pH-sensitive Release Research Articles

A biocompatible theranostic nanoplatform based on magnetic gadolinium-chelated polycyclodextrin: in vitro and in vivo studies

A novel theranostic nanoplatform was prepared based on Fe3O4 nanoparticles (NPs) coated with gadolinium ions decorated-polycyclodextrin (PCD) layer (Fe3O4@PCD-Gd) and employed for Curcumin (CUR) loading. The dissolution profile of CUR indicated a pH sensitive release manner. Fe3O4@PCD-Gd NPs exhibited no significant toxicity against both normal and cancerous cell lines (MCF 10A and 4T1, respectively); while the CUR-free NPs showed more toxicity against 4T1 than MCF 10A cells. In vivo anticancer study revealed appropriate capability of the system in tumor shrinking with no tissue toxicity and adverse effect on body weight. In vivo MR imaging of BALB/c mouse showed both T1 and T2 contrast enhancement on the tumor cells. Fe3O4@PCD-Gd/CUR NPs showed significant features as a promising multifunctional system having appropriate T1-T2 dual contrast enhancement and therapeutic efficacy in cancer theranostics.

Design and characterization of a novel pH-sensitive biocompatible and multifunctional nanocarrier for in vitro paclitaxel release

Breast cancer is one of the main reasons of women's mortality. A novel ternary combination of ZnAl-layered double hydroxides (LDH), cobalt ferrite (CoFe2O4) and N-graphene quantum dots (N-GQDs) proposes a pH-sensitive multifunctional nanocomposite that can improve therapeutic features of each compound; this is a notable strategy to make biocompatible materials with unique properties for paclitaxel (PTX) delivery in breast cancer cells. For proving the surface modification process of materials, electrochemical techniques including cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were carried out. By coating PEG on the surface of the N-GQDs/CoFe2O4/LDH, it developed a drug delivery system with low toxicity, an excellent encapsulation efficiency 88.4%, drug loading capacity of ca. 31%, and slow and sustained release behavior (9% after 72 h) under normal physiological conditions. Besides, a high drug release (~69%) at low-pH as a model of the extracellular tumor environment indicated a pH-sensitive release behavior. Moreover, cell viability assay proved the negligible cytotoxicity on normal cells (L929) and the improved growth inhibition effect of PTX/N-GQDs/CoFe2O4/LDH nanocarrier on MCF7 cancer cells. Blood compatibility test values with respect to red blood cell aggregation (RBC), coagulation prothrombin time (PT), activated partial thromboplastin time (APTT), and complement activation (C3 and C4 levels) remained within normal ranges without toxicity effect on RBCs and complement factors. Overall, this novel designed PTX/N-GQDs/CoFe2O4/LDH nanocarrier with tremendously biocompatible, slow-release and pH-dependent features could be considered as a theranostic candidate for various anticancer drugs delivery and cancer therapy.

Tryptophan-functionalized graphene quantum dots with enhanced curcumin loading capacity and pH-sensitive release

Tryptophan-conjugated graphene quantum dots (Trp-GQDs) were fabricated for the first time and loaded with curcumin (Cur) as a hydrophobic anticancer agent, to evaluate Cur loading capacity and release kinetics, as well as its cytotoxicity effect on human breast cancer cells. The GQDs were synthesized through a facile oxidation method, Trp was conjugated onto GQDs via amide bonds and Cur was loaded onto GQDs and Trp-GQDs by non-covalent interactions. TEM, FESEM, PL, UV–Vis, and FTIR analysis were used to study the nano-assemblies structural and spectral characterizations. The drug loading capacity increased by increasing the initial concentration of Cur, and by 23% after the conjugation of GQDs with Trp. A pH-sensitive release was also detected at pH 5.5 and 7.4. Moreover, the experimental release data of Cur from the two nano-assemblies at both pHs had the best compliance with the pseudo-second-order model. In-vitro cellular cytotoxicity on MCF-7 cells demonstrated the nontoxicity of the bare GQDs and Trp-GQDs nanocarriers. Considering the biocompatibility, traceability, high drug loading capacity, and pH-sensitivity of Trp-GQDs nanocarrier, it can be concluded that Cur/Trp-GQDs can be regarded as a promising candidate for drug delivery applications.

