pH-sensitive Drug Delivery System Research Articles

Design and synthesis of drug hydrogels containing carboxymethylcellulose with honeycomb structure and pH-sensitivity as drug delivery systems for adriamycin, metformin, and naproxen

The aim of this research is to prepare and identify functionalized carboxymethylcellulose/mesoporous silica nanohydrogels (CMC/NH2-MCM-41) for obtaining a pH-sensitive system for the controlled release of drugs. The beads of CMC/NH2-MCM-41 nanocomposites were prepared by dispersing NH2-MCM-41 in a CMC polymer matrix and crosslinking with ferric ions (Fe3+). The SEM analysis of samples revealed enhancement in surface porosity of the functionalized nanohydrogel beads compared to the conventional beads. Swelling of the prepared functionalized nanohydrogels was evaluated at various pH values including pH = 7.35–7.45 (simulated body fluid or healthy cells), pH = 6 (simulated intestinal fluid), and pH = 1.5–3.5 (simulated gastric fluid). The swelling of CMC/MCM-41 and CMC/NH2-MCM-41 nanohydrogels at the pH values of simulated body fluid and simulated intestinal fluid is much higher than that of simulated gastric fluid, indicating successful synthesis of pH-sensitive nanohydrogels for drug delivery. The drug loading results showed that drug release in the CMC/NH2-MCM-41 system is much slower than that in the CMC/MCM-41 system. The results of the survival studies for the manufactured systems showed a very good biocompatibility of the designed drug delivery systems for biological applications. By coating the surface of functionalized mesopores with CMC hydrogel, we were able to develop a pH-sensitive intelligent drug delivery system.

Efficient surface modification of silica-alginate nanocarrier as smart drug release platform

A hybrid nanocarrier based on silica-alginate modified by gelatin-folic acid was designed as a pH-sensitive drug delivery system and investigated in the terms of in terms of the amount of doxorubicin loading and release behavior in two different mediums with pH 7.4 and 5.6. The loading content and entrapment efficiency were measured at about 21% and 67%, respectively. The results showed a rapid release of the doxorubicin from the unmodified carrier at initial times (first 24 h). While the use of gelatin-folate modification led to the improvement of the release behavior. Here, the amount of drug released from the silica-alginate carrier after 72 h in a neutral and acidic environment was measured as 82% and 73%, respectively. While using gelatin modification, the amount of released drug decreased to 71% and 63%. These results show that the prepared carrier is sensitive to pH. Furthermore, the cross-linking effect of the gelatin modifier layer on the release pattern was investigated and results indicated the improvement of the release pattern in both acidic and natural media. The findings of this research show the appropriate performance of carriers designed for drug delivery.

Methotrexate-loaded manganese nitrogen dual-doped carbon quantum dots as targeted nano drug-delivery system for potential use in cancer theranostics

The present work highlights manganese nitrogen dual-doped carbon quantum dots as a novel pH-sensitive drug delivery system for the delivery of methotrexate targeted to cancer cells, along with the simultaneous real-time monitoring of cellular uptake and drug delivery using fluorescence imaging. Briefly, methotrexate was conjugated with the as-prepared quantum dots to form a nano drug-delivery system through non-covalent interactions. The developed material demonstrated drug loading efficiency of ∼91 % and a very efficient (∼80 %) pH-responsive drug release at pH 5.5. The cytotoxic properties of the developed nano-platform viz. manganese, nitrogen dual-doped carbon quantum dots, and methotrexate conjugated manganese nitrogen dual-doped carbon quantum dot complex were evaluated in cancer cells (HeLa) and healthy human cells (L929). The conjugated complex demonstrated excellent biocompatibility, high cellular uptake, and a substantial drug release. Healthy human cells were largely unaffected when incubated with both the MTX-conjugated Mn-, N-CQD and the free drug. Additionally, in vitro, the fluorescence bio-imaging potential of the developed nano-platform was also assessed, where the unconjugated (free) quantum dots exhibited better blue fluorescence imaging potential compared to that of conjugated complex, which can be attributed to fluorescence quenching due to the presence of methotrexate. This study highlights the manganese nitrogen dual-doped carbon quantum dots capable of pH-responsive methotrexate drug delivery selective to cancer cells. The combination of drug delivery and fluorescence imaging creates a strong platform for targeted therapy, allowing very precise drug release while accessing non-invasive monitoring of therapeutic response. This method holds great promise for advancing cancer treatment strategies, with the potential for increased efficacy and decreased side effects.

