Controlled-release Delivery System Research Articles

Effect of inulin on structural, physicochemical, and in vitro gastrointestinal tract release properties of core-shell hydrogel beads as a delivery system for vitamin B12

In this study, core-shell hydrogel beads were developed as a controlled-release delivery system for vitamin B12. Vitamin B12-loaded microgels (MG) were prepared using gellan gum (GG). Core-shell hydrogel beads were produced by incorporating MG into pea protein isolate (PPI) and sodium alginate (AL) matrix filled/coated with different concentrations (0 %, 1 %, 3 %, 5 %, and 10 %) of inulin (IN). Based on XRD analysis, MG was successfully incorporated into core-shell hydrogel beads. In FE-SEM and FT-IR analyses, the smoother surface and denser structure of the beads were observed as IN concentration increased due to hydrogen bonds between IN and the beads. The encapsulation efficiency increased from 68.64 % to 82.36 % as IN concentration increased from 0 % to 10 %, respectively. After exposure to simulated oral and gastric conditions, core-shell hydrogel beads exhibited a lower cumulative release than MG, and a more sustained release was observed as IN concentration increased in simulated intestinal conditions.

Development of a local controlled release system for therapeutic proteins in the treatment of skeletal muscle injuries and diseases

The present study aims to develop and characterize a controlled-release delivery system for protein therapeutics in skeletal muscle regeneration following an acute injury. The therapeutic protein, a membrane-GPI anchored protein called Cripto, was immobilized in an injectable hydrogel delivery vehicle for local administration and sustained release. The hydrogel was made of poly(ethylene glycol)-fibrinogen (PEG-Fibrinogen, PF), in the form of injectable microspheres. The PF microspheres exhibited a spherical morphology with an average diameter of approximately 100 micrometers, and the Cripto protein was uniformly entrapped within them. The release rate of Cripto from the PF microspheres was controlled by tuning the crosslinking density of the hydrogel, which was varied by changing the concentration of poly(ethylene glycol) diacrylate (PEG-DA) crosslinker. In vitro experiments confirmed a sustained-release profile of Cripto from the PF microspheres for up to 27 days. The released Cripto was biologically active and promoted the in vitro proliferation of mouse myoblasts. The therapeutic effect of PF-mediated delivery of Cripto in vivo was tested in a cardiotoxin (CTX)-induced muscle injury model in mice. The Cripto caused an increase in the in vivo expression of the myogenic markers Pax7, the differentiation makers eMHC and Desmin, higher numbers of centro-nucleated myofibers and greater areas of regenerated muscle tissue. Collectively, these results establish the PF microspheres as a potential delivery system for the localized, sustained release of therapeutic proteins toward the accelerated repair of damaged muscle tissue following acute injuries.

Synthesis and characterization of ion-induced sodium alginate/soy protein isolate microgels for the controlled release

In this study, sodium alginate/ soy protein isolate (SPI) microgels cross-linked by various divalent cations including Cu2+, Ba2+, Ca2+, and Zn2+ were fabricated. Cryo-scanning electron microscopy observations revealed distinctive structural variations among the microgels. In the context of gastric pH conditions, the degree of shrinkage of the microgels followed the sequence of Ca2+ > Ba2+ > Cu2+ > Zn2+. Meanwhile, under intestinal pH conditions, the degree of swelling was ranked as Zn2+ > Ca2+ > Ba2+ > Cu2+. The impact of these variations was investigated through in vitro digestion studies, revealing that all microgels successfully delayed the release of β-carotene within the stomach. Within the simulated intestinal fluid, the microgel cross-linked with Zn2+ exhibited an initial burst release, while those cross-linked with Cu2+, Ba2+, or Ca2+ displayed a sustained release pattern. This research underscores the potential of sodium alginate/SPI microgels cross-linked with different divalent cations as efficient controlled-release delivery systems.

Sustained adenosine release: Revealing its impact on osteogenic signalling pathways of human mesenchymal stromal cells

Non-healing fractures, a global health concern arising from trauma, osteoporosis, and tumours, can lead to severe disabilities. Adenosine, integral to cellular energy metabolism, gains prominence in bone regeneration via adenosine A2B receptor activation. This study introduces a controlled-release system for localized adenosine delivery, fostering human mesenchymal stromal cell (hMSC) differentiation into functional bone cells. The study investigates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive media. Insights into adenosine-modulated signalling pathways during MSC differentiation, with osteogenic factors, provide a comprehensive understanding of the pathways involved. Analysing gene expression and metabolic profiles unravels adenosine's regulatory mechanisms in MSC differentiation. Sustained adenosine release from microparticles induces mineralization, synergizing with osteogenic media supplements, showcasing the potential of adenosine for treating critical bone defects and metabolic disorders. This study highlights the efficacy of a polymeric microparticle-based delivery system, offering novel strategies for bone repair. Unveiling adenosine's roles and associated signalling pathways advances our comprehension of molecular mechanisms steering bone regeneration, propelling innovative biomaterial, combined with metabolites, approaches for clinical use.

