Controlled Drug Release Behavior Research Articles

Dynamic Boronate Ester Based Hydrogel with Enhanced Mechanical Properties and Multi-Stimuli-Triggered Release for Tissue Repair and Antioxidant Therapy.

Oxidative stress and chronic inflammation play pivotal roles in causing impaired tissue regeneration and delaying wound healing processes. Epigallocatechin gallate (EGCG) demonstrates robust anti-inflammatory and antioxidant characteristics, thereby emerging as a highly promising therapeutic substance for tissue repair applications. In order to counteract the pathological characteristics of the wound microenvironment, including increased levels of reactive oxygen species (ROS), low pH (weak acidic conditions), and elevated glucose concentrations, a hydrogel with pH/ROS/glucose-responsive properties was fabricated. This hydrogel was modified with phenylboronic acid (PBA) groups, which not only enhance its mechanical strength but also endow it with multi-stimuli responsiveness via dynamic boronate ester bonds. The impacts of grafting of PBA and loading of EGCG on the rheological and mechanical properties, as well as the network structure of the hydrogels, were systematically investigated. Moreover, in vitro experiments showed that the hydrogel could achieve excellent sustained and controlled release of both small-molecule and macromolecular drugs. Additionally, cell viability tests verified the hydrogel's outstanding biocompatibility, and antioxidant experiments demonstrated its efficient ability to scavenge intracellular ROS. In conclusion, this injectable and biodegradable hydrogel possesses multi-stimuli responsiveness, controllable drug release behavior, and antioxidant capacity, presenting a promising approach to alleviate oxidative damage and promote tissue repair. This study offers valuable perspectives for the design of advanced hydrogel materials aimed at treating wound healing.

Beta‐glucan modification and incorporation of peptide for infected wound healing applications

Abstract Hydrogel dressings, known for their breathability and hygroscopic properties, have garnered significant attention in the field of bioactive wound care. Among them, hydrogels composed of polysaccharides and peptides offer superior biocompatibility, intrinsic antibacterial properties, and the ability to mimic the extracellular matrix. In this study, we developed hybrid hydrogels, BAA/C8G2, BAA/G3, and BAA/c(KW), by crosslinking immunomodulatory β‐glucan derivatives with antimicrobial peptides via enamine bonds. These hydrogels exhibited enhanced mechanical strength compared to those crosslinked with oxidized β‐glucan through imine bonding, alongside pH responsiveness and controlled drug release behavior. The hydrogels demonstrate broad‐spectrum antibacterial activity against both Gram‐positive and Gram‐negative bacteria, including methicillin‐resistant Staphylococcus aureus (MRSA), and maintain sustained inhibition of Escherichia coli for over 10 days. Furthermore, they displayed excellent in vitro biocompatibility and effectively promoted fibroblast cell migration. The results highlight the potential of enamine‐linked polysaccharide–peptide hybrid hydrogels as promising candidates for bacterial‐infected wound treatment.Highlights Acetoacetyl β‐glucan crosslinked with AMPs via dynamic enamine bonds. The BAA‐peptide hydrogels demonstrated improved mechanical properties. The pH‐responsive enamine bonds enabled controlled release of AMPs. The hydrogels exhibited sustained antibacterial activity. The hydrogels are biocompatible and promote cell migration.

Catalyst Improved Stereoselectivity and Regioselectivity Control to Access Completely Alternating Poly(lactic-co-glycolic acid) with Enhanced Properties.

The poly(lactic-co-glycolic acid) (PLGA) with completely alternating sequence has attracted growing attention as an ideal candidate in controlled drug delivery. However, the approach to completely alternating PLGA remains a challenge. Herein, we report the successful synthesis of completely alternating PLGA via highly regioselective and stereoselective ring-opening polymerization. The chiral (BisSalen)Al catalyst promoted a robust polymerization of enantiopure 3-methyl glycolide (MeG) with highly glycolyl site selectivity, affording alternating PLGA with regioselectivity up to more than 99 %. Impressively, the completely alternating PLGA exhibited a well-defined melting temperature Tm of 143.1 °C. Moreover, a stereocomplex between PLLGA and PDLGA was also formed with the improved Tm of 211.8 °C. The In vitro degradation and drug release experiments revealed the linear degradation and controlled drug release behavior of completely alternating PLGA, which can be used as an ideal carrier for mild long-acting drug delivery. Meanwhile, the reason of the high regioselectivity was investigated through the control experiments and DFT calculation. This highly regioselective (BisSalen)Al catalyst opens a door to providing completely alternating polymers.