A new candidate for wound dressing materials: s-IPN hydrogel-based highly elastic and pH-sensitive drug delivery system containing pectin and vinyl phosphonic acid

In this study, we developed pH-sensitive semi-interpenetrating network (s-IPN) hydrogels, composed of pectin, 2-hydroxyethyl methacrylate (HEMA), and vinyl phosphonic acid (VPA) using N,N'-methylene bis(acrylamide) (MBA) as a cross-linker with the free-radical polymerization method. The formation of s-IPNs was confirmed by FTIR studies. SEM images showed the addition of VPA to the polymeric matrix of s-IPN hydrogels formed additional microporous structures within the hydrogel network. The s-IPN hydrogel had perfect mechanical features like stretchability, compressibility and elasticity. Additionally, the swelling behavior of s-IPN hydrogels in deionized water and solutions with diverse pH was assessed. To research use as a controlled drug delivery material, the hydrogel was loaded with cimetidine and trimethoprim. At pH 7.2, the in vitro drug release profile was observed and nearly 60 % of the drugs were released from s-IPN hydrogel within 10 h. Additionally, the most appropriate kinetic release model was Higuchi, followed by Korsmeyer-Peppas. Finally, silver sulfadiazine (SSD) was added to s-IPN hydrogel for use as a smart wound dressing material. Antimicrobial analysis of the SSD-loaded s-IPN hydrogel found it had antimicrobial features, inducing 15, 17 and 23 mm inhibition zones against Staphylococcus aureus (gram-positive), Escherichia coli (gram-negative) and Candida albicans (fungus) microorganisms, respectively. In light of the obtained results, based on being easily shapable with appropriate mechanical and physical features, pectin/p(HEMA-co-VPA) and pectin/p(HEMA-co-VPA)@SSD s-IPN hydrogels are potential candidates for use as controlled drug delivery and wound dressing materials in the biomedical field.

In Vitro Antibacterial Activity of a Novel Acid-Activated Antimicrobial Peptide against Streptococcus mutans.

Dental caries is an oral disease associated with infection by microbial biofilm. The metabolic activity of cariogenic bacteria results in a pH decrease in the plaque biofilm, causing tooth demineralization. This acidic environment favors the growth of cariogenic bacteria that are highly resistant to strong acids, which, in turn, produce more acid resulting in a further decrease in the pH of the plaque biofilm. Therefore, the strategy of utilizing the acidic dental plaque microenvironment to prevent and treat dental caries has become a hot research topic in recent years, such as the development of pH-sensitive drug delivery systems. Design of a new acid-activated antibacterial peptide. To design and synthesis an acid targeted antimicrobial peptide with the GWHHFFHFFHFF sequence. Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) testing confirmed its antibacterial activity. Propidium iodide (PI) staining was used to detect nucleic acid leakage. Determination of anti-biofilm activity by biofilm inhibition assay. A phototoxicity study confirmed the phototoxicity of PPIX-P12. MIC and MBC testing confirmed that P12 possessed acid-activated anti-Streptococcus mutans activity. Bactericidal kinetic experiments and propidium iodide (PI) staining experiments showed that P12 killed planktonic S. mutans UA159 cells leading to the leakage of nucleic acids in the acidic medium. Moreover, P12 showed acid-activated anti-biofilms at the early and mature biofilm stages. P12 was conjugated with the phototherapeutic agent protoporphyrin IX (PpIX) to construct the protoporphyrin derivative PpIX-P12. In vitro experiments revealed that PpIX-P12 displayed better antibacterial activity in pH 5.5 medium than in pH 7.2 medium. In conclusion, we designed an acid-activated AMP, which had no antimicrobial activity at neutral pH, but had antimicrobial activity at an acidic pH.