Polydopamine-Modified Metal-Organic Frameworks, NH2-Fe-MIL-101, as pH-Sensitive Nanocarriers for Controlled Pesticide Release.

Recently, metal–organic frameworks (MOFs) have become a dazzling star among porous materials used in many fields. Considering their intriguing features, MOFs have great prospects for application in the field of sustainable agriculture, especially as versatile pesticide-delivery vehicles. However, the study of MOF-based platforms for controlled pesticide release has just begun. Controlled pesticide release responsive to environmental stimuli is highly desirable for decreased agrochemical input, improved control efficacy and diminished adverse effects. In this work, simple, octahedral, iron-based MOFs (NH2-Fe-MIL-101) were synthesized through a microwave-assisted solvothermal method using Fe3+ as the node and 2-aminoterephthalic acid as the organic ligand. Diniconazole (Dini), as a model fungicide, was loaded into NH2-Fe-MIL-101 to afford Dini@NH2-Fe-MIL-101 with a satisfactory loading content of 28.1%. The subsequent polydopamine (PDA) modification could endow Dini with pH-sensitive release patterns. The release of Dini from PDA@Dini@NH2-Fe-MIL-101 was much faster in an acidic medium compared to that in neutral and basic media. Moreover, Dini@NH2-Fe-MIL-101 and PDA@Dini@NH2-Fe-MIL-101 displayed good bioactivities against the pathogenic fungus causing wheat head scab (Fusarium graminearum). This research sought to reveal the feasibility of versatile MOFs as a pesticide-delivery platform in sustainable crop protection.

Study of pH-Responsive and Polyethylene Glycol-Modified Doxorubicin-Loaded Mesoporous Silica Nanoparticles for Drug Delivery.

Tumor-targeted drug delivery systems represent challenging and widely investigated strategies to enhance cancer chemotherapy. In this study, we introduce a novel high-hydrophilic mesoporous silica nanoparticle system with a pH-sensitive drug release. The resultant composite nanoparticles appear as spheres of uniform size (450±25 nm) with a porous structure, which enables a high drug-loading ratio. Through modification of chitosan and polyethylene glycol monomethyl ether, the modified mesoporous silica was non-toxic to normal cells, but effective at inducing tumor cell death. With regard to the characteristics of drug release, the modified mesoporous silica clearly displayed a pH-stimulated release of the model drug doxorubicin hydrochloride in an acidic phosphate buffer solution (pH 4.0 and 6.0). The release was much greater than that observed in neutral or alkaline phosphate buffer solutions (pH 7.3 and 8.0). Furthermore, the release behavior was in accordance with the Higuchi model, indicating that this modified mesoporous silica drug delivery system can exhibit controlled release. The above results imply that the modified mesoporous silica is an effective drug delivery system for cancer therapy.

An innovative wax-based enteric coating for pharmaceutical and nutraceutical oral products.

In this work, a novel enteric coating based on natural waxes and alginate was reported. Initially, theophylline tablets were coated with emulsified ceresin wax in heated aqueous alginate solution using a fluidised bed coating technology. A coating level of 10% proved sufficient to prevent tablets from uptaking gastric medium (<5%) and produced a delayed release profile that complies to the pharmacopeial criteria of enteric coating release. Then, a wide range of emulsions based on other natural waxes (white beeswax, yellow beeswax, cetyl palmitate, carnauba wax or rice bran wax) yielded coatings with similar disintegration times and release profiles. Interestingly, the ceresin-based coating showed a superior performance at inhibiting acid uptake and enabling highly pH-responsive drug release in comparison to different commercially available GRAS enteric coating products (Eudraguard® Control, Swanlac® ASL10, and Aquateric™ N100). The coating was stable for 6months at 30°C and 65% RH. This innovative approach of applying hot O/W emulsion of natural waxes yielded an aesthetically attractive and stable coating with gastric protection and pH-sensitive release properties. The novel coating can be an efficient and promising alternative to overcome the shortcomings of current GRAS grade enteric coating products.

