Controlled Release Applications Research Articles

Designing Antibacterial-Based Quaternary Ammonium Coatings (Surfaces) or Films for Biomedical Applications: Recent Advances

Antibacterial coatings based on quaternary ammonium compounds (QACs) have been widely investigated in controlled release applications. Quaternary ammonium compounds are low-cost and easily accessible disinfectants that have been extensively used, especially after the COVID-19 outbreak. There has been a growing interest in developing a clearer understanding of various aspects that need to be taken into account for the design of quaternary ammonium compounds to be used in the biomedical field. In this contribution, we outline the mechanism of action of those materials as well as the key design parameters associated with their structure and antibacterial activity. Moreover, emphasis has been placed on the type of antibacterial coatings based on QACs and their applications in the biomedical field. A brief outlook on future research guidelines for the development of dual-function antibacterial coatings is also discussed.

Review and Future Perspectives of Stimuli-Responsive Bridged Polysilsesquioxanes in Controlled Release Applications

Bridged polysilsesquioxanes (BPSs) are emerging biomaterials composed of synergistic inorganic and organic components. These materials have been investigated as ideal carriers for therapeutic and diagnostic systems for their favorable properties, including excellent biocompatibility, physiological inertia, tunable size and morphology, and their extensive design flexibility of functional organic groups to satisfy diverse application requirements. Stimuli-responsive BPSs can be activated by both endogenous and exogenous stimuli, offering a precise, safe, and effective platform for the controlled release of various targeted therapeutics. This review aims to provide a comprehensive overview of stimuli-responsive BPSs, focusing on their synthetic strategies, biocompatibility, and biodegradability, while critically assessing their capabilities for controlled release in response to specific stimuli. Furthermore, practical suggestions and future perspectives for the design and development of BPSs are presented. This review highlights the significant role of stimuli-responsive BPSs in advancing biomedical research.

Physicochemical Characterization and Kinetics Study of Polymer Carriers with Vitamin C for Controlled Release Applications

This study focuses on the selection and evaluation of a kinetic model for the release of vitamin C from different delivery systems, including microcapsules, hydrogels, and a hybrid system combining both. The microcapsules were synthesized from a 2% sodium alginate solution and with vitamin C incorporated in selected formulations. Hydrogels were obtained through photopolymerization using poly(ethylene glycol) diacrylate and polyvinyl alcohol, with and without the addition of vitamin C. The hybrid system incorporated the vitamin C-containing microcapsules within the hydrogel matrix. Physicochemical properties, such as density, porosity, and water vapor transmission rate (WVTR), were evaluated. Kinetic studies of vitamin C release were conducted under dynamic and static conditions, and the experimental data were fitted to six different kinetic models: zero-order, first-order, second-order, Higuchi, Korsmeyer–Peppas, and Hixson–Crowell. The Higuchi and Korsmeyer–Peppas models provided the best fit for most systems, indicating that the release is predominantly controlled by diffusion and, in dynamic conditions, swelling of the matrix. The hybrid system, while exhibiting slower release than the microcapsules and hydrogel alone, demonstrated more controlled and sustained release, which is advantageous for applications requiring prolonged action.

Optimization, experimental and theoretical investigation of modified guar-gum and poly(acrylic acid) based smart hydrogel for controlled release applications in the agricultural field

A series of smart polymer hydrogels with good uptake and controlled release characteristics were synthesized free-radically by growing poly(acrylic acid) on allylated guar gum using ammonium persulfate as an initiator and trimethylolpropane triacrylate as the crosslinker. The synthesized hydrogels were evaluated using FT-IR and NMR for their structure, thermo-gravimetric analysis (TG) to measure thermal stability, and scanning electron microscopy (SEM) to analyze surface morphology and swellability by gravimetric method under different pH and temperature conditions. The soil moisture content and gel fractions were measured using gravimetric methods. Additionally, a theoretical investigation was also performed to assess the urea-holding capacity of the synthesized hydrogel matrix using density functional theory (DFT) calculations. The uptake study revealed that the hydrogel with optimized monomer feed composition absorbed 851 g/g of water, 78 % and 67 % of urea from 0.5 % and 1 % urea solutions respectively under ambient conditions. The release study showed that 56 and 47 % of absorbed urea were released over 15 days from the urea-loaded hydrogels (0.5 % and 1 % urea solutions respectively). The uptake mechanism obeyed the non-Fickian and first-order kinetics models. The experimental evaluation and DFT calculations conveyed that the synthesized hydrogel could act as a candidature matrix for the controlled release of water and fertilizer in the agricultural field.

