Controlled Drug Release Behavior Research Articles

Cross-linker engineered poly(hydroxyethyl methacrylate) hydrogel allows photodynamic and photothermal therapies and controlled drug release

Here, we disclose the synthesis of poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels incorporating a squaraine dye (Sq) as a chemical crosslinker, viz. Sq@PHEMA. Photothermal and photodynamic features of Sq@PHEMA hydrogels are evaluated in detail. It is noteworthy that Sq@PHEMA induces hyperthermia upon irradiation with an 808 nm laser. Furthermore, Sq@PHEMA enables the generation of reactive oxygen species (ROS) upon irradiation with red light. To our delight, Sq@PHEMA hydrogels can be used as efficient dual photosensitizers pertinent to both PDT and PTT simultaneously. Finally, the hydrogels are loaded with methotrexate (MTX) to investigate controlled drug release behavior. It is noted that Sq@PHEMA hydrogels are promising candidates as drug delivery systems since on-demand MTX release is feasible upon irradiation. In summary, we effectively demonstrate that hydrogel cross-linker engineering allows for synergistic photodynamic and photothermal therapy. Furthermore, drug delivery is also feasible with the Sq@PHEMA core.

From biopolymer matrix to medicine: the drug delivery dynamics of amoxicillin-loaded PVA/SA/ZnONPs hydrogels

This research presents a comprehensive study of Polyvinyl alcohol/Sodium alginate/Zinc oxide nanoparticles (PVA/SA/ZnONPs) and PVA/SA/ZnONPs/Amoxicillin (AMX) hydrogels, demonstrating their potential for various biomedical applications. A comparative analysis of their swelling behavior, in vitro biodegradation, antibacterial properties, and drug release profiles was performed. The hydrogels demonstrated distinct swelling characteristics, with the PVA/SA/ZnONPs/AMX hydrogel showing a higher initial swelling ratio. This behavior, likely due to the increased hydrophilicity from AMX, subsequently decreased over time, indicating AMX release into the environment. The biodegradation study highlighted a faster degradation rate for the PVA/SA/ZnONPs/AMX hydrogel, suggesting its suitability for applications requiring rapid degradation, such as drug delivery systems. Regarding antibacterial properties, the PVA/SA/ZnONPs/AMX hydrogel showed significant antibacterial activity against both Escherichia coli and Staphylococcus aureus, making it a strong candidate for biomedical applications necessitating antibacterial activity. Additionally, the drug release study presented a gradual and controlled release of AMX from the hydrogels over time, demonstrating their potential for sustained drug delivery applications. This research underscores the potential of PVA/SA/ZnONPs/AMX hydrogel, particularly for biomedical applications, especially in wound healing and drug delivery domains, given its potent antibacterial properties and controlled drug release behavior.

Development of Poly(vinyl alcohol)-Chitosan Composite Nanofibers for Dual Drug Therapy of Wounds.

Current trends in localized drug delivery are emphasizing the development of dual drug-loaded electrospun nanofibers (NFs) for an improved therapeutic effect on wounds, especially infected skin wounds. The objective of this study was to formulate a new healing therapy for an infected skin wound. To achieve this goal, this study involved the development and characterization of poly(vinyl alcohol) (PVA)/chitosan nanofibers loaded with ciprofloxacin and rutin hydrate. Polymers and drugs were used in different ratios. Nanofiber morphology was studied by scanning electron microscopy, thermal stability by thermogravimetric analysis, structural determination by the X-ray diffraction method, and integrity by Fourier transform infrared spectroscopy. Dissolution studies were performed to check the drug release behavior of the formulations. Antibacterial studies were performed against Staphylococcus aureus and Pseudomonas aeruginosa. The wound healing efficiency of dual drug-loaded nanofibers was measured by a full-thickness excisional wound model of rabbits. The fabricated nanofibers were smooth in morphology. According to FTIR findings, the drugs remained intact in the nanofibers. The results of swelling ratio and porosity revealed that the pore size was increased as the amount of chitosan was increased up to 30% but a further increase in chitosan concentration reduced the swelling ratio and porosity. Drug release studies of nanofibers depicted an initial burst effect and afterward controlled drug release behavior. Drug-loaded nanofibers showed better activity against S. aureus than P. aeruginosa. The antibacterial efficacy of rutin hydrate with ciprofloxacin was improved compared to that of the formulation having rutin hydrate only, likely due to the additive effect in activity. Based on wound healing studies, nanofibrous membranes acted as a promising wound dressing material as compared to the commercial wound healing formulation. Drug-loaded polymeric nanofibers were successfully fabricated by using an electrospinning method. These nanofibers showed an efficient ability to deliver drugs and treat infected wounds.

