Sustained Release Applications Research Articles

Novel cinnamon essential oil-bacterial cellulose microcapsules for enhanced preservation of prefabricated meat

Bacterial cellulose, a naturally porous nanomaterial, shows significant potential in encapsulation and sustained-release applications. However, effective methods to construct bacterial cellulose microcapsules (BCM) are lacking, resulting in low embedding rates and poor slow-release effects. This study presents a novel and efficient BCM preparation strategy using mercerization to embed cinnamon essential oil (CEO). The CEO-BCM system was evaluated for its efficacy in preserving prefabricated meat. Results demonstrated that BCM, embedded with CEO through mercerization, achieved an embedding rate of 94.9 % and an average particle size of 63.7 μm. Mercerization transformed BC crystalline into cellulose type II, densifying the BCM structure, while intermolecular hydrogen bonding between BCM and CEO enhanced the stability of CEO-BCM. Release kinetics analysis indicated that CEO release was primarily diffusion-driven (Peppas-Sahlin model) with sustained release performance up to 20 days. Additionally, CEO-BCM exhibited excellent long-term antibacterial (≥81.2 % within 20 days), antioxidant, and thermal stability, effectively extending the shelf life of prefabricated meat products from 5 to 10 days. The developed BCM construction strategy not only addresses the challenges of direct BCM preparation and the limitations in core embedding and controlled release, but also enhances the stability of the CEO. This advancement further expands the application areas of bacterial cellulose (BC), and the prepared CEO-BCM system holds significant potential for food preservation applications.

A hybrid formulation of porous silicon nanoparticle with carboxymethyl cellulose for enhanced drug loading

Porous silicon nanoparticles (pSiNPs) have received considerable spotlight in drug delivery systems due to their biocompatibility, drug loading capacity, and easy surface modification. Despite these merits, the degradation rate control of pSiNPs in biological environments remains a challenge for sustained-release applications. In this study, we introduce a novel formulation of pSiNPs-based coated with carboxymethyl cellulose (pSiNPs-CMC) for the first time. The drug loading and release behavior of pSiNPs-CMC, featuring representative anticancer drugs such as doxorubicin, gemcitabine, paclitaxel, and SN-38, were extensively characterized. Notably, the CMC coating on pSiNPs resulted in an increase in loading efficiency of over 60% both for hydrophilic and hydrophobic drugs, while ensuring a controlled and tailored drug release profile. Our findings present the potential of the pSiNPs-CMC composite as a robust and versatile platform, overcoming conventional limitations in drug specificity and representing a significant advancement in sustained and personalized drug delivery systems.

An injectable, chitosan-based hydrogel prepared by Schiff base reaction for anti-bacterial and sustained release applications

Injectable hydrogels, providing sustained release as implanted materials, have received tremendous attention. In this study, chitosan-based hydrogels were prepared via Schiff base reaction of the aldehyde groups on Poly(NIPAM-co-FBEMA) and the amine groups on chitosan. Owing to the dynamic covalent linkage, the SC/PNF hydrogels exhibit pH-responsive, reversible sol-gel transition, injectable, and self-healing capacity. The mechanical strength of SC/PNF hydrogels can be operated simply by switching the composition or solid content of Poly(NIPAM-co-FBEMA) copolymers. Rheological analyses, including frequency sweeps, strain sweep scanning, and dynamic time sweeps, were employed to demonstrate the relationship between storage modulus (G′), loss modulus (G″), and composition of the SC/PNF hydrogels. In vitro release behaviors reveal that vancomycin-loaded SC/PNF hydrogel could contribute to both the initial burst release (over 1000 ppm within 4 h) and the sustained release (3000 ppm for at least 30 days). Pristine SC/PNF hydrogel holds good biocompatibility toward L929 cells and S. aureus that it degrades as incubated with S. aureus. However, vancomycin-wrapped SC/PNF hydrogel possesses a rapid bacterial-killing effect with a clear inhibition zone. In short, the SC/PNF hydrogels deliver not only sustainable release ability but also tunable physical properties, which are expected to be an outstanding candidate for non-invasive, anti-infection applications.