Sustainable Routed Mxene-Based Aminolyzed PU/PCL Film for Increased Oxidative Stress and a pH-Sensitive Drug Delivery System for Anticancer Therapy.

A remarkable challenge in the anticancer drug delivery system is developing an implantable system that can improve the chemotherapeutic effect. Polyurethane is an excellent implantable substrate, with flaws in hydrophobicity. We modified polyurethane via the chemical aminolysis technique to enhance the wettability and protein interaction. The created pores can release the rutin complex incorporated in the polyurethane matrix. In this work, the hybrid polymer matrix consists of Mxene synthesized via a sustainable and simple method by introducing a toxic-free MAX phase and etchants. The incorporation of Mxene and PCL can enhance physicochemical and biological compatibility. Sustainable Mxene increases oxidative stress, cell death, and antibacterial activity, which also resulted in the Mxene@APU/PCL film. Meanwhile, the drug release with respect to pH sensitivity was demonstrated in which Mxene and Mxene@APU/PCL films showed the highest release at pH 5.2; this indicates that the prepared Mxene and aminolyzed polyurethane can function according to the biological system and release the drug from the polymer matrix on slow degradation and swellability. The Mxene and Mxene@APU/PCL films showed 93.2% drug release with oxidative stress on THP-1 cells, which causes rupturing and apoptosis of cancerous cells. The Mxene@APU/PCL film can show great potential in future implantable anticancer drug delivery systems.

Gelatin/polyethylene glycol/g-C3N4 hydrogel with olive oil as a sustainable and biocompatible nanovehicle for targeted delivery of 5-fluorouracil

5-fluorouracil (5-FU) is an anticancer drug with poor water solubility and stability, leading to short plasma half-time and undesired toxic effects on normal tissues. Therefore, novel drug delivery systems (DDS) are required to improve its therapeutic efficiency. The use of nanoparticles in DDS has emerged as a promising method for controlling the release of chemotherapy drugs. In this study, a novel, sustainable and pH-sensitive nanocomposite was designed for the targeted delivery of 5-FU against breast cancer cells. The nanodelivery system based on biocompatible and biodegradable graphitic carbon nitride (g-C3N4) coated with Gelatin (G)/Polyethylene glycol (PEG) biopolymers was prepared by W/O/W double emulsion technique using olive oil and span 80 surfactant. Successful loading of 5-FU into the nanovehicle was confirmed by infrared spectroscopy and X-ray diffraction analyses. Dynamic light scattering corroborated the monodispersity of the nanocarriers, with a typical size between 250 and 300 nm. Scanning electron microscopy images revealed the homogeneity of the nanocomposite and its spherical shape, which was appropriate for DDS. The average zeta potential was + 35.4 mV, demonstrating the good stability of the nanocomposite. The drug loading (47 %) and encapsulation efficiency (89 %) were higher than those reported for other 5-FU nanocarriers. A continuous and controlled 5-FU release from the nanovehicle was observed, and the release rate at pH 5.4 (simulating a cancerous environment) was higher than at pH 7.4 (physiological conditions). Kinetic studies suggested a diffusion controlled mechanism of 5-FU release from the nanocarrier in an acidic environment, while an anomalous transport prevails at neutral pH. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that G/PEG/g-C3N4 had a significant cytotoxicity on MCF-7 breast cancer cells. Flow cytometry indicated that G/PEG/g-C3N4/5-FU led to much higher apoptotic percentage than free 5-FU, while the free drug showed higher percentage of necroptotic cells. This novel bio-nanocomposite shows great potential as a pH-sensitive DDS against breast cancer cells.

