Sustained Release Of Therapeutic Agents Research Articles

Highly Prolonged Release of the Cancer Vaccine and Immunomodulator via a Two-Layer Biodegradable Microneedle for Prophylactic Treatment of Metastatic Cancer.

Simultaneous sustained release of cancer vaccines and immunomodulators may effectively trigger durable immune responses and avoid multiple administrations. Here, we established a biodegradable microneedle (bMN) based on a biodegradable copolymer matrix made of polyethylene glycol (PEG) and poly(sulfamethazine ester urethane) (PSMEU). This bMN was applied to the skin and slowly degraded in the epidermis/dermis layers. Then, the complexes composed of a positively charged polymer (DA3), cancer DNA vaccine (pOVA), and toll-like receptor 3 agonist poly(I/C) were synchronously released from the matrix in a pain-free manner. The whole microneedle patch was fabricated with two layers. The basal layer was formed using polyvinyl pyrrolidone/polyvinyl alcohol that could be rapidly dissolved upon applying the microneedle patch to the skin, whereas the microneedle layer was formed by complexes encapsulating biodegradable PEG-PSMEU, which was stuck at the injection site for sustained release of therapeutic agents. According to the results, 10 days is the time for the complexes to be completely released and express specific antigens in antigen-presenting cells in vitro and in vivo. It is noteworthy that this system could successfully elicit cancer-specific humoral immune responses and inhibit metastatic tumors in the lungs after a single shot of immunization.

Advances in Xanthan Gum-Based Systems for the Delivery of Therapeutic Agents

In the last three decades, polymers have contributed significantly to the improvement of drug delivery technologies by enabling the controlled and sustained release of therapeutic agents, versatility in designing different delivery systems, and feasibility of encapsulation of both hydrophobic and hydrophilic molecules. Both natural and synthetic polymers have been explored for the delivery of various therapeutic agents. However, due to the disadvantages of synthetic polymers, such as lack of intrinsic biocompatibility and bioactivity, hydrophobicity, and expensive and complex procedure of synthesis, there is a move toward the use of naturally occurring polymers. The biopolymers are generally derived from either plants or microorganisms and have shown a wide range of applications in drug administration due to their hydrophilic nature, biodegradability, biocompatibility, no or low toxicity, abundance, and readily available, ease of chemical modification, etc. This review describes the applications of a biopolymer, xanthan gum (XG), in the delivery of various therapeutic agents such as drugs, genetic materials, proteins, and peptides. XG is a high molecular weight, microbial heteropolysaccharide and is produced as a fermented product of Gram-negative bacteria, Xanthomonas campestris. Traditionally, it has been used as a thickener in liquid formulations and an emulsion stabiliser. XG has several favourable properties for designing various forms of drug delivery systems. Furthermore, the structure of XG can be easily modified using different temperature and pH conditions. Therefore, XG and its derivatives have been explored for various applications in the food, pharmaceutical, and cosmetic industries.

Preparation of anisotropic multiscale micro-hydrogels via two-photon continuous flow lithography

HypothesisPolymeric anisotropic soft microparticles show interesting behavior in biological environments and hold promise for drug delivery and biomedical applications. However, self-assembly and substrate-based lithographic techniques are limited by low resolution, batch operation or specific particle geometry and deformability. Two-photon polymerization in microfluidic channels may offer the required resolution to continuously fabricate anisotropic micro-hydrogels in sub-10 µm size-range. ExperimentsHere, a pulsed laser source is used to perform two-photon polymerization under microfluidic flow of a poly(ethylene glycol) diacrylate (PEGDA) solution with the objective of realizing anisotropic micro-hydrogels carrying payloads of various nature, including small molecules and nanoparticles. The fabrication process is described via a reactive-convective-diffusion system of equations, whose solution under proper auxiliary conditions is used to corroborate the experimental observations and sample the configuration space. FindingsBy tuning the flow velocity, exposure time and pre-polymer composition, anisotropic PEGDA micro-hydrogels are obtained in the 1–10 μm size-range and exhibit an aspect ratio varying from 1 to 5. Furthermore, 200 nm curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and 100 nm ssRNA-encapsulating lipid nanoparticles were entrapped within square PEGDA micro-hydrogels. The proposed approach could support the fabrication of micro-hydrogels of well-defined morphology, stiffness, and surface properties for the sustained release of therapeutic agents.