3D Printed Ion-Responsive Personalized Transdermal Patch.

Microneedle patches are easy-to-use medical devices for transdermal administration. However, the insufficient insertion of microneedles due to the gap between planar patches and contoured skin affects drug delivery. Herein, we formulate a prepolymer for high-fidelity three-dimensional (3D) printed personalized transdermal patches. With the excellent photoinitiation ability of 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine (Tz), a high-fidelity and precise microneedle patch is successfully fabricated. Upon irradiation of the white illuminator, the doped gold nanoparticles (AuNPs) in the patch release heat and promisingly induce sweat production. With the introduction of Na+, the dominant component of sweat, the curvature of the produced transdermal patch is observed due to the ion-induced network rearrangement. The alkanethiol-stabilized AuNP with an end group of a carboxyl group causes controlled drug release behavior. Furthermore, the irradiation-induced photothermal heating of AuNP can facilitate the sustainability of drug release thanks to the substantially increased particle size of AuNP. These findings demonstrate that the developed prepolymer is a promising candidate for the production of transdermal patches fitting the curvature of the body surface.

Electrospun multi-chamber core-shell nanofibers and their controlled release behaviors: A review.

Core-shell structure is a concentric circle structure found in nature. The rapid development of electrospinning technology provides more approaches for the production of core-shell nanofibers. The nanoscale effects and expansive specific surface area of core-shell nanofibers can facilitate the dissolution of drugs. By employing ingenious structural designs and judicious polymer selection, specialized nanofiber drug delivery systems can be prepared to achieve controlled drug release. The synergistic combination of core-shell structure and materials exhibits a strong strategy for enhancing the drug utilization efficiency and customizing the release profile of drugs. Consequently, multi-chamber core-shell nanofibers hold great promise for highly efficient disease treatment. However, little attention concentration is focused on the effect of multi-chamber core-shell nanofibers on controlled release of drugs. In this review, we introduced different fabrication techniques for multi-chamber core-shell nanostructures, including advanced electrospinning technologies and surface functionalization. Subsequently, we reviewed the different controlled drug release behaviors of multi-chamber core-shell nanofibers and their potential needs for disease treatment. The comprehensive elucidation of controlled release behaviors based on electrospun multi-chamber core-shell nanostructures could inspire the exploration of novel controlled delivery systems. Furthermore, once these fibers with customizable drug release profiles move toward industrial mass production, they will potentially promote the development of pharmacy and the treatment of various diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Electrospun PLLA/PEI nanofibers for controlled drug release behaviors and antibacterial efficiency

This study focused on the poly(L-lactic acid) (PLLA) polymer matrices by adding branched polyethyleneimine (PEI) as an aminolysis agent. Electrospun nanofibers were made by blending PLLA and PEI at various weight ratios (85-15, 75-15, and 65-35) and mixing times (0.5 h, 1 h, and 2 h). Amine groups were introduced into the nanofiber matrices, as confirmed by Fourier-transform infrared (FTIR) spectroscopy. The PLLA-PEI reaction was affected by mixing time, as shown by rheological measurements of absolute viscosity and surface tension. As a result, the nanofiber diameters decreased up to 42% and 89% with longer mixing time and higher PEI content, respectively. The aminolysis reaction rate increased up to 6.6 times with more PEI. Furthermore, the nanofibers had improved host-guest interactions, as demonstrated by contact angle, drug release, dye adsorption and water adsorption tests. The drug-loading capacity of the nanofibers was enhanced by PEI modification, as indicated by the release profile of tetracycline hydrochloride. The nanofibers also revealed more than 99.99% antibacterial activity due to the presence of the amine groups in PEI. Optimum mixing time and polymer ratio were proved to be substantial parameters to reach appropriate nanofiber and improve spinnability for further biomedical applications.