Emulsifying Lipiodol with pH-sensitive DOX@HmA nanoparticles for hepatocellular carcinoma TACE treatment eliminate metastasis

Lipiodol-based transcatheter arterial chemoembolization (TACE) is currently the predominant and first-line treatment option recommended by the global standard for unresectable hepatocellular carcinoma (HCC). However, the unstable emulsion of Lipiodol causes a substantial proportion of chemotherapy drugs to enter the circulation system, leading to poor accumulation in cancer tissues and unexpected side effects of chemotherapy drugs. Herein, we emulsified Lipiodol with a pH-sensitive drug delivery system assembled from hexahistidine and zinc ions (HmA) with a super-high loading capacity of doxorubicin (DOX) and a promising ability to penetrate bio-barriers for the effective treatment of HCC by TACE. In vitro tests showed that DOX@HmA was comparable to free DOX in killing HCC cells. Impressively, during the in vivo TACE treatment, the anti-tumor efficacy of DOX@HmA was significantly greater than that of free DOX, indicating that DOX@HmA increased the accumulation of DOX in tumor. Emulsifying Lipiodol with pH-sensitive DOX@HmA significantly inhibited cell regeneration and tumor angiogenesis and decreased the systemic side effects of chemotherapy, especially by suppressing pulmonary metastasis in liver VX2 tumors in rabbits by inhibiting epithelial–mesenchymal transition (EMT). Emulsifying tumor microenvironment-responsive drug delivery systems (DDSs) with Lipiodol could be a new strategy for clinical TACE chemotherapy with potentially enhanced HCC treatment.

Synthesis and characterization of bio-nanocomposite hydrogel beads based on magnetic hydroxyapatite and chitosan: a pH-sensitive drug delivery system for potential implantable anticancer platform

Synthesis and characterization of bio-nanocomposite hydrogel beads based on magnetic hydroxyapatite and chitosan: a pH-sensitive drug delivery system for potential implantable anticancer platform

Hybrid nanoarchitecture of gelatin-modified silica-chitosan as an efficient delivery platform and functional role of crosslinking

A novel hybrid of a quercetin-loaded silica-chitosan, modified by crosslinked gelatin-folate was developed in the current study as a pH-sensitive drug delivery system. The entrapment efficiency of quercetin was measured at about 77%. The drug release pattern was investigated in acidic and natural media (pH 5.6 and pH = 7.4) for 96 h. In-vitro drug release from unmodified carriers exhibited a rapid release in the early times (57 and 39% after 24 h in acidic and neutral media), which was followed by a slower release. However, the release behavior was improved after modifying the carrier with a gelatin-folate layer. In addition, a further release rate was observed for the gelatin-modified carrier in an acidic medium (31% after 24 h) compared to a neutral condition (20% after 24 h), confirming pH-sensitive behavior. Furthermore, the cumulative release of quercetin from the crosslinked gelatin-folate modified silica-chitosan carrier followed an approximately slow release, so that 23% and 15% of the drug was released after 24 h in acidic and natural conditions, respectively. The release date was described by the Higuchi model, suggesting that both diffusion and polymer swelling control the release process. The high drug loading, pH-triggered behavior, and controlled release of the developed hybrid drug platform, combined with low toxicity, render this designed carrier applicable in targeted drug delivery.

Doxorubicin-loaded Niosomes functionalized with gelatine and alginate as pH-responsive drug delivery system: A 3D printing approach

Despite many efforts, breast cancer remains one of the deadliest cancers and its treatment faces challenges related to cancer drug side effects and metastasis. Combining 3D printing and nanocarriers has created new opportunities in cancer treatment. In this work, 3D-printed gelatin-alginate nanocomposites containing doxorubicin-loaded niosomes (Nio-DOX@GT-AL) were recruited as an advanced potential pH-sensitive drug delivery system. Morphology, degradation, drug release, flow cytometry, cell cytotoxicity, cell migration, caspase activity, and gene expression of nanocomposites and controls (Nio-DOX and Free-DOX) were evaluated. Results show that the obtained niosome has a spherical shape and size of 60–80 nm. Sustained drug release and biodegradability were presented by Nio-DOX@GT-AL and Nio-DOX. Cytotoxicity analysis revealed that the engineered Nio-DOX@GT-AL scaffold had 90 % cytotoxicity against breast cancer cells (MCF-7), whereas exhibited <5 % cytotoxicity against the non-tumor breast cell line (MCF-10A), which was significantly more than the antitumor effect of the control samples. Scratch-assay as an indicator cell migration demonstrated a reduction of almost 60 % of the covered surface. Gene expression could provide an explanation for the antitumor effect of engineered nanocarriers, which significantly reduced metastasis-promoting genes (Bcl2, MMP-2, and MMP-9), and significantly enhanced the expression and activity of genes that promote apoptosis (CASP-3, CASP-8, and CASP-9). Also, considerable inhibition of metastasis-associated genes (Bax and p53) was observed. Moreover, flow-cytometry data demonstrated that Nio-DOX@GT-AL decreased necrosis and enhanced apoptosis drastically. The findings of this research can confirm that employing 3D-printing and niosomal formulation can be an effective strategy in designing novel nanocarriers for efficient drug delivery applications.