An Investigation of the Interaction between Bovine Serum Albumin-Conjugated Silver Nanoparticles and the Hydrogel in Hydrogel Nanocomposites.

Nanocomposite hydrogels are attracting significant interest due to their potential use in drug delivery systems and tissue scaffolds. Stimuli-responsive hydrogel nanocomposites are of particular interest due to sustained release of therapeutic agents from the hydrogel. However, challenges such as controlled release of therapeutic agents exist because of limited understanding of the interactions between the therapeutic agent and the hydrogel. To investigate the interaction, we synthesize a hydrogel nanocomposite by crosslinking the hydrogel precursors (tetrazine-modified polyethylene glycol and norbornene-modified hyaluronic acid) using click chemistry while bovine serum albumin-capped silver nanoparticles were encapsulated in situ in the matrix. The interaction between the nanoparticles and the hydrogel was studied by a combination of spectroscopic techniques. X-ray photoelectron spectroscopy results suggest that the hydrogel molecule rearranges so that polyethylene glycol is pointing up toward the surface while hyaluronic acid folds to interact with bovine serum albumin of the nanoparticles. Hyaluronic acid, facing inward, may interact with the nanoparticle via hydrogen bonding. The hydrogel nanocomposite showed antibacterial activity against Gram-positive/Gram-negative bactericides, supporting time-based nanoparticle release results. Our findings about interactions between the nanoparticles and the hydrogel can be useful in the formulation of next generation of hydrogel nanocomposites.

Mesenchymal Stem Cells: A New Generation of Therapeutic Agents as Vehicles in Gene Therapy.

In recent years, mesenchymal stem cells (MSCs) as a new tool for therapeutic gene delivery in clinics have attracted much attention. Their advantages cover longer lifespan, better isolation, and higher transfection efficiency and proliferation rate. MSCs are the preferred approach for cell-based therapies because of their in vitro self-renewal capacity, migrating especially to tumor tissues, as well as anti-inflammatory and immunomodulatory properties. Therefore, they have considerable efficiency in genetic engineering for future clinical applications in cancer gene therapy and other diseases. For improving therapeutic efficiency, targeted therapy of cancers can be achieved through the sustained release of therapeutic agents and functional gene expression induction to the intended tissues. The development of a new vector in gene therapy can improve the durability of a transgene expression. Also, the safety of the vector, if administered systemically, may resolve several problems, such as durability of expression and the host immune response. Currently, MSCs are prominent candidates as cell vehicles for both preclinical and clinical trials due to the secretion of therapeutic agents in several cancers. In the present study, we discuss the status of gene therapy in both viral and non-viral vectors along with their limitations. Throughout this study, the use of several nano-carriers for gene therapy is also investigated. Finally, we critically discuss the promising advantages of MSCs in targeted gene delivery, tumor inhibition and their utilization as the gene carriers in clinical situations.

Engineering and evaluation of forcespun functionalized carbon nano-onions reinforced poly (ε-caprolactone) composite nanofibers for pH-responsive drug release.