Synthesis and characterization of poly (acrylamide‐co‐acrylic acid)/chitosan (derived from fish scales) for controlled release of amoxicillin drug

AbstractChitosan (CS) can be extracted from waste fish scales through a series of chemical processes, including demineralization, deproteinization, and deacetylation. The biomaterial poly (acrylamide [AM]‐co‐acrylic acid [AA])/CS is a unique superabsorbent material synthesized through the free radical graft copolymerization method by using AM, AA, and CS powder. During synthesis, ammonium persulfate is used as an initiator, and N, N′‐methylene bisacrylamide is used as a cross‐linker. Scanning electron microscopy and Fourier transform infrared spectroscopy have been studied to know about the morphology and structure of the synthesized superabsorbent materials. The water absorbency of the material continuously increases from day 1 to day 30. The thermogravimetric analysis (TGA) and derivative thermogravimetry (DTG) of the superabsorbent material show adequate thermal stability. The X‐ray diffraction (XRD) analysis indicates that the synthesized biomaterial is virtually amorphous in nature. The percentage of biodegradability increases with time. The encapsulation efficiency of amoxicillin drugs is around 70%, which indicates that the biomaterial is highly efficient for drug release applications. The synthesized novel biomaterial is a low‐cost, eco‐friendly, and thermally stable hydrogel that can be effectively used in drug release applications.Highlights Chitosan (CS)‐based hydrogels are highly pH‐sensitive towards drug release. The biodegradability and swelling behavior of the synthesized biomaterial were studied by adopting a suitable methodology. The novel material formed was characterized by using Fourier transform infrared spectroscopy, TGA, and Scanning electron microscopy. The encapsulation efficiency, kinetic study, and controlled drug release behavior of the amoxicillin drug were studied in solutions of simulated gastric fluid and phosphate‐buffered saline. The material developed in this study shows good performance in controlled drug delivery, and is therefore suitable for manufacturing medical devices used in drug delivery.

68 Ga-labeled, imatinib encapsulated, theranostic liposomes: Formulation, characterization, and in vitro evaluation of anticancer activity.

Cancer is still a global health problem. Among cancer types, breast cancer is the most frequently diagnosed one, and it causes a high mortality rate if not diagnosed in the early stages. In our study, imatinib encapsulated, nanosized, neutral/cationic liposome formulations were prepared as theranostic agents for breast cancer. After the characterization studies in which all liposomes exhibited proper profile owing to their particle size between 133 and 250 nm, polydispersity index valueslower than 0.4, neutral and cationic zeta potential values, and high drug encapsulation efficiency, controlled drug release behaviors with zero-order kinetic were obtained. The higher than 90% radiolabeling efficiency values were obtained thanks to the determination of optimum radiolabeling condition (80°C temperature, 5 mCi radioactivity, and 10 min incubation period). According to the resazurin assay evaluating the cytotoxic profile of liposomes on MCF7 cells, neutral empty liposome was found as biocompatible, while both cationic liposomes (empty and drug-loaded ones) exhibited high nonspecific cytotoxicity at even low drug concentration due to the existence of stearyl amine in the formulations. However, dose-dependent cytotoxic effect and the highest cellular binding capacity were obtained by imatinib loaded neutral liposomes. In conclusion, 68 Ga-radiolabeled, imatinib-loaded, neutral, nanosized liposome formulation is the most promising one as a theranostic agent among all formulations.

Targeted co-delivery of paclitaxel and chrysin by hyaluronate/chitosan-coated polymeric nanoparticles for prostate cancer chemotherapy

Chemotherapy is one of the most common therapeutic approaches in most cancers like prostate cancer, which has always faced limitations. The purpose of the present study was to design and prepare the targeted polymeric nanoparticles for the co-delivery of Paclitaxel (PTX) and Chrysin (CHR) to prostate cancer cells to improve the PTX therapeutic efficacy. Through the current research, the surface modification of the PTX/CHR-loaded PCL-PEG-PCL nanoparticles with chitosan and hyaluronic acid (PTX/CHR-PCEC-CS/HA) was successfully performed through the physical adsorption process. SEM results showed that this polymeric NPs had a homogeneous spherical structure. The encapsulation efficiency was 78.6 and 93.28% for CHR and PTX, respectively. It is important to mention that the controlled drug-release behavior of the PTX/CHR-PCEC-CS/HA was also investigated. The results demonstrated that the dual drug-loaded PCEC-CS/HA NPs had a significant effect on reducing the survival of the cancer. Also, the results exhibited that the cytotoxicity of the dual drug-loaded polymeric NPs in the PC3 cell line is significantly higher than in the HUVEC cell line. Based on the findings, the targeted PTX/CHR-PCEC-CS/HA NPs could be employed as a suitable candidate for the effective treatment of the prostate cancer.