Synthesis, characterization of poly l(+) lactic acid and its application in sustained release of isosorbide dinitrate

Poly l(+) lactic acid (PLLA) has become crucial in the biomedical industry for various uses. The direct polycondensation method was used to prepare Poly l(+) Lactic Acid (PLLA). Different catalysts, including metal oxides and metal halides, were used to test the polymerization technique. The effect of the amount of catalysts and the type of coupling agent were investigated. The effect of reaction time and polymerization solvents was also studied. PLLA was loaded with isosorbide dinitrate utilizing the solvent evaporation process. The synthesized polymer-drug system was evaluated by different means such as FT-IR, TGA, DSC, XRD, entrapment efficiency (E.E), drug loading (D.L), particle size analysis, and zeta potential determination. Studies on in-vitro release using UV light at 227 nm at various pH levels were conducted, and the kinetics of release and cytotoxicity using the sulforhodamine B (SRB) assay on human skin fibroblast cells were examined.

Nanoparticle‐based sustained drug delivery for the treatment of ocular neovascular diseases

Aims/Purpose: Nanoparticles have shown great potential as a drug delivery system for the treatment of neovascular ocular diseases characterized by the growth of abnormal blood vessels in the retina. The current standard of therapy for neovascular ocular diseases involves administering monoclonal antibody‐based anti‐VEGF drugs via intravitreal injections on a periodic basis. The short half‐lives of these drugs necessitate frequent injections, which can limit the effectiveness of the treatments. Hence, there is a need to develop new approaches for enhanced bioavailability and sustained and long‐lasting delivery of anti‐VEGF drugs. The aim of this study was to utilize poly (glycerol sebacate) (PGS) nanoparticles to achieve an extended release of anti‐VEGF (anti‐vascular endothelial growth factor) drugs, with the objective of reducing the frequency of intravitreal injections required for treatment.Methods: Double emulsion solvent evaporation method was utilized for the synthesis of PGS nanoparticles. Nanoparticle size and polydispersity index (PDI) were determined with dynamic light scattering method.Results: Nanoparticles were synthesized with a size of approximately 150 nm and PDI less than 0.3. The encapsulation efficiency of nanoparticles loaded with anti‐VEGF drugs was found to be 74%. The 30% drug release from nanoparticles in the first 2 months indicates that nanoparticles are a promising candidate for sustained drug release applications. Cell‐viability studies showed that anti‐VEGF drug‐loaded nanoparticles did not exhibit toxicity to ARPE‐19 cells, but they did exhibit anti‐angiogenesis properties by inhibiting the growth of HUVEC cells in a concentration‐dependent manner.Conclusions: The development of new‐generation materials for the storage and preservation of anti‐VEGF drugs, as well as their enhancement with prolonged release, will considerably improve the efficacy of long‐term treatment strategies for ocular neovascular diseases.

Citric acid cross-linking of a hydrogel from Aloe vera (Aloe barbadensis M.) engenders a pH-responsive, superporous, and smart material for drug delivery.

The current research work is based on the evaluation of a citric acid (CA) cross-linked Aloe vera (Aloe barbadensis M.) leaf hydrogel (CL-ALH) for pH-dependent and sustained drug release application. The CA was used in different concentrations (1.25, 2.5, 5.0, and 10.0%) to cross-link the ALH using homogenous reaction conditions. The synthesis of CL-ALH was confirmed through Fourier transform and nuclear magnetic resonance spectroscopic studies. The thermal analysis indicated that the ALH and CL-ALH were stable and decomposed in two steps. The scanning electron microscopic images of CL-ALH confirmed its porous nature due to the presence of interconnected channeling. The swelling of CL-ALH was evaluated at pH 1.2, 6.8, and 7.4 as well as in deionized water (DW). High swelling of CL-ALH was observed in DW, and at pH 7.4 and 6.8 whereas, less swelling of CL-ALH was witnessed at pH 1.2. CL-ALH also exhibited swelling/deswelling behavior in DW and ethanol, DW and normal saline, and at pH 7.4 and 1.2. Tablets were prepared from CL-ALH as a release retarding agent demonstrating the sustained release of venlafaxine hydrochloride (VFX) for 8 h. Whereas, VFX was released within 4 h from the ALH-based tablet formulation (un-cross-linked material) indicating the prolonged and sustained release behavior of CL-ALH. The VFX was released from CL-ALH tablets and followed zero-order kinetics. The mechanism followed by VFX release from CL-ALH tablets was non-Fickian diffusion. The in vivo fate of the tablet formulation was observed through an X-ray study. The CL-ALH-based tablet safely passed through the stomach of a stray dog without any significant erosion and then disintegrated in the small intestine and colon. These findings confirmed that the CL-ALH is an effective excipient for designing a sustained-release drug delivery system for the small intestine and colon.