Oral hydrogel nanoemulsion co-delivery system treats inflammatory bowel disease via anti-inflammatory and promoting intestinal mucosa repair

BackgroundDue to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it’s urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon.ResultsIn this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment.ConclusionsIt’s suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD.Graphical

Preparation of carboxymethylcellulose / ZnO / chitosan composite hydrogel microbeads and its drug release behaviour

In this study, a novel carboxymethylcellulose / ZnO / chitosan (CMC / ZnO / Cs) hydrogel microbeads loaded with crosslinked porous starch / curcumin (CPS / Cur) were designed and prepared to improve the encapsulation efficiency of curcumin for drug delivery to specific sites. It was found that the total pore volume of crosslinked porous starch (CPS) was increased by 1150 % when compared to the native starch (NS), and the adsorption ratio of curcumin by CPS was enhanced by 27 % when compared to NS. Secondly, the swelling ratio of composite hydrogel microbeads was within 25 % in an acidic environment at pH 1.2, and the swelling ratio of hydrogel microbeads sharply increased to 320 % ~ 370 % at pH 6.8 and 7.4. In addition, the results of in vitro simulated release experiments showed that the released amount of hydrogel microbeads loaded with NS/Cur and CPS/Cur in SGF were within 7 % in simulated gastric fluid (SGF). The highest released amount of curcumin was 65.26 % for hydrogel beads loaded with CPS/Cur, which was 26 % lower than that of hydrogel microbeads loaded with Cur in simulated intestinal fluid (SIF). In simulated colonic fluid (SCF), the released amount of hydrogel microbeads loaded with CPS/Cur and Cur were 73.96 % and 91.69 %, respectively. In conclusion, pH-sensitive drug delivery system with good drug stability and bioavailability were successfully prepared with carboxymethylcellulose / ZnO / chitosan bead, suitable targeting drug delivery to the small intestine.

Research Progress of a Pesticide Polymer-Controlled Release System Based on Polysaccharides.

In recent years, with the development of the nanomaterials discipline, many new pesticide drug-carrying systems-such as pesticide nano-metal particles, nano-metal oxides, and other drug-carrying materials-had been developed and applied to pesticide formulations. Although these new drug-loading systems are relatively friendly to the environment, the direct exposure of many metal nanoparticles to the environment will inevitably lead to potential effects. In response to these problems, organic nanomaterials have been rapidly developed due to their high-quality biodegradation and biocompatibility. Most of these organic nanomaterials were mainly polysaccharide materials, such as chitosan, carboxymethyl chitosan, sodium alginate, β-cyclodextrin, cellulose, starch, guar gum, etc. Some of these materials could be used to carry inorganic materials to develop a temperature- or pH-sensitive pesticide drug delivery system. Herein, the pesticide drug-carrying system developed based on polysaccharide materials, such as chitosan, was referred to as the pesticide polymer drug-carrying system based on polysaccharide materials. This kind of drug-loading system could be used to protect the pesticide molecules from harsh environments, such as pH, light, temperature, etc., and was used to develop the function of a sustained release, targeted release of pesticides in the intestine of insects, and achieve the goal of precise application, reduction, and efficiency of pesticides. In this review, the recent progress in the field of polysaccharide-based polymer drug delivery systems for pesticides has been discussed, and suggestions for future development were proposed based on the current situation.

Alginate/carboxymethylcellulose-based hydrogels as pH-sensitive drug delivery systems: facile production with enhanced degradation, thermal and mechanical properties

Alginate/carboxymethylcellulose-based hydrogels as pH-sensitive drug delivery systems: facile production with enhanced degradation, thermal and mechanical properties

Cross-Linked Electrospun pH-Sensitive Nanofibers Adsorbed with Temporin-Ra for Promoting Wound Healing.