Sustained-release nitrogen fertilizer delivery systems based on carboxymethyl cellulose-grafted polyacrylamide: Swelling and release kinetics

Sustained or controlled-release delivery systems can enhance functions such as nutrient usage; minimize soil contamination, and reduce the required fertilizer dose. This paper reports the development of a carboxymethyl cellulose-g-polyacrylamide copolymer (CMC-g-PAM) as a sustained and slow-release fertilizer carrier for urea. The developed copolymer was characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), and thermo gravimetric analysis (TG). The grafting process increased the activation energy of CMC from 0.1521 to 0.5952 J/mol with a higher loading percentage of 72.140.85% using a 15% urea solution. The swelling ratio is significantly dependent on the pH. The maximum swelling ratio of 1199.58% at pH 9. However, Swelling follows a pseudo-first-order reaction with the maximum swelling ratio in a saline of 349.76%.The CMC-g-PAM copolymer loaded with urea exhibited sustained and slow release, with the maximum cumulative percentage of 69.12% at pH 9 and 38.94% in saline. Urea release from the CMC-g-PAM copolymer followed the first-order, Fickian, and biexponential biphasic release mechanisms. The release of the CMC-g-PAM copolymer loaded with urea is a complicated process governed by diffusion and a biphasic releasing profile.

Olive oil loaded alginate milliparticle with chitosan coating: fabrication and evaluation

PurposeParticles are of the controlled release delivery systems. Also, topically applied olive oil has a protective effect against ultraviolet B (UVB) exposure. Due to its sensitivity to oxidation, various studies have investigated the production of olive oil particles. The purpose of this study was to use chitosan and sodium alginate as the vehicle polymers for olive oil.Design/methodology/approachThe gelation method used to prepare the sodium alginate miliparticles containing olive oil and particles were coated with chitosan. Morphology and size, zeta potential, infrared spectrum of olive oil miliparticles, encapsulation efficiency and oil release profile were investigated. Among 12 primary fabricated formulations, formulations F5 (olive oil loaded alginate miliparticles) and F11 (olive oil loaded alginate miliparticles + chitosan coat) were selected for further evaluations.FindingsThe size of the miliparticles was in the range of 1,100–1,600 µm. Particles had a spherical appearance, and chitosan coat made a smoother surface according to the scanning electron microscopy. The zeta potential of miliparticles were −30 mV for F5 and +2.7 mV for F11. Fourier transform infrared analysis showed that there was no interaction between olive oil and other excipients. Encapsulation efficiency showed the highest value of 85% in 1:4 (olive oil:alginate solution) miliparticles in F11. Release study indicated a maximum release of 68.22% for F5 and 60.68% for F11 in 24 h (p-value < 0.016). Therefore, coating with chitosan had a marked effect on slowing the release of olive oil. These results indicated that olive oil in various amounts can be successfully encapsulated into the sodium-alginate capsules cross-linked with glutaraldehyde.Originality/valueTo the best of the authors’ knowledge, no study has used chitosan and sodium alginate as the vehicle polymers for microencapsulation of olive oil.

In-situ forming biodegradable implants for sustained Fluocinolone acetonide release to the posterior eye: In-vitro and in-vivo investigations in rabbits

Delivering medication to the posterior segment of the eye presents a significant challenge. Intravitreal injection has emerged as the preferred method for drug delivery to this area. However, current injectable non-biodegradable implants for fluocinolone acetonide (FA) require surgical removal after prolonged drug release, potentially affecting patient compliance. This study aimed to develop an in-situ forming biodegradable implant (ISFBI) optimal formulation containing PLGA504H and PLGA756S (50:50 w/w%) with the additive NMP solvent. The goal was to achieve slow and controlled release of FA over a two-month period with lower burst release, following a single intravitreal injection. Through morphology, rheology, stability and in-vitro release evaluations, the optimal formulation demonstrated low viscosity (0.12–1.25 Pa. s) and sustained release of FA at a rate of 0.36 µg/day from the third day up to two months. Furthermore, histopathology and in-vivo studies were conducted after intravitreal injection of the optimal formulation in rabbits’ eye. Pharmacokinetic analysis demonstrated mean residence time (MRT) of 20.02 ± 0.6 days, half-life (t1/2) of 18.80 ± 0.4 days, and clearance (Cl) of 0.29 ± 0.03 ml/h for FA in the vitreous humor, indicating sustained and slow absorption of FA by the targeted retinal tissue from vitrea over the two-month period and eliminating through the anterior section of the eye, as revealed by its presence in the aqueous humor. Additionally, FA exhibited no detection in the blood and no evidence of systemic side effects or damage on the retinal layer and other organs. Based on these findings, it can be concluded that in-situ forming injectable biodegradable PLGA implants can show promise as a long-acting and controlled-release system for intraocular drug delivery.

Preparation and Characterization of Theophylline Controlled Release Matrix System Incorporating Poloxamer 407, Stearyl Alcohol, and Hydroxypropyl Methylcellulose: A Novel Formulation and Development Study.