A biocompatible glycol-capped nano-delivery system with stimuli-responsive drug release kinetics abrogates cancer cell survival

An eco-friendly polysaccharide (PSP001) isolated from the fruit rind of Punica granatum is a biodegradable polymer with immunostimulatory and anticancer properties. PSP001 was employed for the stimuli-responsive targeted delivery of antineoplastic agent doxorubicin (Dox) by the fabrication of Dox-holding PSP nanoparticles (DPN). The galactose moieties of PSP001 were occupied as an effective tumor-targeted motif against the over-expressed asialoglycoprotein and galectin receptors of cancers. DPN followed a pH-sensitive cargo release kinetics, competent cancer cell internalization profile, and appealing biocompatibility towards peripheral red blood cells. The selective execution of caspase-mediated programmed cell death by the DPN on cancer cells was confirmed with multiple apoptosis studies. Extensive toxicity profiling on BALB/c mice rules out any palpable signs of abnormality with DPN administration while bare Dox produced vital signs of toxicity. Studies on syngraft solid tumor-bearing mice uncovered the tumor homing nature of DPN with the subsequent release of the entrapped drug which further translated in the direction of a significant reduction in the tumor payload and enhanced survival benefits, thus offering a robust approach towards endurable cancer management.

Inhalable solid lipid nanoparticles for intracellular tuberculosis infection therapy: macrophage-targeting and pH-sensitive properties.

Mycobacterium tuberculosis (MTB) is one of the most threatening pathogens for its latent infection in macrophages. The intracellular MTB isolated itself from drugs and could spread via macrophages. Therefore, a mannose-modified macrophage-targeting solid lipid nanoparticle, MAN-IC-SLN, loading the pH-sensitive prodrug of isoniazid (INH), was designed to treat the latent tuberculosis infection. The surface of SLNs was modified by a synthesized 6-octadecylimino-hexane-1,2,3,4,5-pentanol (MAN-SA) to target macrophages, and the modified SLNs showed a higher cell uptake in macrophages (97.2%) than unmodified SLNs (42.4%). The prodrug, isonicotinic acid octylidene-hydrazide (INH-CHO), was synthesized to achieve the pH-sensitive release of INH in macrophages. The INH-CHO-loaded SLNs exhibited a pH-sensitive release profile and accomplished a higher accumulated release in pH5.5 media (82.63 ± 2.12%) compared with the release in pH7.4 media (58.83 ± 3.84%). Mycobacterium smegmatis was used as a substitute for MTB, and the MAN-IC-SLNs showed a fourfold increase of intracellular antibiotic efficacy and enhanced macrophage uptake because of the pH-sensitive degradation of INH-CHO and MAN-SA in SLNs, respectively. For the in vivo antibiotic efficacy test, the SLNs group displayed an 83% decrease of the colony-forming unit while the free INH group only showed a 60% decrease. The study demonstrates that macrophage targeting and pH-sensitive SLNs can be used as a promising platform for the latent tuberculosis infection. Graphical Abstract Table of contents: Macrophage-targeting and pH-sensitive solid lipid nanoparticles (SLN) were administrated to the lung via nebulization. Macrophage targeting was achieved by appropriate particle size and surface mannose modification with synthesized MAN-SA. After being swallowed by macrophages, the prodrug, Isonicotinic acid octylidene-hydrazide (INH-CHO), quickly released isoniazid, which was triggered by the intracellular acid environment. The SLNs exhibited higher intracellular antibiotic efficacy due to their macrophage-targeting and pH-sensitive properties.

Colitis-targeted hybrid nanoparticles-in-microparticles system for the treatment of ulcerative colitis

Nanoparticle (NP)-based drug delivery systems accumulate in the disrupted epithelium of inflamed colon tissue in ulcerative colitis. However, premature early drug release and uptake or degradation of NPs during their passage through the harsh gastric or intestinal environment compromise their therapeutic outcomes. This study aimed to develop an advanced colitis-targeted hybrid nanoparticles-in-microparticles (NPsinMPs) drug delivery system to overcome the aforementioned challenges. First, sustained drug releasing poly(lactic-co-glycolic acid) NPs were generated and further encapsulated in pH-sensitive Eudragit FS30D MPs to ensure complete drug protection in a gastric-like pH and for selective delivery of NPs to the colon. SEM and confocal microscopy for the NPsinMPs revealed successful NP encapsulation. NPsinMPs prevented drug release in an acidic gastric-like and intestinal-like pH and presented a sustained release thereafter at an ileal and colonic pH, indicating the degradation of the outer pH-sensitive MPs and release of NPs. Furthermore, in vivo imaging of gastrointestinal tract of a colitis mouse orally administered with fluorescent NPsinMPs revealed higher fluorescence intensities selectively in the colon, demonstrating the release of loaded NPs and their concomitant accumulation at the site of colon inflammation. NPsinMPs markedly mitigated experimental colitis in mice indicated by improved histopathological analysis, decreased myeloperoxidase activity, neutrophils and macrophage infiltration, and expression of proinflammatory cytokines in colonic tissues compared with NP-treated mice. The present results show the successful formulation of an NPsinMP-based drug delivery system and provide a platform to improve NP-based colon-targeted drug delivery through improved protection of encapsulated NPs and their payload in the early small intestine.