Polypyrrole nanoparticles loaded with doxorubicin for pH-responsive combinational photothermal-chemotherapy of cancer cells

The combined treatment method integrated photothermal therapy (PTT) with chemotherapy is extremely promising owing to the synergistic therapeutic effect as compared to single PTT or chemotherapy. To facilitate more novel and facile photothermal-chemotherapy drugs as well as promote controllable combination therapy, we have developed a mild and facile method to fabricate polymer polypyrrole (PPy)-doxorubicin (DOX) nanoparticles (NPs) as pH-responsive drug nanocarriers for synergistic photothermal-chemotherapy. In the nanoplatform, poly-L-lysine (PLL)-modified PPy serves as the photothermal material, and (DOX) molecules are adopted as the chemotherapy agent. Based on the cross-linking reaction of glutaraldehyde, DOX molecules are flexibly and efficiently assembled on the surface of PLL-modified PPy NPs. The obtained PPy-DOX NPs possess high photothermal effect, superior loading capacity of DOX, and controlled drug release behavior. The combination photothermal-chemotherapy based on PPy-DOX NPs has significantly enhanced the antitumor therapy effect. In general, the designed PPy-DOX NPs may be a potential drug delivery nanoplatform for cancer combination therapy.

A Novel Topical Formulation of the Leishmaniasis Drug Glucantime as a Nanostructured Lipid Carrier-Based Hydrogel.

Leishmaniasis is a parasitic disease caused by Leishmania parasites. Meglumine antimoniate, or Glucantime, is the primary drug used to treat this disease. Glucantime with a standard painful injection administration route has high aqueous solubility, burst release, a significant tendency to cross into aqueous medium, rapid clearance from the body, and insufficient residence time at the injury site. Topical delivery of Glucantime can be a favorable option in the treatment of localized cutaneous leishmaniasis. In this study, a suitable transdermal formulation in the form of nanostructured lipid carrier (NLC)-based hydrogel containing Glucantime was prepared. In vitro drug release studies confirmed controllable drug release behavior for hydrogel formulation. An invivo permeation study on healthy BALB/C female mice confirmed appropriate penetration of hydrogel into the skin and sufficient residence time in the skin. In vivo performance of the new topical formulation on the BALB/C female mice showed a significant improvement in reduction of leishmaniasis wound size, lowering parasites number in lesions, liver, and spleen compared with commercial ampule. Hematological analysis showed a significant reduction of the drug's side effects, including variance of enzymes and blood factors. NLC-based hydrogel formulation is proposed as a new topical administration to replace the commercial ampule.

Sustainable functionalized chitosan based nano-composites for wound dressings applications: A review

Functionalized chitosan nanocomposites have been studied for wound dressing applications due to their excellent antibacterial and anti-fungal properties. Polysaccharides show excellent antibacterial and drug-release properties and can be utilized for wound healing. In this article, we comprise distinct approaches for chitosan functionalization, such as photosensitizers, dendrimers, graft copolymerization, quaternization, acylation, carboxyalkylation, phosphorylation, sulfation, and thiolation. The current review article has also discussed brief insights on chitosan nanoparticle processing for biomedical applications, including wound dressings. The chitosan nanoparticle preparation technologies have been discussed, focusing on wound dressings owing to their targeted and controlled drug release behavior. The future directions of chitosan research include; a) finding an effective solution for chronic wounds, which are unable to heal completely; b) providing effective wound healing solutions for diabetic wounds and venous leg ulcers; c) to better understanding the wound healing mechanism with such materials which can help provide the optimum solution for wound dressing; d) to provide an improved treatment option for wound healing.

PH-responsive nanocomposite hydrogel for simultaneous prevention of postoperative adhesion and tumor recurrence.