Nanofibers and smart polymers are potentially fascinating biomaterials for the sustained release of therapeutic agents and tissue engineering applications. The current study describes a new class of pH-controlled polycaprolactone/mercaptophenyl methacrylate functionalized carbon nano-onions (PCL/f-CNOs) composite nanofibers by Forcespinning® (FS) with a sustained drug release profile. The morphology and structural characteristics of PCL/f-CNOs nanofibers were scrutinized by Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), respectively. The morphological results revealed that FS provided homogeneous and bead free nanofibers with average diameters from approximately 215nm to 596nm. PCL/f-CNOs composite fibers exhibited pH-responsive release of DOX over 15days; pH6.5 showed 87%, and pH5.0 presented around 99% of DOX release. Drug release measurements showed that the π-π stacking interactions between DOX and f-CNOs have led to a controlled DOX release from forcespun PCL/f-CNOs fibers. Owing to the f-CNOs amalgamation, PCL/f-CNOs fibers unveiled enhanced tensile strength (3.16MPa) as compared to pristine PCL fibers. It reveals the magnitude of colloidal stability and physisorption of f-CNOs within the PCL matrix. Besides, the in-vitro cell viability was measured with human fibroblast cells, and good viability was observed. Nevertheless, DOX embedded pH-responsive PCL/f-CNOs composite nanofibers may show potential applications in the biomedical research area.

Dual drug loaded PLGA nanospheres for synergistic efficacy in breast cancer therapy

Improved therapeutic effects can be achieved by the delivery of combination of drugs through multifunctional cell targeted nanocarrier systems. The present investigation reports the preparation of Poly (D,L-lactic-co-glycolic acid) (PLGA) nanospheres loaded with the novel combination such as Rutin (R) and Benzamide (B) as drugs using water-oil-water (w/o/w) emulsion method. Dual drug loaded PLGA nanospheres (R/B@PLGA) were stabilized by poly (vinyl alcohol) (PVA) coating and characterized in terms of morphology, size, surface charge, and structural chemistry by Scanning electron microscopy (SEM), Dynamic light scattering (DLS), Zeta potential analysis, UV–vis and Fourier transform infrared (FT-IR) spectroscopy. The inhibitory effects of rutin and benzamide on MDA-MB-231 (triple negative breast cancer-TNBC) cells using the drug loaded PLGA nanospheres as well as their non-toxic features were evaluated in vivo. The anticancer activity of the R/B@PLGA nanospheres through cell cycle disruption and apoptotic induction was assessed in vitro by flow cytometry analysis. Further, the in vitro antioxidant capacity, pH-based drug release and hemocompatible property were also investigated. It was shown that the R/B@PLGA nanospheres lacked genotoxic potential and they did not alter the antioxidant enzyme activities and histological features of zebrafish. Hence, this dual drug delivery system (DDS) not only actively targets multidrug-resistance (MDR) associated phenotype but also improves the therapeutic efficiency by its non-toxic nature towards enhanced cancer cell focused delivery and sustained release of therapeutic agents.

A collagen microchannel scaffold carrying paclitaxel-liposomes induces neuronal differentiation of neural stem cells through Wnt/β-catenin signaling for spinal cord injury repair

Neural stem cells (NSCs) show potential for spinal cord injury (SCI) repair. However, the current challenge is to direct their differentiation into neurons in the lesion site. It has been demonstrated that transplanted NSCs primarily differentiated into astrocytes rather than neurons due to the adverse microenvironment. It was reported that microtubule-stabilizing agent paclitaxel (PTX) was able to reduce scarring and enhance intrinsic axon regeneration after SCI. In this study, the effect of PTX on NSC differentiation was studied. It was demonstrated for the first time that PTX could rescue myelin-inhibited neuronal differentiation of NSCs, and induced a higher neuronal differentiation as compared with that in normal microenvironment. Enhanced neuronal differentiation in normal microenvironment further validated that PTX was capable of inducing intrinsic neuronal differentiation of NSCs. Furthermore, a functional collagen scaffold was developed by loading PTX-encapsulated liposomes into a collagen microchannel scaffold, leading to a prolonged sustained release of PTX. When NSC-laden functional collagen scaffold was implanted into T8 complete transection site of rat spinal cord, the scaffold provided an instructive microenvironment for neuronal differentiation of NSCs, motor and sensory neuron regeneration, and axon extension. The neural regeneration eventually led to improvement in motor evoked potential and hindlimb locomotion recovery. Moreover, mRNA-Seq and western blotting results revealed that PTX-triggered neuronal differentiation occurred through Wnt/β-catenin signaling pathway. Together, the collagen microchannel scaffold in combination with sustained release of therapeutic agents for inducing neuronal differentiation of NSCs is promising for SCI repair.