Bioresponsive nanodrug delivery systems have excellent potential in tissue engineering applications. Poly-anionic and poly-cationic biopolymers have provided a superior platform for designing pH-sensitive drug delivery systems. In this regard, hyaluronic acid-chitosan-polyvinyl alcohol complex nanofibers with high quality and reproducibility were produced by optimizing the solution preparation process. In addition, the synthesized composite nanofiber, with 66.82 kN/mm toughness, 200% swelling ratio, and 60% porosity, exhibited excellent properties to meet the requirements of the ideal wound dressing. Green cross-linking with citric acid prevented the destruction of the nanofiber even after prolonged immersion in biological solutions. ζ potential studies demonstrated that the synthesized nanofiber has a negative surface charge (∼-30) at physiological pH. The pKa of the temporin-Ra peptide is about 10, and as a result the peptide molecules have a net positive charge in physiological conditions. Therefore, peptide molecules immobilized on the synthesized scaffold based on surface adsorption. In vivo evaluation has proven that the wound bed has an alkaline environment, facilitating peptide release from the nanofiber scaffold. Electrospun nanofibers can imitate the architecture of the extracellular matrix for accelerating wound healing. In vitro investigation showed better adhesion, proliferation, migration, and fibroblast cell growth on peptide-loaded nanofiber samples than other groups. In vivo studies on full-thickness wounds in the mouse model indicated that the designed nanofiber was gradually absorbed without causing dryness or infection. On day 6, the peptide-loaded nanofiber revealed 60% wound closure compared to the control group (17%). In addition, based on histological studies, the composite nanofiber demonstrated excellent tissue repair ability, hence these active nanofiber mats can be a good alternative to existing wound dressings. Gene expression studies show that the antimicrobial peptide promotes the inflammatory phase of wound healing in a shorter time frame by accelerating the tumor necrosis factor-α cytokine response.

PH-activated antibiofilm strategies for controlling dental caries.

Dental biofilms are highly assembled microbial communities surrounded by an extracellular matrix, which protects the resident microbes. The microbes, including commensal bacteria and opportunistic pathogens, coexist with each other to maintain relative balance under healthy conditions. However, under hostile conditions such as sugar intake and poor oral care, biofilms can generate excessive acids. Prolonged low pH in biofilm increases proportions of acidogenic and aciduric microbes, which breaks the ecological equilibrium and finally causes dental caries. Given the complexity of oral microenvironment, controlling the acidic biofilms using antimicrobials that are activated at low pH could be a desirable approach to control dental caries. Therefore, recent researches have focused on designing novel kinds of pH-activated strategies, including pH-responsive antimicrobial agents and pH-sensitive drug delivery systems. These agents exert antibacterial properties only under low pH conditions, so they are able to disrupt acidic biofilms without breaking the neutral microenvironment and biodiversity in the mouth. The mechanisms of low pH activation are mainly based on protonation and deprotonation reactions, acids labile linkages, and H+-triggered reactive oxygen species production. This review summarized pH-activated antibiofilm strategies to control dental caries, concentrating on their effect, mechanisms of action, and biocompatibility, as well as the limitation of current research and the prospects for future study.

Effects of natural polymers for enhanced silica-based mesoporous drug carrier

A nanocarrier consisting of quercetin-loaded mesoporous silica as core, chitosan as initial coating, and gelatin polymer as an exterior coating was developed based on the sol-gel method to be used as a pH-sensitive drug delivery system. The structure, chemical properties, surface area, and morphology of coated mesoporous silica containing quercetin were addressed by XRD, FTIR, and BET analyses. The drug loading and entrapment efficiency were measured at about 18% and 73%, respectively, indicating the high loading capacity of the drug into the porous carrier. Also, the drug release pattern was traced in two different phosphate saline buffer solutions (pH 5.6 and pH = 7.4). According to the results, a rapid release in the early hours was observed, which was significantly improved by a chitosan polymer coating. Here 43% of the drug was released after 24 h in acidic buffer, while only 27% of the drug was released after 24 h in a neutral medium. Also, the use of gelatin was led to a relatively controlled release pattern. Moreover, the amount of drug release from gelatin-coated nanocarrier in an acidic medium was decreased down to 34% and 69% after 24 and 48 h, confirming the pH-sensitive behavior. The kinetic study demonstrated that the quercetin release from silica-based carriers follows the Higuchi model. Toxicity studies also showed that the viability cell of MCF-7 cells after 24 and 48 h exposure to drug-free carriers was 95% and 92%, respectively, indicating low carrier toxicity. According to the findings, the developed nanocarrier manufactured can be considered as a suitable option for intelligent drug delivery.