Multiparticulate Drug Delivery of Losartan Potassium via Extrusion-Spheronization: Formulation and Dissolution Comparisons

Abstract Background: Losartan potassium, an antihypertensive medication, has high solubility and a short half-life that result in potential adverse effects and rapid drug clearance. Multiparticulate drug delivery systems enhance the drug’s bioavailability, decrease patient-to-patient variability, and optimize drug distribution. Herein, losartan potassium pellets for sustained drug release were developed and characterized. Methods: The formulation process involved varying the concentrations of Eudragit RSPO (200 mg, 400 mg, or 600 mg) and Eudragit L100 (200 mg, 400 mg, or 600 mg) across nine pellet batches, and adjusting the triethyl citrate concentrations accordingly. The pellets’ bulk density, tapped density, flow properties (Carr’s index, Hausner’s ratio, and angle of repose), drug content, particle size distribution, and in vitro drug release were evaluated. Interactions between losartan potassium and the excipients were analyzed with FTIR and DSC. Results: FTIR spectra indicated physical interactions without major chemical alterations, whereas DSC thermograms revealed changes in thermal behavior due to excipient interactions. In vitro drug release studies indicated that formulations with higher concentrations of Eudragit RSPO and triethyl citrate achieved controlled, prolonged drug release. The optimized batch (F7) demonstrated balanced characteristics including favorable bulk and tapped density, good flow properties, and a sustained release profile. Varying the polymer and plasticizer concentrations significantly influenced pellet performance, and F7 was found to be the most promising formulation for sustained-release applications. Conclusion: This study underscores the importance of polymer selection and formulation optimization in developing effective sustained-release drug delivery systems, and has potential implications for enhancing therapeutic outcomes in clinical practice.

Accelerated self-assembly of filipin proteins and formation of hydrogels

This study delineates the novel revelation that traditional Chinese medicine polysaccharides facilitate and expedite the intramolecular conformational alterations within filipin proteins, culminating in amplified β-fold content and self-assembly proclivity to generate hydrogels. Augmentation of assembly kinetics was achieved by pH or ethanol supplementation. The resultant self-assembled hydrogels exhibited homogenous pore size distribution, registering porosities consistently surpassing 95 ± 2.3%, effectively accommodating pharmaceutical payloads. Noteworthy characteristics included low water loss rates spanning between 15% and 25%, exceptional swelling behavior, a storage modulus (G') ranging from 68 to 283 Pa, and discernible mechanical robustness. Insights into the self-assembly mechanism were preliminarily explained via Fourier infrared, Raman spectroscopy and X-ray diffraction spectroscopy analyses. In-depth examinations, encompassing in-vitro release, degradation and biocompatibility, corroborated the hydrogel’s capacity for smooth drug release, sustained stability, absence of cytotoxicity and favorable biocompatibility. In conclusion, the self-assembled filipin protein hydrogels preserved polysaccharide activity to a heightened extent and enhanced drug adaptability by reducing the overall formulation volume. This innovation, we suggest, holds significant promise for applications in sustained drug release and in the realm of tissue engineering materials.

