Intensity Focused Ultrasound on Drug Release from Doxorubicin-Loaded PEGylated Liposomes and Therapeutic Effect in Colorectal Cancer Murine Models.

The goal of the study described here was to evaluate the use of high-intensity focused ultrasound (HIFU) in drug release and its application in cancer therapy. HIFU was set to minimize hyperthermia, particularly non-specific hyperthermia, of exposed areas. An in vitro temperature-sensitive hydrogel phantom model determined the parameters of HIFU under mild condition settings (spatial average temporal average intensity [ISATA] = 83.35 W/cm(2)). PEGylated liposomal indocyanine green (LCLP-ICG) and PEGylated liposomal doxorubicin (LCLP-Dox) were prepared with the same mole ratio to allow direct comparison of drug release in vitro and in vivo. We induced drug release with HIFU treatment using LCLP-ICG coupled with optical imaging in vitro and in vivo. The size distribution changes in LCLP-ICG in vitro and fluorescence intensity changes in ICG after intra-tumoral injection of LCLP-ICG into CT26 solid tumors in vivo followed by HIFU confirmed the feasibility of the system. We validated the therapeutic effect of HIFU treatment of the CT26 mouse tumor model. The tumor growth rate was significantly reduced (p < 0.05) only in the group administered LCLP-Dox followed by cycles of HIFU treatment, and the chemotherapy of the CT26 solid tumors was found to be highly efficient.

Radiation synthesis of interpolymer polyelectrolyte complex and its application as a carrier for colon-specific drug delivery system.

Novel pH-sensitive interpolymer polyelectrolyte complex was synthesized by gamma radiation-induced copolymerization of acrylic acid (AAc) and dimethyl aminoethyl methacrylate (DMAEMA). pH-dependent swelling showed different phase transitions depending on the copolymer composition and also showed the interpolymer polyelectrolyte complex formation at pH values ranged from pH 3 to pH 4. FT-IR and TGA was employed to study the complex formation. The influence of copolymer composition and pH value of the surrounding medium on the type of water diffusion in the glassy polymer was discussed. The ability of the prepared copolymer to be used as drug carrier for colon-specific drug delivery system was estimated using ketoprofen as a model drug.