Hierarchical Microplates as Drug Depots with Controlled Geometry, Rigidity, and Therapeutic Efficacy.

A variety of microparticles have been proposed for the sustained and localized delivery of drugs with the objective of increasing therapeutic indexes by circumventing filtering organs and biological barriers. Yet, the geometrical, mechanical, and therapeutic properties of such microparticles cannot be simultaneously and independently tailored during the fabrication process to optimize their performance. In this work, a top-down approach is employed to realize micron-sized polymeric particles, called microplates (μPLs), for the sustained release of therapeutic agents. μPLs are square hydrogel particles, with an edge length of 20 μm and a height of 5 μm, made out of poly(lactic- co-glycolic acid) (PLGA). During the synthesis process, the μPL Young's modulus can be varied from 0.6 to 5 MPa by changing the PLGA amounts from 1 to 7.5 mg, without affecting the μPL geometry while matching the properties of the surrounding tissue. Within the porous μPL matrix, different classes of therapeutic payloads can be incorporated including molecular agents, such as anti-inflammatory dexamethasone (DEX), and nanoparticles containing imaging and therapeutic molecules themselves, thus originating a truly hierarchical platform. As a proof of principle, μPLs are loaded with free DEX and 200 nm spherical polymeric nanoparticles, carrying DEX molecules (DEX-SPNs). Electron and fluorescent confocal microscopy analyses document the uniform distribution and stability of molecular and nanoagents within the μPL matrix. This multiscale, hierarchical microparticle releases DEX for at least 10 days. The inclusion of DEX-SPNs serves to minimize the initial burst release and modulate the diffusion of DEX molecules out of the μPL matrix. The biopharmacological and therapeutic properties together with the fine tuning of geometry and mechanical stiffness make μPLs a unique polymeric depot for the potential treatment of cancer, cardiovascular, and chronic, inflammatory diseases.

Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy: in vitro and in vivo evaluations

Sustained release of therapeutic agents into tumor cells is a potential approach to improve therapeutic efficacy, decrease side effects, and the drug administration frequency. Herein, we used the modified double-emulsion solvent evaporation (DSE) method to prepare a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS). The prepared rough PTX-PLGA-MS possessed microporous surface and highly porous internal structures, which significantly influenced the drug entrapment and release behaviors. The rough MS with an average particle size of 53.47 ± 2.87 μm achieved high drug loading (15.63%) and encapsulation efficiency (92.82%), and provided a favorable sustained drug release. The in vitro antitumor tests of flow cytometry and fluoroimmunoassay revealed that the rough PTX-PLGA-MS displayed effective anti-gliomas activity and enhanced the cellular PTX uptake through adsorptive endocytosis. Both in vitro and in vivo antitumor results demonstrated that the sustained-release PTX could induce the microtubules assembly and the over-expression of Bax and Cyclin B1 proteins, resulting in the microtubule dynamics disruption, G2/M phase arrest, and cell apoptosis accordingly. Furthermore, as the rough PTX-PLGA-MS could disperse and adhere throughout the tumor sites and cause extensive tumor cell apoptosis with one therapeutic course (12 days), they could reduce the system toxicity and drug administration frequency, thus achieving significant tumor inhibitory effects with rapid sustained drug release. In conclusion, our results verified that the rough PTX-PLGA-MS drug release system could serve as a promising treatment to malignant glioma.