The Application of Response Surface Methodology (RSM) In the Computational Optimization of Sustained Release (SR) For Phenothiazine Derivative Matrix Tablet

Introduction: This study explores the use of Response Surface Methodology (RSM), a statistical optimization technique, to optimize the SR properties of prochlorperazine maleate (PCM) matrix tablets. PCM is a phenothiazine derivative used for treating schizophrenia, nausea, and vomiting. Sustained-release formulations offer extended drug delivery, potentially improving patient compliance and reducing side effects. RSM helps identify optimal combinations of critical formulation factors influencing drug release, such as polymer type and concentration, filler type, and drug/polymer ratio. The study likely involves designing experiments based on chosen RSM designs (e.g., Box-Behnken) with varying factor levels. Formulate SR tablets with different factor combinations. Evaluating the drug release profiles of each tablet formulation. Analyzing data using RSM software to build mathematical models relating factors to drug release and identifying optimal factor combinations that maximize desired release characteristics. Objective: The ongoing research purpose to improve the advancement of a sustained release tablet containing Phenothiazine derivative PCM loaded matrix. This is achieved by utilizing DoE as a computational method to statistically validate the formulation. Methodology: Basically two methods involved in the formulation using direct compression; a simple and efficient method where all dry ingredients are blended and directly compressed into tablets. Results: The obtained outcomes closely matched the anticipated values derived from the experimental setup. The enhanced PCM matrix tablets demonstrated a prolonged and uniform discharge of PCM over a span of 6 hours. Conclusion: This study Based on a 23 FD, response surface methodology was used to successfully develop the current research of PCM matrix tablets for sustained release application. The corresponding contour plots and 3D response methodology represent the important variables for the optimisation process.

Synthesis and characterization of zinc ion-integrated quercetin delivery system using areca nut seeds nanocellulose

This research introduces an innovative approach utilizing waste-derived cellulose from areca nut seeds. A novel quercetin-loaded cellulose nanofiber (CNF-Zn-QT) composite was synthesized by integrating zinc ions into a cellulose nanofiber-quercetin complex. With a high loading capacity (17.48%) and encapsulation efficiency (90.42%), the optimized CNF-Zn-QT composite exhibited superior antioxidant activity against DPPH and ABTS+ radicals compared to quercetin alone. Furthermore, the CNF-Zn-QT composite demonstrated a slower in vitro release rate of quercetin, indicating its potential for sustained release applications. Notably, the composite also displayed enhanced antibacterial properties, attributed to the antibacterial nature of zinc ions. In terms of storage, the CNF-Zn-QT composite outperformed the CNF-QT composite in stability, underscoring its promise for long-term applications. This research not only offers a novel perspective on the utilization of areca nut seeds waste but also emphasizes the multifunctional capabilities of the CNF-Zn-QT composite, making it a promising candidate for various applications, including antioxidant and antibacterial products, controlled release systems, and stable storage solutions.

Citric acid crosslinked biocompatible silk fibroin-mediated porous chitosan films for sustained drug release application

Citric acid crosslinked biocompatible silk fibroin-mediated porous chitosan films for sustained drug release application

Accelerating Payload Release from Complex Coacervates through Mechanical Stimulation.

Complex coacervates formed through the association of charged polymers with oppositely charged species are often investigated for controlled release applications and can provide highly sustained (multi-day, -week or -month) release of both small-molecule and macromolecular actives. This release, however, can sometimes be too slow to deliver the active molecules in the doses needed to achieve the desired effect. Here, we explore how the slow release of small molecules from coacervate matrices can be accelerated through mechanical stimulation. Using coacervates formed through the association of poly(allylamine hydrochloride) (PAH) with pentavalent tripolyphosphate (TPP) ions and Rhodamine B dye as the model coacervate and payload, we demonstrate that slow payload release from complex coacervates can be accelerated severalfold through mechanical stimulation (akin to flavor release from a chewed piece of gum). The stimulation leading to this effect can be readily achieved through either perforation (with needles) or compression of the coacervates and, besides accelerating the release, can result in a deswelling of the coacervate phases. The mechanical activation effect evidently reflects the rupture and collapse of solvent-filled pores, which form due to osmotic swelling of the solute-charged coacervate pellets and is most pronounced in release media that favor swelling. This stimulation effect is therefore strong in deionized water (where the swelling is substantial) and only subtle and shorter-lived in phosphate buffered saline (where the PAH/TPP coacervate swelling is inhibited). Taken together, these findings suggest that mechanical activation could be useful in extending the complex coacervate matrix efficacy in highly sustained release applications where the slowly releasing coacervate-based sustained release vehicles undergo significant osmotic swelling.