Abdominal adhesion and tumor recurrence are two thorny problems in the postoperative treatment of abdominal tumors. Although important progress has been made in the application of hydrogels in adjuvant therapy after tumor surgery, most of the products can not effectively combine the prevention of abdominal adhesion and the removal of residual cancer cells. In this study, a nanocomposite hydrogel (Col-APG-Cys@HHD) was prepared by crosslinking collagen and recombinant albumin nanoparticles (HHD NPs) with aldehydeylated polyethylene glycol (APG6K) followed by immobilizing zwitterionic cysteine (Cys) to one surface. One surface of the hydrogel adhered to the postoperative wound due to the adhesive properties of collagen, while the other surface coated with cysteine formed a hydration layer to hinder the stick of proteins and cells, thereby reducing the adhesion between tissues. Additionally, Col-APG-Cys@HHD hydrogel disintegrated under acidic condition and released HHD NPs that targeted into cancer cells and released drugs in response to low pH environment. The in vivo experiments' results demonstrated that Col-APG-Cys@HHD hydrogel could prevent intraperitoneal adhesions and inhibit tumor growth with minimal side effects, providing a potential strategy for the hydrogel-based drug delivery system in postoperative adjuvant therapy of tumors. STATEMENT OF SIGNIFICANCE: Tissue adhesion and tumor recurrence usually occur after abdominal tumor surgery. Hydrogels have been widely studied in adjuvant treatment of abdominal tumors, but their synergy in terms of controllable drug release and anti-peritoneal adhesion still needs to be improved. Herein, a nanocomposite hydrogel (Col-APG-Cys@HHD) was designed and constructed with one side that was tissue adhesive and the other side as antifouling. Additionally, the Col-APG-Cys@HHD hydrogel showed controlled drug release behavior in response to a pH gradient (6.5 to 5.5). This was conducive to its dissociation in an acidic tumor environment followed by the release of nanoparticles that entered into tumor cells and delivered docetaxel . To sum up, the Col-APG-Cys@HHD hydrogel demonstrated synergistic therapy for prevention of abdominal adhesion and tumor recurrence after abdominal tumor surgery.

Construction of a new dual-drug delivery system based on stimuli-responsive co-polymer functionalized D-mannose for chemotherapy of breast cancer

In this work, we aimed to prepare the new blue-emissive carbon dots (CDs)-supported glyco-copolymer brushes functionalized D-mannose for targeted co-anticancer drug delivery to the breast cancer cells. Typically, the N-isopropyl acrylamide (NIPAM) and maleic anhydride (MAH) were copolymerized on the silica functionalized CDs surface via free-radical polymerization (CDs-poly(NIPAM-co-MAH)). Then, the synthesized CDs-poly(NIPAM-co-MAH) was functionalized with D-mannose (CDs-poly(NIPAM-co-MAH)-D-Man). The success of the nanocomposite synthesis was approved via several common characterization techniques. Thermal gravimetric analysis (TGA) analysis determined the percentage of polymer brush summed with D-mannose (D-Man) at about 12%. The size of CDs-poly(NIPAM-co-MAH)-D-Man was obtained at 30–42 nm. Photoluminescence (PL) analysis obtained an emission peak at ∼442 nm under the excitation wavelength of 365 for the nanocomposite, representing its blue luminescence nature. Doxorubicin (DOX) and curcumin (CUR) were co-loaded respectively, about ∼62% and ∼38% on CDs-poly(NIPAM-co-MAH)-D-Man (DOX@CUR@CDs-poly(NIPAM-co-MAH)-D-Man). The prepared system exhibited controlled drug release behavior and good biocompatibility in the in vitro cellular tests. The percentage of the arrested cells in sub G1 phase for the treated cells with DOX@CUR@CDs-poly(NIPAM-co-MAH)-D-Man was 100 %, while it was 86.85% for free DOX@CUR which can approve the high efficiency of DOX@CUR@CDs-poly(NIPAM-co-MAH)-D-Man in cancer therapy. Overall, the results displayed that the prepared nanocomposite can be potentially proposed as an efficient carrier for controlled and targeted anticancer drug delivery along with bioimaging.