Injectable hydrogels for sustained release of therapeutic agents

Hydrogels are natural or synthetic polymer networks that exhibit high water absorbent capacities and have been used as scaffolds for tissue engineering or as delivery carriers for therapeutic agents and cells. Owing to their tunable physicochemical properties, hydrogels can provide spatial and temporal control over the release of loaded therapeutic agents, including chemotherapeutic drugs, proteins or cells. In particular, in situ-forming injectable hydrogels, the state-of-the-art clear free flowing polymer solutions that transform to viscoelastic gels upon exposure to stimuli including pH, temperature, light, enzymes and magnetic field, have been widely studied as delivery carriers for therapeutic agents. Therapeutic agents can be easily mixed with the free flowing polymer solutions and injected into the subcutaneous tissue or target site that could form a viscoelastic gel and act as therapeutic agents release depot. Hence, injectable hydrogels paid attention as sustained delivery vehicles. In this review, we systematically summarize the development of biocompatible, biodegradable, and pH- and temperature-responsive injectable hydrogels for sustained release of therapeutic agents. The key factors responsible for in situ gelation, interaction between polymers and therapeutic agents, and controlling the degradation of hydrogel matrix, are discussed. Advantages and perspectives of pH- and temperature-responsive injectable hydrogels in sustained therapeutic agents release are highlighted.

Bone and metal targeted polymeric nanoparticles (US20150125391 A1): a patent evaluation

ABSTRACTIntroduction: Delivery of therapeutic agents to bone is crucial for the treatment of bone metastasis and other bone diseases. The present invention patent relates to bone- and metal-targeted polymeric nanoparticles for targeting delivery of therapeutic molecules to the pathological tissues in bone or the surgical metal implant-bone tissue interface.Areas covered: The nanoparticles for drug delivery were fabricated via the assembly of amphiphilic polymers, in which the hydrophilic outer layer was minimal to prolong the circulation time, and the hydrophobic insider core was biodegradable and loaded with therapeutic agents. Bone-targeted elements were conjugated on the nanoparticle surface to enhance their affinity to bone and/or metal implant surface.Expert opinion: A prolonged, sustained release of therapeutic agents was observed by using the delivery system targeting to bone. The described invention provides a bone-targeted vector to deliver diverse therapeutic agents to bone.

Biomedical Imaging in Implantable Drug Delivery Systems.

Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant- body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS.

Feasibility of localized immunosuppression: 3. Preliminary evaluation of organosilicone constructs designed for sustained drug release in a cell transplant environment using dexamethasone.

As part of our ongoing effort to develop biohybrid devices for pancreatic islet transplantation, we are interested in establishing the feasibility of a localized immune-suppressive approach to avoid or minimize the undesirable side effects of existing systemic treatments. Since biohybrid devices can also incorporate biocompatible scaffold constructs to provide a support environment for the transplanted cells that enhances their engraftment and long-term function, we are particularly interested in an approach that would use the same three-dimensional construct, or part of the same construct, to also provide sustained release of therapeutic agents to modulate the inflammatory and immune responses locally. Within this framework, here, we report preliminary results obtained during the investigation of the suitability of organosilicone constructs for providing sustained localized drug release using small, matrix-type polydimethylsiloxane (PDMS) disks and dexamethasone as a model hydrophobic drug. Following a short burst, long-term steady sustained release was observed under in vitro conditions at levels of 0.1-0.5 microg/day/disk with a profile in excellent agreement with that predicted by the Higuchi equation. To verify that therapeutic levels can be achieved, suppression of LPS-induced activation has been shown in THP-1 cells with disks that have been pre-soaked for up to 28 days. These preliminary results prove the feasibility of this approach where an integral part of the biomaterial construct used to enhance cell engraftment and long-term function also serves to provide sustained local drug release.

Multifunctional HER2-antibody conjugated polymeric nanocarrier-based drug delivery system for multi-drug-resistant breast cancer therapy.