Nanomedicine and versatile therapies for cancer treatment.

The higher prevalence of cancer is related to high rates of mortality and morbidity worldwide. By virtue of the properties of matter at the nanoscale, nanomedicine is proven to be a powerful tool to develop innovative drug carriers with greater efficacies and fewer side effects than conventional therapies. In this review, different nanocarriers for controlled drug release and their routes of administration have been discussed in detail, especially for cancer treatment. Special emphasis has been given on the design of drug delivery vehicles for sustained release and specific application methods for targeted delivery to the affected areas. Different polymeric vehicles designed for the delivery of chemotherapeutics have been discussed, including graft copolymers, liposomes, hydrogels, dendrimers, micelles, and nanoparticles. Furthermore, the effect of dimensional properties on chemotherapy is vividly described. Another integral section of the review focuses on the modes of administration of nanomedicines and emerging therapies, such as photothermal, photodynamic, immunotherapy, chemodynamic, and gas therapy, for cancer treatment. The properties, therapeutic value, advantages, and limitations of these nanomedicines are highlighted, with a focus on their increased performance versus conventional molecular anticancer therapies.

Preparation of Nanostructured Graphene Oxide and Its Application in Drug Loading and Sustained Release

Nanostructured graphene oxide (GO) with long-range ordered lamellar or hexagonal structure were prepared by lyotropic liquid crystals (LLCs) templating strategy and used as anticancer drug carriers.

Fabrication of phenylalanine amidated pectin using ultra-low temperature enzymatic method and its hydrogel properties in drug sustained release application

In this study, pectin was modified with phenylalanine by ultra-low temperature enzymatic method to improve its gel properties. The grafting ratio of phenylalanine amidated pectin was studied under different reaction conditions. The highest value (29.21 %) was reached a reaction temperature of −5 °C and time of 12 h. Further analysis indicated that phenylalanine and high methoxyl pectin combined at the solid-liquid two phase interface under the catalysis of papain to form phenylalanine amidated pectin. Moreover, the physicochemical properties of pectin hydrogel and its feasibility as a sustained-release drug carrier were discussed. The results showed that phenylalanine amidated pectin can form hydrogel with a certain strength under acidic conditions, and there is no need to add a lot of soluble solids and divalent cations. Besides, the phenylalanine amidated pectin hydrogel as a sustained release carrier of drugs showed more sustained and complete drug release.

Green starch/graphene oxide hydrogel nanocomposites for sustained release applications

Green nanocomposite hydrogels (ST-PHEMA/GO) comprised of starch and 2-Hydroxyethyl methacrylate (HEMA) reinforced with different ratios of graphene oxide (GO) were prepared via gamma radiation induced crosslinking polymerization. The chemical structure and morphology and the crystallinity were studied by FTIR FE-SEM, AFM, TEM and XRD, respectively. The swelling behavior of the claimed hydrogels was verified versus time and the pH-dependent swelling at three different irradiation dose:10, 20 and 30 kGy was also investigated. The results of the swelling study showed that the swelling capacity of the hydrogel networks varied with the changes of the pH of the solution, the GO content and the irradiation doses. Moreover, the swelling isotherm of all the prepared hydrogels followed a Fickian diffusion mechanism n < 0.5.Graphical abstract

Fabrication of Multi-Layered Microspheres Based on Phase Separation for Drug Delivery.

In this work, we used a co-flow microfluidic device with an injection and a collection tube to generate droplets with different layers due to phase separation. The phase separation system consisted of poly(ethylene glycol) diacrylate 700 (PEGDA 700), PEGDA 250, and sodium alginate aqueous solution. When the mixture droplets formed in the outer phase, PEGDA 700 in the droplets would transfer into the outer aqueous solution, while PEGDA 250 still stayed in the initial droplet, breaking the miscibility equilibrium of the mixture and triggering the phase separation. As the phase separation proceeded, new cores emerged in the droplets, gradually forming the second and third layers. Emulsion droplets with different layers were polymerized under ultraviolet (UV) irradiation at different stages of phase separation to obtain microspheres. Microspheres with different layers showed various release behaviors in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The release rate decreased with the increase in the number of layers, which showed a potential application in sustained drug release.