A novel high doxorubicin-loaded Fe3O4@void@ZnO nanocomposite: pH-controlled drug release and targeted antitumor activity

A novel ferroferric oxide (Fe3O4)@void@zinc oxide (ZnO) nanocomposite was constructed through a template-assisted selective etching method. The experiment results showed that the magnetic saturation value of nanocomposite could reach to 44.07 emu g−1, indicating the favorable magnetic targeting function. The presence of the void endowed the nanocomposite with high drug doxorubicin (DOX) loading capacity (85.65 μg mg−1). The pH-sensitive drug release was realized due to the gating effect of ZnO, and the DOX release rates were 92.7%, 60.8% and 23.4% at the pH values of 5.0, 6.5 and 7.4, respectively (37 °C). Besides, the Fe3O4@void@ZnO-DOX exhibited desirable antitumor effects attributed to their cellular uptake and above advantages. Therefore, the Fe3O4@void@ZnO nanocomposite may serve as a promising drug carrier in cancer therapy and other biomedical applications.

Bistratal Au@Bi2S3 nanobones for excellent NIR-triggered/multimodal imaging-guided synergistic therapy for liver cancer

To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging, novel Au@Bi2S3 core shell nanobones (NBs) (Au@Bi2S3 NBs) with Au nanorods as cores were synthesized. The combination of Au nanorods with Bi2S3 film made the Au@Bi2S3 NBs exhibit ultrahigh photothermal (PT) conversion efficiency, remarkable photoacoustic (PA) imaging and high computed tomography (CT) performance; these Au@Bi2S3 NBs thus are a promising nanotheranostic agent for PT/PA/CT imaging. Subsequently, poly(N-vinylpyrrolidone)-modified Au@Bi2S3 NBs (Au@Bi2S3-PVP NBs) were successfully loaded with the anticancer drug doxorubicin (DOX), and a satisfactory pH sensitive release profile was achieved, thus revealing the great potential of Au@Bi2S3-PVP NBs in chemotherapy as a drug carrier to deliver DOX into cancer cells. Both in vitro and in vivo investigations demonstrated that the Au@Bi2S3-PVP NBs possessed multiple desired features for cancer therapy, including extremely low toxicity, good biocompatibility, high drug loading ability, precise tumor targeting and effective accumulation. Highly efficient ablation of the human liver cancer cell HepG2 was achieved through Au@Bi2S3-PVP NB-mediated photothermal therapy (PTT). As both a contrast enhancement probe and therapeutic agent, Au@Bi2S3-PVP NBs provided outstanding NIR-triggered multi-modal PT/PA/CT imaging-guided PTT and effectively inhibited the growth of HepG2 liver cancer cells via synergistic chemo/PT therapy.

A Novel and Inexpensive Method Based on Modified Ionic Gelation for pH-responsive Controlled Drug Release of Homogeneously Distributed Chitosan Nanoparticles with a High Encapsulation Efficiency