Nanotechnology-based medical approaches have made tremendous potential for enhancing the treatment efficacy with minimal doses of chemotherapeutic drugs against cancer. In this study, using tamoxifen (Tam), biodegradable antibody conjugated polymeric nanoparticles (NPs) was developed to achieve targeted delivery as well as sustained release of the drug against breast cancer cells. Poly(D,L-lactic-co-glycolic acid) (PLGA) NPs were stabilized by coating with poly(vinyl alcohol) (PVA), and copolymer polyvinyl-pyrrolidone (PVP) was used to conjugate herceptin (antibody) with PLGA NPs for promoting the site-specific intracellular delivery of Tam against HER2 receptor overexpressed breast cancer (MCF-7) cells. The Tam-loaded PVP-PLGA NPs and herceptin-conjugated Tam-loaded PVP-PLGA NPs were characterized in terms of morphology, size, surface charge, and structural chemistry by dynamic light scattering (DLS), Transmission electron microscopy (TEM), ζ potential analysis, 1H nuclear magnetic resonance (NMR), and Fourier transform infrared (FT-IR) spectroscopy. pH-based drug release property and the anticancer activity (in vitro and in vivo models) of the herceptin conjugated polymeric NPs were evaluated by flow cytometry and confocal image analysis. Besides, the extent of cellular uptake of drug via HER2 receptor-mediated endocytosis by herceptin-conjugated Tam-loaded PVP-PLGA NPs was examined. Furthermore, the possible signaling pathway of apoptotic induction in MCF-7 cells was explored by Western blotting, and it was demonstrated that drug-loaded PLGA NPs were capable of inducing apoptosis in a caspase-dependent manner. Hence, this nanocarrier drug delivery system (DDS) not only actively targets a multidrug-resistance (MDR) associated phenotype (HER2 receptor overexpression) but also improves therapeutic efficiency by enhancing the cancer cell targeted delivery and sustained release of therapeutic agents.

Mussel Inspired Coating of a Biocompatible Cyclodextrin Based Polymer onto CoCr Vascular Stents

During the past decade, drug-eluting stents (DES) have been widely used for the treatment of occlusive coronary artery diseases. They are supposed to reduce the incidence of early in-stent restenosis by the elution of highly hydrophobic antiproliferative drugs. Nevertheless, the absence of long-term activity of these devices is responsible for late acute thrombosis probably due to the delayed re-endothelialization of the arterial wall over the bare metallic stent struts. Thus, a new generation of DES with a sustained release of therapeutic agents is required to improve long-term results of these devices. In this article, we report an original functionalization of CoCr vascular devices with a hydrophilic, biocompatible and biodegradable cyclodextrins based polymer which acts as a reservoir for lipophilic drugs allowing the sustained release of antiproliferative drugs. In this setting, polydopamine (PDA), a strong adhesive biopolymer, was applied as a first coating layer onto the surface of the metallic CoCr device in order to promote the strong anchorage of a cyclodextrin polymer. This polymer was generated "in situ" from the methylated cyclodextrins and citric acid as a cross-linking agent through a polycondensation reaction. After optimization of the grafting process, the amount of cyclodextrin polymer coated onto the CoCr device was quantified by colorimetric titrations and the resulting film was characterized by scanning electron microscopy (SEM) investigations. The cytocompatibility of the resulting coated film was assessed by cell proliferation and vitality tests. Finally, the ability of this coated device to act as a drug-eluting system was evaluated with paclitaxel, a strong hydrophobic antiproliferative drug, a reference drug used in current vascular drug-eluting stents.

Modifications of Chitosan for Use in Nanoparticulate Drug Delivery Systems

Nanoparticles with naturally occurring biodegradable polymers have emerged as potential carriers of various therapeutic agents. Chitosan, a cationic polysaccharide, is one of such biodegradable polymers, which has been extensively exploited for the preparation of nanoparticles with several therapeutic agents. In recent years, the area of focus has shifted from chitosan to chitosan derivatized polymers due to its vastly improved properties such as better drug retention capability, improved permeation, enhanced mucoadhesion, and sustained release of therapeutic agents. Chitosan derivatized polymers are primarily the quaternized chitosan derivatives, chitosan cyclodextrin complexes, thiolated chitosan, pegylated chitosan, chitosan combined with sugar ligands, chitosan with cholanic acid, chitosan-linolenic acid and chitosan-DTPA. This review article covers the various modifications of chitosan, their preparation procedures and various works done with them. 