Catalyst Improved Stereoselectivity and Regioselectivity Control to Access Completely Alternating Poly(lactic‐co‐glycolic acid) with Enhanced Properties

The poly(lactic‐co‐glycolic acid) (PLGA) with completely alternating sequence has attracted growing attention as an ideal candidate in controlled drug delivery. However, the approach to completely alternating PLGA remains a challenge. Herein, we report the successful synthesis of completely alternating PLGA via highly regioselective and stereoselective ring‐opening polymerization. The chiral (BisSalen)Al catalyst promoted a robust polymerization of enantiopure 3‐methyl glycolide (MeG) with highly glycolic site selectivity, affording alternating PLGA with regioselectivity up to more than 99%. Impressively, the completely alternating PLGA exhibited a well‐defined melting temperature Tm of 143.1 °C. Moreover, a stereocomplex between PLLGA and PDLGA was also formed with the improved Tm of 211.8 °C. The In vitro degradation and drug release experiments revealed the linear degradation and controlled drug release behavior of completely alternating PLGA, which can be used as an ideal carrier for mild long‐acting drug delivery. Meanwhile, the reason of the high regioselectivity was investigated through the control experiments and DFT calculation. This highly regioselective (BisSalen)Al catalyst opens a door to providing completely alternating polymers.

In situ growth of ZIF-8 on cellulose microspheres with high doxorubicin loading capacity and pH-sensitive for oral drug delivery

In situ growth of ZIF-8 on cellulose microspheres with high doxorubicin loading capacity and pH-sensitive for oral drug delivery

Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid‐Coated Coordination Polymer Nanoparticles

The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin‐based chemotherapy is the first‐line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt‐COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt‐COOH, and Gossypol from HA@PFG NPs. Pt‐COOH with GSH consumption and cisplatin‐based chemotherapy plus Gossypol with pro‐apoptotic effects displays a synergistic effect for killing tumor cells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. In the patient‐derived tumor xenograft (PDX) model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL‐6 signal pathways. This work combines MRI imaging with cisplatin‐based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.

Sodium ampicillin release from biocompatible hydrogel with enhanced antibacterial characteristics

Sodium ampicillin release from biocompatible hydrogel with enhanced antibacterial characteristics

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

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

Preparation of novel sulfated polysaccharide-carboxymethyl-5-fluorouracil-folic acid conjugates for targeted anticancer drug delivery

Preparation of novel sulfated polysaccharide-carboxymethyl-5-fluorouracil-folic acid conjugates for targeted anticancer drug delivery

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

Abstract Chitosan (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.

Empowering Cartilage Restructuring with Biodegradable Magnesium Doped-Silicon Based-Nanoplatforms: Sustained Delivery and Enhanced Differentiation Potential

BackgroundCartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines.MethodsA biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed. Briefly, the MON was modified with sulfhydryl groups using MPTMS to form MOS. Further engineering of MOS was achieved by incorporating Mg2+ ions through the “dissolution-regrowth” method, resulting in MMOS. Ica was effectively loaded into the MMOS channels, and HA was anchored on the surface of MOS to obtain MMOS-Ica@HA nanoplatforms. Additionally, in vitro cell experiments and in vivo zebrafish embryo models were used to evaluate the effect of the nanoplatforms on cartilage differentiation or formation and the efficiency of treating chondrodysplasia.ResultsA series of characterization tests including TEM, SEM, DLS, XPS, EDX, and BET analysis validate the successful preparation of MOS-Ica@HA nanoplatforms. The prepared nanoplatforms show excellent dispersion and controllable drug release behavior. The cytotoxicity evaluation reveals the good biocompatibility of MOS-Ica@HA due to the sustained and controllable release of Ica. Importantly, the presence of Ica and Mg component in MOS-Ica@HA significantly promote chondrogenic differentiation of BMSCs via the Smad5/HIF-1α signaling pathway. In vitro and in vivo experiments confirmed that the nanoplatforms improved chondrodysplasia by promoting cartilage differentiation and formation.ConclusionThe findings suggest the potential application of the developed biodegradable MMOS-Ica@HA nanoplatforms with acceptable drug loading capacity and controlled drug release in chondrodysplasia treatment, which indicates a promising approach for the treatment of chondrodysplasia.

Controllable rheological properties of UV-responsive calix[4]arene gel for drug encapsulation and release.

This study investigates the potential of calix[4]arene-based supramolecular gels for use in drug delivery systems, focusing on both their rheological properties and controlled drug release behavior. We explore how key factors, including temperature, solvent exchange, and UV exposure, influence the gel's mechanical strength and its ability to encapsulate and release drugs. Specifically, our work examines how these external stimuli affect the stability of the gel matrix and modulate the release rate of the encapsulated drug. By systematically evaluating the effects of each factor, we aim to identify conditions that optimize drug release kinetics. The findings offer valuable insights into the development of a tunable, responsive platform for efficient drug delivery, highlighting the potential of calix[4]arene gels as promising candidates for advanced therapeutic applications.

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.