Tailor made magnetic nanolights: fabrication to cancer theranostics applications.

Nanoparticles having magnetic and fluorescent properties could be considered as a gift to materials scientists due to their unique magneto-optical qualities. Multiple component particles can overcome challenges related with a single component and unveil bifunctional/multifunctional features that can enlarge their applications in diagnostic imaging agents and therapeutic delivery vehicles. Bifunctional nanoparticles that have both luminescent and magnetic features are termed as magnetic nanolights. Herein, we present recent progress of magneto-fluorescent nanoparticles (quantum dots based magnetic nanoparticles, Janus particles, and heterocrystalline fluorescent magnetic materials), comprehensively describing fabrication strategies, types, and biomedical applications. In this review, our aim is not only to encompass the preparation strategies of these special types of magneto-fluorescent nanomaterials but also their extensive applications in bioimaging techniques, cancer therapy (targeted and hyperthermic), and sustained release of active agents (drugs, proteins, antibodies, hormones, enzymes, growth factors).

Hollow Microcapsules Through Layer-by-Layer Self-Assembly of Chitosan/Alginate on E. coli

Hollow microcapsules prepared via layer-by-layer (LbL) self-assembled polyelectrolytes are prevalent biomaterials in the synthesis of biocompatible delivery systems for drugs, imaging probes, and other macromolecules to control biodistribution and lower toxicity in vivo. The use of LbL self-assembly for the synthesis of these capsules provides several benefits including ease of fabrication, abundance in choice of substrates and coating material, as well as application-specific tunability. This study explores the development of hollow microcapsules by LbL assembly of chitosan and alginate onto live E. coli cells, and also provides a proof-of-concept of this capsule as a delivery platform through the encapsulation of quantum dots as a cargo. The study found that robust bilayers of chitosan/alginate can be formed onto the core substrate (E. coli) containing quantum dots as demonstrated with zeta potential analysis. Confocal microscopy was used to verify cell viability and the internalization of quantum dots into the cells as well as confirmation of the coating using fluorescein-labelled chitosan. Furthermore, transmission electron microscopy (TEM) was used to analyse cells coated with four-bilayers and showed a uniform coating morphology with a capsule thickness of 10-20 nm, which increased to 20- 50 nm for hollow capsules after cell lysis. Quantum dot retention in the capsules was demonstrated using fluorescence measurements. Overall, the study shows promising results of a novel fabrication method for hollow microcapsules that uses biocompatible polymers and mild core dissolution conditions using cell templates with applications in sustained release of therapeutics and imaging probes.

Sustained drug release and bactericidal activity of a novel, highly biocompatible and biodegradable polymer nanocomposite loaded with norfloxacin for potential use in antibacterial therapy

In this study, novel poly(3-hydroxybutyrate) (PHB) based Calcium–Iron Layered Double Hydroxide (Ca–Fe LDH) nanocomposites were investigated for sustained drug delivery application using the antibiotic norflaxacin (NFX) as a model drug. Compared with other LDH and montmorillonite nanoclays, Ca–Fe LDH showed a high drug loading capacity. In vitro drug release experiments with PHB/NFX, PHB/NFX LDH, and PHB/PEG/NFX LDH were performed using two different phosphate buffer solutions of pH 5.3 and pH 7.4. Among these nanocomposites, the PHB/PEG/3 NFX LDH nanocomposite showed a very high drug release efficiency of 95.91% in pH 5.3 and 73.40 ± 3.41% in pH 7.4, which was followed by PHB/3 NFX LDH with a drug release efficiency of 82.60% in pH 5.3 and 66.81 ± 2.25% in pH 7.4. Furthermore, the drug release kinetics due to PHB/PEG/3 NFX LDH in pH 5.3 and pH 7.4 followed zero-order and Higuchi model kinetics, respectively. Characterization results of the polymer nanocomposite films using x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FETEM) and field emission scanning electron microscopy (FESEM) analysis as well as antibacterial activity of the PHB formulations against Staphylococcus aureus and Escherichia coli revealed excellent potential of the PHB based LDH nanocomposites for sustained drug release applications.