The application of the coacervation technique for microencapsulation bioactive ingredients: A critical review

IntroductionMicrocapsules obtained from microencapsulation technology consist of an active inward kernel substance and an external layer or crust that protects and covers the kernel substance. Microencapsulation is applied in different disciplines, such as food and pharmaceutical. Coacervation, as a separator of colloidal composition into two liquid phases, is the second common method of capsulation in food industries. It provides high encapsulation efficiency and bioactive compounds-controlled liberation, may be influenced by temperature and physical and biological mechanisms, and offers desirable flexibility that patronages the development of extensive food. Reason for writingBioactive ingredients include antioxidants, vitamins, peptides, multiple unsaturated fatty acids, phytosterols, lutein, lycopene, and probiotics. Their sensitivity usually restricts the application of bioactive components. Coacervation can create a protective obstacle and optimal diffusion and compatibility characteristics in different environments. MethodologyIn this review article, the research results in the range of 2015–2024 and the useful content of related articles related to the subject were collected from various databases such as ScienceDirect and google scholar. In general, the bioactive compounds encapsulated by the microencapsulation method, especially the complex coacervation method and their advantages, the wall and core materials used, microencapsulation conditions, and finally, the results of the research are collected attractively and comprehensively. ResultsComplex coacervation could be a promising, interesting, and useful method to protect and deliver substances, such as polyunsaturated fatty acids, vitamins, antioxidants, peptides, phytosterols, lutein, lycopene, pigments and phenolic acids, enzymes, essential oils, and probiotics, for controlled release applications during storage and delivery in the gastrointestinal tract. ConclusionConsidering the advantages of bioactive components, it seems necessary to pay attention to microencapsulation methods, especially occlusion, to solve limitations in this field and to optimize the conditions and parameters of the coacervation, especially the complex coacervation.

Mannitol-Coated Hydroxypropyl Methylcellulose as a Directly Compressible Controlled Release Excipient for Moisture-Sensitive Drugs: A Stability Perspective.

Hydroxypropyl methylcellulose (HPMC) is one of the most commonly used hydrophilic polymers in formulations of matrix tablets for controlled release applications. However, HPMC attracts moisture and poses issues with drug stability in formulations containing moisture-sensitive drugs. Herein, the moisture sorption behavior of excipients and drug stability using aspirin as the model drug in matrix tablets were evaluated, using HPMC and the newly developed mannitol-coated HPMC, under accelerated stability conditions (40 °C, 75% relative humidity) with open and closed dishes. Tablets prepared with mannitol-coated HPMC showed a slower drug degradation rate compared to tablets prepared with directly compressible HPMC. Initial moisture content and hygroscopicity were stronger predictors of drug stability compared to water activity when comparing samples without similar moisture content. In the early stage (day 0 to 30), the aspirin degradation rate was similar in both open and closed conditions, as moisture content is the main degradation contributor. In the later stage (day 30 to 90), aspirin degradation was faster under closed conditions than under open conditions, likely due to autocatalytic effects caused by the volatile acidic by-product entrapped in the closed environment. The findings from this study reinforced the importance of judicious excipient selection based on the understanding of excipient-moisture interactions to maximize the chemical stability of moisture-sensitive drugs. Mannitol-coated HPMC is a promising addition to the formulator's toolbox for the formulation of controlled release dosage forms by direct compression.

Gingerol-zinc complex loaded 3D-printed calcium phosphate for controlled release application.