Homogeneous chitosan nanoparticles utilizing EPR effect and pH-sensitive properties have an immense potential for loading and delivery of anticancer drugs. The aim of this study was preparing doxorubicin-loaded homogeneously distributed chitosan nanoparticles by using a simple and mild method, modified ionic gelation, with a very high encapsulation efficiency for controlled and pH-sensitive release. FESEM image revealed that the synthesized chitosan nanoparticles had a uniform spherical morphology with the size range 20–35 nm. The parameters of drug stirring duration, drug amount and nanoparticles formation time were changed to achieve maximum encapsulation efficiency as well as the effect of each parameter on the encapsulation efficiency was studied. The encapsulation efficiency toward doxorubicin under optimal conditions was 81.6±0.8 % (n=5±SD) that was higher than those previously published in literature. The investigations of doxorubicin release from chitosan nanoparticles in four media with different pH values showed a pH-sensitive release with a higher release rate in an acidic environment. The drug release mechanism at all pH values was also evaluated by zero-order, first-order, Higuchi and Korsmeyer-Peppas models. The most consistent model for release curve at four pHs was Korsmeyer-Peppas model. Therefore, we presented a method for the preparation of homogeneous doxorubicin-loaded chitosan nanoparticles with small size that can be industrialized because they were made based on a very simple and green method without the use of a complex system and expensive materials as well as due to their high encapsulation efficiency.

Enhanced intestinal stability and pH sensitive release of quercetin in GIT through gellan gum hydrogels

The objective of the work was to improve the intestinal stability and pH sensitive release of quercetin in the gastrointestinal tract. To achieve this aim, novel quercetin loaded pH sensitive hydrogel beads of gellan gum were developed through an ionic cross-linking technique using calcium chloride (CaCl2) as cross-linking agents. Field emission scanning electron microscopy (FESEM) was used to characterize the morphological appearance of the prepared hydrogel beads. Drug-polymer and drug-CaCl2 interaction were studied by using infrared spectroscopy. The important finding of the study was the formation of stable hydrogel beads at a very low concentration of CaCl2 (0.3 % w/v). There was a drug polymer interaction in addition to polymer and CaCl2 interaction that is confirmed by infrared spectroscopy. All the formulation shows good entrapment efficiencies within the range of 58.56–93.71 %. The prepared beads exhibited a pH responsive swelling behavior with maximum swelling at the simulated intestinal fluid (pH 7.4) (SIF). Hydrogel beads also showed a pH responsive release behavior and sustained release of drug at SIF. Moreover, the intestinal stability of quercetin was improved when encapsulated in gellan gum hydrogel beads in comparison to the solution containing quercetin.

Gold embedded chitosan nanoparticles with cell membrane mimetic polymer coating for pH-sensitive controlled drug release and cellular fluorescence imaging.

In this work, gold embedded chitosan nanoparticles (Au@CS NPs) were fabricated by a one-pot method. The benzaldehyde-terminated poly[(2-methacryloyloxy) ethyl phosphorylcholine] (PMPC) was applied to modification of the gold doped chitosan nanoparticles. The obtained Au@CS-PMPC NPs had the diameter of 135 nm with a narrow distribution. The size of the Au@CS-PMPC NPs, as well as the size of the embedded gold NPs, might be well-controlled by adjusting the feeding ratio between chitosan and HAuCl4. Furthermore, the Au@CS-PMPC NPs showed increased colloidal stability, high drug loading content, pH-responsive drug release, excellent biocompatibility and bright fluorescence emission. The results demonstrated that Au@CS-PMPC NPs showed a great potential for tumor therapy via the combination advantages of pH-sensitive controlled drug release and cellular fluorescence imaging.

Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier.

Potential short interfering RNAs (siRNA) modulating gene expression have emerged as a novel therapeutic arsenal against a wide range of maladies and disorders containing cancer, viral infections, bacterial ailments and metabolic snags at the molecular level. Nanogel, in the current medicinal era, displayed a comprehensive range of significant drug delivery prospects. Biodegradation, swelling and de-swelling tendency, pHsensitive drug release and thermo-sensitivity are some of the renowned associated benefits of nanogel drug delivery system. Global researches have also showed that nanogel system significantly targets and delivers the biomolecules including DNAs, siRNA, protein, peptides and other biologically active molecules. Biomolecules delivery via nanogel system explored a wide range of pharmaceutical, biomedical engineering and agro-medicinal application. The siRNAs and DNAs delivery plays a vivacious role by addressing the hitches allied with chronic and contemporary therapeutic like generic possession and low constancy. They also incite release kinetics approach from slow-release while mingling to rapid release at the targets will be beneficial as interference RNAs delivery carriers. Therefore, in this research, we focused on the latest improvements in the delivery of siRNA loaded nanogels by enhancing the absorption, stability, sensitivity and combating the hindrances in cellular trafficking and release process.