Facile preparation of pH-sensitive biocompatible alginate beads havening layered double hydroxide supported metal-organic framework for controlled release from doxorubicin to breast cancer cells

In the present study, a pH-sensitive controlled drug delivery system was prepared from alginate beads impregnated with AlCu layered double hydroxides (LDH) supported copper metal-organic framework (Alg-DOX-Cu MOF-LDH beads) for controlled release from doxorubicin (DOX) to breast cancer cells. The physicochemical properties of Alg-DOX-Cu MOF-LDH beads were determined by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), field emission scanning electron microscopy (FE-SEM), and Zeta potential. The in vitro release studies showed that the Alg-DOX-Cu MOF-LDH beads had more controlled drug release than the DOX-Cu MOF-LDH and in vitro release of DOX from both carriers showed pH-response release behavior. The kinetic adsorption studies also confirmed that the drug release from the DOX-Cu MOF-LDH and Alg-DOX-Cu MOF-LDH beads well obey the Korsmeyer-Peppas model. Meanwhile, in vitro cytotoxicity and DAPI tests on L929 (non-cancerous cells) and MCF-7 (human breast cancer cells) clearly showed that the prepared AlCu LDH and Cu MOF-LDH systems had good biocompatibility. Whereas, Alg-DOX-Cu MOF-LDH beads had higher cytotoxicity effects as a result of the controlled release of DOX to MCF-7 cells. These results suggested that the Alg-DOX-Cu MOF-LDH beads can be used as an excellent drug delivery system for cancer therapy and other biomedical applications.

Development of chitosan/halloysite/graphitic‑carbon nitride nanovehicle for targeted delivery of quercetin to enhance its limitation in cancer therapy: An in vitro cytotoxicity against MCF-7 cells

Although quercetin (QC) has valuable advantages, its low water solubility and poor permeability have limited its utilization as an anticancer drug. In this study, hydrogel nanocomposite of chitosan (CS), halloysite (HNT), and graphitic‑carbon nitride (g-C3N4) was prepared and loaded by QC using a water in oil in water emulsification process to attain QC sustained-release. Using g-C3N4 in the HNT/CS hydrogel solution enhanced the entrapment effectiveness (EE %) by up to 86 %. The interactions between QC and nanoparticles caused the nanocomposite pH-responsive behavior that assists in minimizing the side effect of the anticancer agent by controlling the burst release of QC at neutral conditions. According to DLS analysis, the size of the QC-loaded nanovehicle was 454.65 nm, showing that nanoparticles are highly monodispersed, which also was approved by FE-SEM. Additionally, Zeta potential value for the fabricated drug-loaded nanocarrier is +55.23 mV displaying that nanoparticles have good stability. The hydrogel nanocomposite structure's completeness was shown by FTIR pattern, and quercetin was included into the designed delivery system based on XRD data. Besides, the drug release profile indicated that a targeted sustained-release and pH-sensitive release of anticancer drug with the 96-hour extended-release were noticed. In order to comprehend the process of QC release at pH 5.4 and 7.4, four kinetic models were employed to find the best-suited model according to the acquired release data. Finally, the MTT experiment revealed considerable cytotoxicity against breast cancer cells, MCF-7 cell line was experimented in vitro, for the CS/HNT/g-C3N4 targeted delivery system in comparison to QC as a free drug. According to the above description, the CS/HNT/g-C3N4 delivery platform is a unique pH-sensitive drug delivery system for anticancer purposes that improves loading as well as sustained-release of quercetin.