The therapeutic potential of natural medicines in treating bone disorders is well-established. Modifications in formulation or molecular structure can enhance their efficacy. Gingerol, an osteogenic active compound derived from ginger roots (Zingiber officinale), can form metal ion complexes. Zinc (Zn), a trace element that combats bacterial infections and promotes osteoblast proliferation, can be complexed with gingerol to form a G-Zn+2 complex. This study investigates a porous 3D-printed (3DP) calcium phosphate (CaP) scaffold loaded with the G-Zn+2 complex for drug release and cellular interactions. The scaffold is coated with polycaprolactone (PCL) to control the drug release. Diffusion-mediated kinetics results in 50% releaseof the G-Zn+2 complex over 6weeks. The G-Zn+2 complex demonstrates cytotoxicity against MG-63 osteosarcoma cells, indicated by the formation of apoptotic bodies and ruptured cell morphology on the scaffolds. G-Zn+2 PCL-coated scaffolds show a 1.2 ± 0.1-fold increase in osteoblast cell viability, and an 11.6 ± 0.5% increase in alkaline phosphatase compared to untreated scaffolds. Treated scaffolds also exhibit reduced bacterial colonization against Staphylococcus aureus bacteria, highlighting the antibacterial potential of the G-Zn+2 complex. The functionalized 3DP CaP scaffold with the G-Zn+2 complex shows significant potential for enhancing bone regeneration and preventing infections in low-load-bearing applications.

Effects of Secondary Structures and pH on the Self-Assembly of Poly(ethylene glycol)-b-polytyrosine.

Different from conventional synthetic polymers, polypeptides exhibit a distinguishing characteristic of adopting specific secondary structures, including random coils, α-helixes, and β-sheets. The conformation determines the rigidity and solubility of polypeptide chains, which further direct the self-assembly and morphology of the nanostructures. We studied the effect of distinct secondary structures on the self-assembly behavior of polytyrosine (PTyr)-derived amphiphilic copolymers. Two block copolymers of enantiopure poly(ethylene glycol)-b-poly(l-tyrosine) (PEG-b-P(l-Tyr)) and racemic poly(ethylene glycol)-b-poly(dl-tyrosine) (PEG-b-P(dl-Tyr)) were synthesized through the ring-opening polymerization of l-tyrosine N-thiocarboxyanhydride (l-Tyr-NTA) and dl-tyrosine N-thiocarboxyanhydride (dl-Tyr-NTA), respectively, by using poly(ethylene glycol) amine as the initiator. PEG44-b-P(l-Tyr)10 adopts a β-sheet conformation and self-assembles into rectangular nanosheets in aqueous solutions, while PEG44-b-P(dl-Tyr)9 is primarily in a random coil conformation with a tiny content of β-sheet structures, which self-assembles into sheaf-like nanofibrils. A pH increase results in the ionization of phenolic hydroxyl groups, which decreases the β-sheet content and increases the random coil content of the PTyr segments. Accordingly, PEG44-b-P(l-Tyr)10 and PEG44-b-P(dl-Tyr)9 self-assemble to form slender nanobelts and twisted nanoribbons, respectively, in alkaline aqueous solutions. The secondary structure-driven self-assembly of PTyr-derived copolymers is promising to construct filamentous nanostructures, which have potential for applications in controlled drug release.

Fabrication of pesticide/LDH-LAP composite assisted by zwitterionic surfactant

Using zinc-aluminum layered double hydroxides-laponite (LDH-LAP) complex as matrix, with the assistance of zwitterionic surfactants of hexadecyl dimethyl sulfobetaine (SB) and dodecyl dimethyl carboxyl betaine (DCB), the pesticides beta-cypermethrin (BCT) and imidacloprid (IMP) were inserted into the LDH-LAP to obtain BCT/SB-LDH-LAP, BCT/DCB-LDH-LAP, BCT/SB-DCB-LDH-LAP and IMP/DCB-LDH-LAP composites, respectively. Powder X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), thermogravimetric/differential thermal analysis (TGA/DTA) and scanning electron microscope (SEM) were used to characterize the structural properties of composites. BCT/SB-LDH-LAP, BCT/DCB-LDH-LAP, BCT/SB-DCB-LDH-LAP and IMP/DCB-LDH-LAP had larger interlayer distances of 4.29, 4.33, 4.33 and 4.61 nm, which were bigger than those of SB-LDH-LAP (3.87 nm), DCB-LDH-LAP (3.83 nm) and LDH-LAP (1.65 nm). The FT-IR and TGA/DTA results further confirmed the existence of SB, DCB, BCT and IMP into LDH-LAP. The pesticide releases were investigated and analyzed in pH 5.0 and 6.8 buffer solutions. The release behaviors can be fitted by pseudo second-order and parabolic diffusion models. The composites based on LDH-LAP could be suggested to potential application for controlled-release of the pesticide.