Targeted Drug Delivery of Teniposide by Magnetic Nanocarrier

Background:: Drug delivery technologies adjust drug release profile, absorption, distribution, and elimination for benefiting to the improvement of product efficacy, effectiveness, and safety. The IONPs release drugs via enzymatic activity, changes in physiological conditions such as pH, osmolality radiation, or temperature. In the case of nanoparticles that respond to the magnetic stimulus, the drug directs its action towards the site of a detected magnetic field. Objective:: In this study, the synthesis of a specific drug-delivery system based on magnetic nanocarrier for teniposide as an anticancer drug is reported. The iron oxide@SiO2 core-shell nanoparticles were functionalized with APTS as a spacer then coupling to the DOTA molecules. Anticancer drug of teniposide conjugated to the acidic group of DOTA via an amide bond. Multi-purpose magnetic nanoparticles were synthesized for targeted delivery of teniposide. Methods: Iron oxide nanoparticles were firstly coated with silica and their surface was then modified with aminopropyltriethoxysilane (APTES) through an in situ method. DOTA-NHS was also coupled to Fe3O4@SiO2-APTES via an amide bond formation. In the final step, teniposide as an anti-cancer drug was conjugated with DOTA through ester bonds, and the final compound of Fe3O4@SiO2- APTES-DOTA-Teniposide was obtained. The obtained nanocarrier was evaluated by various analyses. Results:: The multifunctional Fe3O4@SiO2-APTES-DOTA nanocarriers were successfully synthesized and characterized by XRD, FTIR, TGA, and UV-vis techniques. The silica-coated magnetic nanoparticle functionalized with aminopropyl triethoxysilane (APTES) was reacted with an acid group of DOTA, and teniposide was then coupled to DOTA through ester formation bonds. Drug release experiments showed that most of the conjugated teniposide were released within the first 12h. Conclusion:: The fabricated nano-carriers exhibited pH-sensitive drug release behavior, which can minimize the non-specific systemic spread of toxic drugs during circulation whilst maximizing the efficiency of tumor-targeted anticancer drug delivery for this purpose. The prepared teniposidegrafted Fe3O4@SiO2-APTES-DOTA core–shell structure nanoparticles showed a magnetic property with exposure to magnetic fields, indicating a great potential application in the treatment of cancer using magnetic targeting drug-delivery technology and multimodal imaging techniques.

Versatile hollow COF nanospheres via manipulating transferrin corona for precise glioma-targeted drug delivery

Covalent organic framework (COF) nanoparticles for interference-free targeted drug delivery to glioma remains in its infancy. Herein, hollow COF nanospheres with high crystallinity and uniformed sizes were facilely prepared via heterogeneous nucleation-growth. The prepared COF had large surface area/pore volume and exhibited appropriate degradation behavior under acid environment, where therefore doxorubicin was effectively encapsulated and exhibited a pH-sensitive release. Most charmingly, T10 peptide that has high affinity with transferrin (Tf), was conjugated to endow the hollow COF interesting properties to specifically absorb Tf in vivo as Tf corona. For the first time, multifunctional hollow COF nanospheres (the better one named DCPT-2) were successfully synthesized to achieve interference-free cascade-targeting glioma drug delivery across the blood-brain barrier. Treatment with DCPT-2 brought an improved therapeutic outcome with significantly prolonged median survival time and low side effects. This work promised not only a potential protein corona-mediated COF-based drug delivery platform with good biocompatibility for effective and precise brain tumor therapy, but also an endogenous protein corona-mediated targeting strategy for general cancer therapy.

Binary blended co-delivery nanoparticles with the characteristics of precise pH-responsive acting on tumor microenvironment.