Sustained delivery of hydrocortisone acetate by CS/N-vinyl-2-pyrrolidone/CaCO3 microparticle hybrid hydrogels

The goal of this research is to develop a composite hydrogel system for sustained release of therapeutic agents. The hybrid hydrogels were prepared by radiation crosslinking on aqueous solution of Chitosan (CS)/N-vinyl-2-pyrrolidone (NVP) with different loads of CaCO3 in the presence of hydrocortisone acetate (HCA), an anti-inflammatory drugs. Physical characteristics of CS/NVP/CaCO3 were studied using X-ray diffraction (XRD) and infrared spectrophotometery (IR). The porous structure of resulted hydrogel was confirmed by SEM micrographs. The effect of doses and calcium carbonate amount on the swelling of the hydrogels was investigated. The ability of the prepared CS/NVP/CaCO3-based hybrid hydrogels to be used as drug carriers for anti-inflammatory-specific drug delivery system was estimated using HCA as a model drug. POLYM. COMPOS., 35:1176–1183, 2014. © 2013 Society of Plastics Engineers

The inhibition of tumor growth and metastasis by self-assembled nanofibers of taxol

Molecular hydrogels have big potential for local delivery and sustained release of therapeutic agents. In this paper, we reported on a molecular hydrogel mainly formed by the widely used anti-cancer drug of taxol. The hydrogel was formed by an ester bond hydrolysis process from a taxol derivative (Taxol-SA-GSSG, 1) and could be administrated into solid tumors to dramatically hinder their growths and prevent their metastasis. Besides the improved anti-cancer effect compared to the clinically used intravenous (i.v.) injection of Taxol®, the concentration of taxol in blood was low due to the local administration of taxol hydrogels, which greatly enhanced the dosage tolerance of mice to taxol and might reduce side effects of taxol during chemotherapy. Our observations suggested that the hydrogel mainly composed of taxol would have great potential for its practical applications.

Drug Release from a pH-Sensitive Multiblock Co-Polymer Thermogel

A Pluronic®-based pH-sensitive multiblock co-polymer thermogel has been proposed for sustained release of therapeutic agents. Hydrophobic small-molecule drugs (paclitaxel and camptothecin) and model hy-drophilic macromolecules (fluorescein-labeled dextrans of molecular mass 10, 20, 40, 150 and 250 kDa) were successfully loaded into and released from the thermogels. Drug-loaded polymer solutions were characterized for gelation behavior and micelle size. Drug loading increased the size of the multiblock co-polymer micelles from 20 to 100 nm. The co-polymer improved paclitaxel and camptothecin loading in an aqueous solution by 6900- and 1050-fold, respectively, compared to their solubility in water. The ther-mogels released loaded drugs in a pH-dependent fashion, regardless of their properties. At pH 5.0 and 6.5, paclitaxel and camptothecin completely released in 4 and 15 days, respectively, by a combined mechanism of diffusion and erosion. At neutral pH, diffusion predominated gel erosion to sustain the drug release up to 40 days. Fluorescein-labeled dextran release from the thermogels showed a similar pH-dependent trend as the hydrophobic small molecule drugs. However, dextran release at neutral pH was entirely dependent on the molecular mass of the dextran. Low-molecular-mass (10 and 20 kDa) dextrans were completely released in 12 and 21 days, respectively, while high-molecular-mass (⩾40 kDa) dextrans being continuously released over 36 days, indicating that the threshold of molecular weight necessary for sustained release of a hydrophilic macromolecule from this thermogel (e.g., enzymes, monoclonal antibodies and immunotoxins) is 40 kDa. Taken together, the MBCP thermogel showed potential as a controlled drug-delivery system that showed sustained release of both hydrophilic and lipophilic molecules.