Fabrication of biocompatible water-soluble supramolecular nanofibers of oseltamivir with methyl-β-cyclodextrin for enhanced drug release

In recent times, there has been a growing interest in the advancement of nanofiber technology using materials based on cyclodextrin (CD). This heightened interest is primarily driven by their potential applications in controlled drug release. This research aims to create the nanofibers (NF) which involves incorporating an antiviral agent, oseltamivir (OTV) into the CD cavity, forming inclusion complexes (IC) that greatly improve drug encapsulation efficiency. To assess the physicochemical properties and drug-loading capabilities of these CD-based NF, a variety of characterization techniques can be utilized. It is noteworthy that NF containing OTV:MCD-IC/PVA demonstrates a continuous release of OTV (89.25%) at acidic conditions (pH 5.8) when compared to NF holding no MCD materials. Moreover, dissolution studies reveal that the resulting material is non-toxic and readily soluble in water (less than 2 min). MTT assay indicated that the examined NF are completely safe and do not have/make any adverse effects on the cells (cell viability is more than 98%). The fibroblast cells grown on nanomatrixes composed of both OTV/PVA and OTV:MCD IC/PVA NF did not display any indications of apoptosis or nuclear shrinkage. The development of such systems holds significant promise for advancing therapeutic strategies in the management of viral infections.

Exploring the Effectiveness of Carboxymethylated and Crosslinked Albizia procera Gum in Diltiazem Hydrochloride Matrix Tablets: A Comparative Analysis.

This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). Fourier Transform (FT) IR analysis affirmed polymer compatibility, while differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic interactions, while rheology examined flow and viscoelastic properties. Swelling and erosion kinetics provided insights into water penetration and stability. CAP's carboxymethyl groups (-CH2-COO-) heightened divalent cation reactivity, and crosslinking with CaCl2 produced Ca-CAP through -CH2-COO- and Ca2+ interactions. Structural similarities between the polymers were revealed by FTIR, with slight differences. DSC indicated modified thermal behavior in Ca-CAP, while Zeta potential analysis showcased negative charges, with Ca-CAP exhibiting lower negativity. XRD highlighted increased crystallinity in Ca-CAP due to calcium crosslinking. Minimal impact on RBC properties was observed with both polymers compared to the positive control as water for injection (WFI). Ca-CAP exhibited improved viscosity, strength, controlled swelling, and erosion, allowing prolonged drug release compared to CAP. Stability studies confirmed consistent six-month drug release, emphasizing Ca-CAP's potential as a stable, sustained drug delivery system over CAP. Robustness and accelerated stability tests supported these findings, underscoring the promise of Ca-CAP in controlled drug release applications.

Synthesis and real-time characterization of self-healing, injectable, fast-gelling hydrogels based on alginate multi-reducing end polysaccharides (MREPs)

Polysaccharide-based hydrogels are promising for many biomedical applications including drug delivery, wound healing, and tissue engineering. We illustrate herein self-healing, injectable, fast-gelling hydrogels prepared from multi-reducing end polysaccharides, recently introduced by the Edgar group. Simple condensation of reducing ends from multi-reducing end alginate (M-Alg) with amines from polyethylene imine (PEI) in water affords a dynamic, hydrophilic polysaccharide network. Trace amounts of acetic acid can accelerate the gelation time from hours to seconds. The fast-gelation behavior is driven by rapid Schiff base formation and strong ionic interactions induced by acetic acid. A cantilever rheometer enables real-time monitoring of changes in viscoelastic properties during hydrogel formation. The reversible nature of these crosslinks (imine bonds, ionic interactions) provides a hydrogel with low toxicity in cell studies as well as self-healing and injectable properties. Therefore, the self-healing, injectable, and fast-gelling M-Alg/PEI hydrogel holds substantial promise for biomedical, agricultural, controlled release, and other applications.