Nanoemulsion carriers of porous γ-alumina modified by polyvinylpyrrolidone and carboxymethyl cellulose for pH-sensitive delivery of 5-fluorouracil

5-Fluorouracil (5-FU) is a cytotoxic drug with a low half-life. These features can cause some problems such as burst drug release and numerous side effects. In the present study, a pH-sensitive nanocomposite of polyvinylpyrrolidone (PVP)/carboxymethyl cellulose (CMC)/γ-alumina developed by using water in oil in water (W/O/W) double emulsion method. The fabricated emulsion has been employed as the 5-FU carrier to investigate its effects on drug half-life, side effects, drug loading efficiency (DLE), and drug entrapment efficiency (DEE). Analyzing the FTIR and XRD indicated the successful loading of 5-FU into the nanocarrier and affirmed the synthesized nanocomposite's chemical bonding and crystalline features. Furthermore, by using DLS and Zeta potential assessment, size and undersize distribution, as well as the stability of the drug-loaded nanocomposite were determined, which demonstrated the monodisperse and stable nanoparticles. Moreover, the nanocomposites with spherical shapes and homogeneous surfaces were shown in FE-SEM, which indicated good compatibility for the constituents of the nanocomposites. Moreover, by employing BET analysis the porosity has been investigated. Drug release pattern was studied, which indicated a controlled drug release behavior with above 96 h drug retention. Besides, the loading and entrapment efficiencies were obtained 44 % and 86 %, respectively. Furthermore, the curve fitting technique has been employed and the predominant release mechanism has been determined to evaluate the best-fitted kinetic models. MTT assay and flow cytometry assessment has been carried out to investigate the cytotoxic effects of the fabricated drug-loaded nanocomposite on MCF-7 and normal cells. The results showed enhanced cytotoxicity and late apoptosis for the PVP/CMC/γ-alumina/5-FU. Based on the MTT assay outcomes on normal cell lines (L929), which indicated above 90 % cell viability, the biocompatibility and biosafety of the synthesized nanocarrier have been confirmed. Moreover, due to the porosity of the PVP/CMC/γ-alumina, this nanocarrier can exploit from high specific surface area and be more sensitive to environmental conditions such as pH. These outcomes propose that the novel pH-sensitive PVP/CMC/γ-alumina nanocomposite can be a potential candidate for drug delivery applications, especially for cancer therapy.

HA-PEG-PCL Nanoparticles With Paclitaxel Loaded For Targeted Delivery To Colon Cancer

For improved treatment efficacy with no or few adverse effects and higher patient compliance, novel delivery techniques with selective dispersion are required. The biodegradable and biocompatible polymers hyaluronic acid (HA), polyethylene glycol (PEG), and polycaprolactone (PCL) were used to create paclitaxel-loaded nanoparticles. The development and characterisation of a Paclitaxel-loaded HA-PEG-PCL polymeric nanoparticulate drug delivery system were the goals of the current study work in order to increase the therapeutic efficacy and targeted Paclitaxel distribution. The copolymers were chemically created, and IR spectroscopies were used to identify them. Transmission electron microscopy, particle size, percentage of drug entrapment, cell viability studies, stability, and in vitro drug release profile were used to describe the nanoparticles' structure and morphology. To determine whether PTX was crystalline or amorphous inside the polymer matrix, experiments using differential scanning calorimetry and X-ray diffraction were also carried out. Zeta potentials for blank NPs and PTX-HA-PEG-PCL NPs were respectively -15.4±1.23 mV and -18±2.35 mV. In 144 hours, PTX-HA-PEG-PCL NPs demonstrated a 58.08±3.8 release of PTX at pH 7.4. Because HA functions as a ligand for the CD44 receptors that are over expressed on HT-29 cells, the PTX-HA-PEG-PCL NPs demonstrated noticeably more cytotoxicity as a result of better formulation internalization. The proposed nanotechnology’s-controlled drug release behavior showed its potential for colon cancer cell lines

A novel sulfated mannan-carboxymethyl-5-fluorouracil-folic acid conjugates for targeted anticancer drug delivery

CFP2 is a sulfated polysaccharide isolated from Codium fragile that shows excellent immunomodulatory activity. To reduce the side effects of 5-fluorouracil (5-FU), CFP2 was used as a macromolecular carrier to react with carboxymethyl-5-fluorouracil (C-5-FU) to form CFP2-C-5-FU, which further reacted with folic acid (FA) via an ester bond to form novel conjugates (CFP2-C-5-FU-FA). CFP2-C-5-FU-FA was confirmed by nuclear magnetic resonance (NMR) analysis. In vitro drug release results showed that the cumulative release rate of C-5-FU was 49.9% in phosphate buffer (pH 7.4) after 96 h, which was much higher than that of the other groups, indicating that CFP2-C-5-FU-FA showed controlled drug release behavior. CFP2-C-5-FU-FA also exhibited enhanced apoptosis and cellular uptake in vitro. Further, intravenous administration of CFP2-C-5-FU-FA in an HCT-116 cell-bearing xenograft mouse showed that the conjugates were safe and effective drug delivery systems. These results suggest that folate-targeted conjugates can be used effectively for efficient chemotherapy of colorectal cancer.