Although combined chemotherapy had achieved the ideal efficacy in clinical anti-cancer therapeutic, the issues that need to be addressed are non-targeting and toxic-side effects of small molecule chemical drug (SMCD). In this study, we designed and prepared a novel binary blended co-delivered nanoparticles (BBCD NPs) with pH-responsive feature on tumor microenvironment. The BBCD NPs consists of two kind of drug-loaded NPs, in one of which carboxymethyl chitosan (CMC) and Poly (lactic-co-glycolic acid) (PLGA) were chosen as delivery carrier to load anti-cancer drug vincristine (VCR), named CMC-PLGA-VCR NPs (or CPNPVCR); and in the other of which methoxy poly(ethylene glycol)-poly(β-amino ester) (mPEG-PAE) were chosen as delivery carrier to load anti-fibrotic drug pirfenidone (PFD), named mPEG-PAE-PFD NPs (or PPNPPFD). Then, the two types of NPs (CPNPVCR and PPNPPFD) were physically mixed in mass ratios to form BBCD NPs, which was named CPNPVCR&PPNPPFD. CPNPVCR&PPNPPFD had good encapsulation efficiency and loading capacity, and the particle size distribution was uniform. In cytotoxicity experiments and non-contact co-culture studies in vitro, the model drugs loaded in CPNPVCR&PPNPPFD could respectively target cancer cell and cancer associated fibroblast (CAF) owing to the precise pH-sensitive drug release in the pharmacological targets and show stronger synergism than that of the combined treatment of two free drugs. As a modularity and assemble ability feature in design, BBCD NPs would have the advantages on the terms of concise on preparation process, controllable on quality standard, stable in natural environment storage. The research results can provide scientific evidence for the further development of a novel drug co-delivery system with multi-type cell targets.

Highly fluorinated graphene oxide nanosheets for anticancer linoleic-curcumin conjugate delivery and T2-Weighted magnetic resonance imaging: In vitro and in vivo studies

Carbon-based nanomaterials have received substantial attention as a drug delivery platform for cancer treatment. In the current study, a simple and eco-friendly method was introduced for the preparation of highly fluorinated graphene oxide (FGO), which was subsequently evaluated by standard characterization methods. It was then employed as a carrier for Linoleic acid-curcumin conjugate as an anticancer drug (FGO-Lino-CUR). Finally, the release profile and selective toxicity of FGO-Lino-CUR were investigated and compared with FGO-CUR. It was observed that the pH-sensitive release fitted to Korsmeyer–Peppas model. The accumulated release of Lino-CUR at pH 5.5 was about 20% more than that of pH 7.4. FGO-Lino-CUR exhibited relatively high toxicity (about 60%) against MCF-7 cells which was 20% more than that against MCF10A cells. In vitro MRI studies also revealed that the Lino-CUR loaded FGO with adequate relaxation rate (r2 = 67.12 (s−1mM−1)) and favorable ability to reduce signal intensity in the presence of MCF10A and MCF-7 cells, could be a potential candidate as a negative MRI contrast agent. In vivo anti-tumor studies were performed on 4T1 induced BALB/c breast cancer model. Accordingly, the higher tumor suppression capability of FGO-Lino-CUR was observed with no significant body weight changes during treatment compared with free Lino-CUR. Moreover, the MRI contrast enhancing ability of FGO-Lino-CUR for the in vivo MRI of tumor bearing BALB/c mice, indicated its noticeable ability to create negative contrast. Simple and versatile method for the preparation of the target system as well as acceptable anticancer activity and MRI contrast enhancement, make Lino-CUR loaded FGO as an encouraging candidate for the breast cancer theranostics.

Polymer Nanomedicines with Ph-Sensitive Release of Dexamethasone for the Localized Treatment of Inflammation

Polymer-drug conjugates have several advantages in controlled drug delivery to inflammation as they can accumulate and release the drug in inflamed tissues or cells, which could circumvent the shortcomings of current therapy. To improve the therapeutic potential of polymer-drug conjugates in joint inflammation, we synthesized polymer conjugates based on N-(2-hydroxypropyl) methacrylamide) copolymers labeled with a near-infrared fluorescent dye and covalently linked to the anti-inflammatory drug dexamethasone (DEX). The drug was bound to the polymer via a spacer enabling pH-sensitive drug release in conditions mimicking the environment inside inflammation-related cells. An in vivo murine model of adjuvant-induced arthritis was used to confirm the accumulation of polymer conjugates in arthritic joints, which occurred rapidly after conjugate application and remained until the end of the experiment. Several tested dosage schemes of polymer DEX-OPB conjugate showed superior anti-inflammatory efficacy. The highest therapeutic effect was obtained by repeated i.p. application of polymer conjugate (3 × 1 mg/kg of DEX eq.), which led to a reduction in the severity of inflammation in the ankle by more than 90%, compared to 40% in mice treated with free DEX.