Abstract 2601: Potent antitumor activity of anti-HER2 antibody-topoisomerase I inhibitor conjugate based on self-immolative dendritic dimeric-linker

Abstract Antibody-drug conjugates (ADCs) are a rapidly expanding class of anticancer therapeutics, with 14 ADCs already approved worldwide. We developed unique linker technologies for the bioconjugation of drug molecules with controlled-release applications. We synthesized cathepsin-cleavable ADCs using a dimeric prodrug system based on a self-immolative dendritic scaffold, resulting in a high drug-antibody ratio (DAR) with the potential to reach 16 payloads due to its dendritic structure, increased stability in the circulation and efficient release profile of a highly cytotoxic payload at the targeted site. Using our novel cleavable linker technologies, we conjugated the anti-human epidermal growth factor receptor 2 (anti-HER2) antibody, trastuzumab, with topoisomerase I inhibitors, exatecan or belotecan. The newly synthesized ADCs were tested in vitro on mammary carcinoma cells overexpressing human HER2, demonstrating a substantial inhibitory effect on the proliferation of HER2-positive cells. Importantly, a single dose of our trastuzumab-based ADCs administered in vivo to mice bearing HER2-positive tumors, showed a dose-dependent inhibition of tumor growth and survival benefit, with the most potent antitumor effects observed at 10 mg/kg, which resulted in complete tumor regression and survival of 100% of the mice. Overall, our novel dendritic technologies using the protease-cleavable Val-Cit linker present an opportunity for the development of highly selective and potent controlled-released therapeutic payloads. This strategy could potentially lead to the development of novel and effective ADC technologies for patients diagnosed with HER2-positive cancers. Moreover, our proposed ADC linker technology can be implemented in additional medical conditions such as other malignancies as well as autoimmune diseases that overexpress targets, other than HER2. Citation Format: Yulia Liubomirski, Galia Tiram, Anna Scomparin, Samer Gnaim, Sayantan Das, Sachin Gholap, Liang Ge, Eilam Yeini, Omri Shelef, Arie Zauberman, Nir Berger, Doron Kalimi, Mira Toister-Achituv, Christian Schröter, Stephan Dickgiesser, Jason Tonillo, Min Shan, Carl Deutsch, Stanley Sweeney-Lasch, Doron Shabat, Ronit Satchi-Fainaro. Potent antitumor activity of anti-HER2 antibody-topoisomerase I inhibitor conjugate based on self-immolative dendritic dimeric-linker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2601.

Borophene Based 3D Extrusion Printed Nanocomposite Hydrogel for Antibacterial and Controlled Release Application

AbstractHerein, a borophene/zinc oxide (BZ) nanocomposite is synthesized through a straightforward one‐step solvothermal process, avoiding the need for any rigorous reducing agent. The BZ nanocomposites are introduced into semi‐interpenetrating polymer networks to form hydrogels via in situ UV triggered free radical gelation during three‐dimensional (3D) microextrusion printing. The hydrogels exhibit mechanical robustness, high compressibility, pH sensitivity, and microporosity. The diffusion behavior of the hydrogel shows a combination of swelling and molecular chain relaxation based on its water uptake kinetics. Hydrogels are tested in rigorous pH environments over multiple cycles to ensure structural integrity. The rheological assessment of the hydrogels proves their high elasticity. The uniaxial mechanical properties support its mechanical toughness and zero permanent set resulting elastomeric soft matrix. The cyclic compression test up to 100 cycles has negligible data deviations in calculating compression moduli (≈24 kPa). The hydrogels are non‐toxic and found to be effective bactericidal materials for both Gram‐positive and Gram‐negative bacteria. The hydrogel demonstrates pH‐responsive time‐dependent payload release behavior, suggesting its potential as a soft matrix drug carrier in biomedical research. To the best of the authors knowledge, this is the first report of BZ‐based soft biomaterial with antibacterial properties serving as an excellent controlled drug delivery device.