Fabrication of a Vitamin B12-Loaded Carbon Dot/Mixed-Ligand Metal Organic Framework Encapsulated within the Gelatin Microsphere for pH Sensing and In Vitro Wound Healing Assessment.

Bacterial invasion is a serious concern during the wound healing process. The colonization of bacteria is mainly responsible for the pH fluctuation at the wound site. Therefore, the fabrication of a proper wound dressing material with antibacterial activity and pH monitoring ability is necessary to acquire a fast healing process. Therefore, this work is dedicated to designing a vitamin B12-loaded gelatin microsphere (MS) decorated with a carbon dot (CD) metal-organic framework (MOF) for simultaneous pH sensing and advanced wound closure application. The resultant MS portrayed a high specific surface area and a hierarchically porous structure. Furthermore, the surface of the resultant MS contained numerous carboxyl groups and amine groups whose deprotonation and protonation with the pH alternation are accountable for the pH-sensitive properties. The vitamin B12 release study was speedy from the MOF structure in an acidic medium, which was checked by gelatin coating, and a controlled drug release behavior was observed. The system showed excellent cytocompatibility toward the L929 cell line and remarkable antibacterial performance against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Furthermore, the combined effect of Zn2+, the imidazole unit, and CDs produces an outstanding bactericidal effect on the injury sites. Finally, the in vitro wound model suggests that the presence of the vitamin B12-loaded gelatin MS accelerates the proliferation of resident fibroblast L929 cells and causes tissue regeneration in a time-dependent manner. The relative wound area, % of wound closure, and wound healing speed values are remarkable and suggest the requirement for assessing the response of the system before exploiting its prospective in vivo application.

Smart-Temporary-Film-Based Local-Delivery System with Controllable Drug-Release Behavior.

The development of a simple local drug-delivery system that exhibits the advantages of macro- and microscale carriers with controllable drug-release behavior is still highly desired. Herein, in this work, a smart temporary film was prepared from doxorubicin (DOX)-loaded shape-memory microgels via a simple hot-compression programming method. The temporary film showed a very smooth surface and easy handing, as well as macroscopy mechanical properties, which could disintegrate into the microgels with heating at 45 °C. In this case, the temporary film showed a controllable DOX release behavior when compared with the microgels, which could release the DOX on demand. Consequently, the temporary film exhibited weaker cytotoxicity to normal cells and a much longer antitumor capability, as well as a higher drug-utilization efficiency when compared with microgels. Therefore, the smart temporary film has high potential as a candidate for use as a local drug-delivery system.

A Strategy of Limited‐Space Controlled Aggregation for Generic Enhancement of Drug Loading Capability

AbstractA prevalent problem of magnetic resonance imaging (MRI) contrast agents (CAs) for drug loading applications is easy aggregation. The major concern of hollow mesoporous organosilica nanoparticles (HMONs) is hard control of untimely drug leakage. To overcome both problems, a new strategy of limited‐space controlled aggregation for generic enhancement of drug loading capability is proposed. Typically, MRI CAs of exceedingly small gadolinium oxide nanoparticle (GO) and Gd poly(acrylic acid) macrochelate (GP) are exploited to load doxorubicin (D) in HMONs hollow core. The GO@D@HMONs and GP@D@HMONs without precipitation formation display much higher drug loading contents (33.0 ± 4.9%, 39.6 ± 4.0%) than GO@D and GP@D with serious precipitation generation (4.7 ± 0.5% and 14.7 ± 3.4%), which can be ascribed to the generation of GO@D and GP@D aggregates with larger sizes in HMONs hollow core than the pore size of HMONs preventing the drug leakage. The tumor microenvironment (TME)‐specific glutathione (GSH)‐triggered degradation of HMONs and the controlled drug release behaviors reinforce the chemotherapeutic efficacy and alleviate side effects on normal cells/tissues. The GSH‐activatable T1‐MRI is favorable to high contrast tumor imaging. Overall, the strategy of limited‐space controlled aggregation is promising for generic enhancement of drug loading capability of MRI CAs, realizing MRI‐guided high‐performance cancer treatments.