Potent antitumor activity of anti-HER2 antibody-topoisomerase I inhibitor conjugate based on self-immolative dendritic dimeric-linker

Antibody-drug conjugates (ADCs) are a rapidly expanding class of anticancer therapeutics, with 14 ADCs already approved worldwide. We developed unique linker technologies for the bioconjugation of drug molecules with controlled-release applications. We synthesized cathepsin-cleavable ADCs using a dimeric prodrug system based on a self-immolative dendritic scaffold, resulting in a high drug-antibody ratio (DAR) with the potential to reach 16 payloads due to its dendritic structure, increased stability in the circulation and efficient release profile of a highly cytotoxic payload at the targeted site. Using our novel cleavable linker technologies, we conjugated the anti-human epidermal growth factor receptor 2 (anti-HER2) antibody, trastuzumab, with topoisomerase I inhibitors, exatecan or belotecan. The newly synthesized ADCs were tested in vitro on mammary carcinoma cells overexpressing human HER2, demonstrating a substantial inhibitory effect on the proliferation of HER2-positive cells. Importantly, a single dose of our trastuzumab-based ADCs administered in vivo to mice bearing HER2-positive tumors, showed a dose-dependent inhibition of tumor growth and survival benefit, with the most potent antitumor effects observed at 10 mg/kg, which resulted in complete tumor regression and survival of 100% of the mice. Overall, our novel dendritic technologies using the protease-cleavable Val-Cit linker present an opportunity for the development of highly selective and potent controlled-released therapeutic payloads. This strategy could potentially lead to the development of novel and effective ADC technologies for patients diagnosed with HER2-positive cancers. Moreover, our proposed ADC linker technology can be implemented in additional medical conditions such as other malignancies as well as autoimmune diseases that overexpress targets, other than HER2.

Enhancing the Formulation of Chemically Modified Starch Bionanoparticles Through Ultrasonic Assisted Emulsification: A Parameter Study

AbstractThe design of polymeric nanoparticles has gained significant attention for drug delivery and controlled release applications. Biocompatible and degradable polyesters have emerged as promising materials for this purpose. However, achieving precise control over the size of nanoparticles (NPs) is crucial to ensure selective delivery and avoid clearance by the reticuloendothelial system. This study investigates the impact of external parameters, including polymer concentration, sonication amplitude, and sonication time, on the preparation of polymeric NPs using starch butyrate (SB) via the single emulsification‐solvent evaporation (SE‐SE) technique with ultrasound assistance. Employing a Box–Behnken method, this study optimizes the conditions for nanoformulation, obtaining response surfaces that reveal the effects of these parameters on particle size. These findings highlight that sonication time is the most influential parameter, followed by sonication amplitude and polymer concentration. By utilizing the statistical model, this study predicts and controls the variables to achieve particle diameters ranging from 152 to 346 nm. The optimal conditions for NPs preparation involve a polymer concentration of 1 mg mL−1, 40% sonication amplitude, and a 30‐min sonication time, resulting in particle sizes of 142 nm. Furthermore, this model demonstrates the capability to develop nanoformulations with excellent size homogeneity, enhancing their attractiveness and efficacy in drug delivery applications.

Charged hollow microgel capsules.

Responsive hollow microgels are a fascinating class of soft model systems at the crossover between polymer capsules and microgels. The presence of the cavity makes them promising materials for encapsulation and controlled release applications but also confers them an additional softness that is reflected by their peculiar behaviour in bulk and at interfaces. Their responsivity to external stimuli, such as temperature, pH, and ionic strength, can be designed from their synthesis conditions and the choice of functional moieties. So far most studies have focused on "small" hollow microgels that were mostly studied with scattering or atomic force microscopy techniques. In our previous study, we have shown that large fluorescent hollow poly(N-isopropylacrylamide) (PNIPAM) microgels could be synthesized using micrometer-sized silica particles as sacrificial templates allowing their investigation in situ via confocal microscopy. In this work, we extend this approach to charged large hollow microgels based on poly(N-isopropylacrylamide-co-itaconic acid) (P(NIPAM-co-IA)). Hereby, we compare the structure and responsivity of "neutral" (PNIPAM) and "charged" (P(NIPAM-co-IA)) hollow microgel systems synthesized under similar conditions with the same sacrificial template using confocal and atomic force microscopy and light scattering techniques. In particular, we could demonstrate the extremely soft character of the swollen charged hollow microgels and their responsivity to pH, ionic strength, and temperature. To conclude this study, the buckling behavior of the different capsules was investigated illustrating the potential of such systems to change its conformation by varying the osmotic pressure and pH conditions.

Preparation of a novel alginate hydrogel microspheres covered by hollow silica for controlled-release application

Sodium alginate hydrogel has been widely used in the field of controlled-release. In this paper, in order to prevent the negative effect of fast degradation and explosive release of pure sodium alginate hydrogel in the drug delivery process, we developed a novel alginate hydrogel supported by hollow silica microsphere for drug delivery. Briefly, the drugs were fused with sodium alginate and the hollow silica microspheres followed by ion crosslinking to form a composite hydrogel microsphere with a core–shell structure (SA@SiO2). The structure and morphology of the composite hydrogel were characterized by Fourier infrared spectroscopy (FT-IR), thermogravimetric analysis (TG), scanning electron microscope (SEM), transmission electron microscope (TEM) along with fluorescence microscope. On this basis, using three different types of organic compounds (rhodamine B, Indocyanine green and salicylic acid) as model molecules, the controlled-release performance of the SA@SiO2 microspheres were investigated in detail. The research results show that the drug delivery system has broad-spectrum controlled-release performance for different types of molecules, and the controlled-release time can exceed 40 h. At the same time, the pH- responsive property of the sodium alginate hydrogel endows the delivery system with a certain targeting function. This study provides a new strategy for constructing an efficient targeted drug controlled-release system.

EVALUATION OF WHEAT WITH DIFFERENT COATED CONTROLLED RELEASE UREA AND APPLICATION TIME IN SEMI-ARID CONDITIONS

Optimal nitrogen (N) application rate, source and timing are important to achieve high wheat yield. Overdose of N as basal dose promotes excessive vegetative growth and delays maturity, resulting in low N use efficiency (NUE) and crop yield. The current study was conducted for two years (2018-2019 and 2019-2020) to examine the influence of various N sources viz., common-urea, Zn-coated urea, neem-coated urea, and polymer-coated urea and their application methods (basal- and split-application) on the growth, physiology, yield, and related traits in wheat under semi-arid conditions. Results showed that N sources and application methods significantly affected the growth, physiological and yield-related traits; neem-coated urea applied in splits remained the most effective source for the observed traits, followed by Zn-coated, polymer-coated, and common urea. Compared with common urea, neem-coated urea significantly increased chlorophyll (Chl) and carotenoid contents under basal and split application. Neem-coated urea also recorded higher biological and grain yields than other
 treatments which were associated with higher values of yield-related traits including the number of productive tillers, number of spikelets, and number of grains per spike. For N application methods, split application significantly improved the plant height, Chl pigments, yield- and yield-related traits compared with the basal application. In conclusion, neem-coated urea application as a split application performed well followed by Zncoated and polymer-coated urea in improving the growth and overall yield.

Click to Self‐immolation: A “Click” Functionalization Strategy towards Triggerable Self‐Immolative Homopolymers and Block Copolymers

AbstractSelf‐immolative polymers (SIPs) are a class of degradable macromolecules that undergo stimuli‐triggered head‐to‐tail depolymerization. However, a general approach to readily end‐functionalize SIP precursors for programmed degradation remains elusive, restricting access to complex, functional SIP‐based materials. Here we present a “click to self‐immolation” strategy based on aroyl azide‐capped SIP precursors, enabling the facile construction of diverse SIPs with different trigger units through a Curtius rearrangement and alcohol/thiol‐isocyanate “click” reaction. This strategy is also applied to polymer‐polymer coupling to access fully depolymerizable block copolymer amphiphiles, even combining different SIP backbones. Our results demonstrate that the depolymerization can be actuated efficiently under physiologically‐relevant conditions by the removal of the trigger units and ensuing self‐immolation of the p‐aminobenzyl carbonate linkage, indicating promise for controlled release applications involving nanoparticles and hydrogels.