Theophylline (THN), a bronchodilator with potential applications in emerging conditions like COVID-19, requires a controlled-release delivery system due to its narrow therapeutic range and short half-life. This need is particularly crucial as some existing formulations demonstrate impaired functionality. This study aims to develop a new 12-h controlled-release matrix system (CRMS) in the form of a capsule to optimize dosing intervals. CRMSs were developed using varying proportions of poloxamer 407 (P-407), stearyl alcohol (STA), and hydroxypropyl methylcellulose (HPMC) through the fusion technique. Their in vitro dissolution profiles were then compared with an FDA-approved THN drug across different pH media. The candidate formulation underwent characterization using X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Additionally, a comprehensive stability study was conducted. In vitro studies showed that adjusting the concentrations of excipients effectively controlled drug release. Notably, the CRMS formulation 15 (CRMS-F15), which was composed of 30% P-407, 30% STA, and 10% HPMC, closely matched the 12 h controlled-release profile of an FDA-approved drug across various pH media. Characterization techniques verified the successful dispersion of the drug within the matrix. Furthermore, CRMS-F15 maintained a consistent controlled drug release and demonstrated stability under a range of storage conditions. The newly developed CRMS-F15 achieved a 12 h controlled release, comparable to its FDA-approved counterpart.

Effect of Hydration Forms and Polymer Grades on Theophylline Controlled-Release Tablet: An Assessment and Evaluation.

Drug release from controlled release delivery systems is influenced by various factors, including the polymer's grade and the drug's hydration form. This study aimed to investigate the impact of these factors on the controlled release of theophylline (THN). This research compares the monohydrate form found in branded products with the anhydrous form in generic equivalents, each formulated with different polymer grades. Quality control assessment was conducted alongside in vitro evaluation, complemented by various analytical techniques such as X-ray diffraction (XRD) and scanning electron microscopy (SEM). Additionally, thermal analyses using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed. Quality control assessments demonstrated that the generic tablets exhibited lower average weight and resistance force compared to the branded ones. In vitro tests revealed that generic tablets released contents within 120 min, compared to 720 min for the branded counterpart. Characterization using XRD and SEM identified disparities in crystallinity and particle distribution between the three samples. Additionally, the thermal analysis indicated consistent endothermic peaks across all samples, albeit with minor variations in heat flow and decomposition temperatures between the two products. This study demonstrated that variations in polymer grade and hydration form significantly impact THN release.

Engineered therapeutic proteins for sustained-release drug delivery systems.

Proteins play a vital role in diverse biological processes in the human body, and protein therapeutics have been applied to treat different diseases such as cancers, genetic disorders, autoimmunity, and inflammation. Protein therapeutics have demonstrated their advantages, such as specific pharmaceutical effects, low toxicity, and strong solubility. However, several disadvantages arise in clinical applications, including short half-life, immunogenicity, and low permeation, leading to reduced drug effectiveness. The structure of protein therapeutics can be modified to increase molecular size, leading to prolonged stability and increased plasma half-life. Notably, the controlled-release delivery systems for the sustained release of protein drugs and preserving the stability of cargo proteins are envisioned as a potential approach to overcome these challenges. In this review, we summarize recent research progress related to structural modifications (PEGylation, glycosylation, poly amino acid modification, and molecular biology-based strategies) and promising long-term delivery systems, such as polymer-based systems (injectable gel/implants, microparticles, nanoparticles, micro/nanogels, functional polymers), lipid-based systems (liposomes, solid lipid nanoparticles, nanostructured lipid carriers), and inorganic nanoparticles exploited for protein therapeutics. STATEMENT OF SIGNIFICANCE: In this review, we highlight recent advances concerning modifying proteins directly to enhance their stability and functionality and discuss state-of-the-art methods for the delivery and controlled long-term release of active protein therapeutics to their target site. In terms of drug modifications, four widely used strategies, including PEGylation, poly amino acid modification, glycosylation, and genetic, are discussed. As for drug delivery systems, we emphasize recent progress relating to polymer-based systems, lipid-based systems developed, and inorganic nanoparticles for protein sustained-release delivery. This review points out the areas requiring focused research attention before the full potential of protein therapeutics for human health and disease can be realized.

Prolonged Anesthesia Effects of Locally Administered Ropivacaine via Electrospun Poly(caprolactone) Fibrous Membranes.

Prolonged analgesia is important to safeguard the patient's comfort and safety during and after surgery in clinical practice. To meet the demand for prolonged analgesia, medical professionals often resort to increasing drug frequency, which may lead to poor patient compliance and serious complications due to drug overdose. Therefore, it is of great interest to develop controlled-release drug delivery systems for local anesthetics, enabling slow and controlled drug release to prolong the analgesic effect and minimize systemic toxicity. In this study, we utilized an electrospinning technique to fabricate nonwoven poly(caprolactone) (PCL) fibrous membranes loaded with Ropivacaine and performed proof-of-principle experiments on both in vitro drug release tests and in vivo animal tests, to further prolong the analgesic effect of Ropivacaine and improve postoperative local pain management and chronic pain treatment. Material characterization and in vitro drug release studies confirmed the feasibility of the Ropivacaine-loaded PCL fibrous membranes for sustained release. The drug loading content and drug loading efficiency of Ropivacaine-loaded fibrous membrane are 8.7 ± 0.3 wt% and 96 ± 3 wt%, respectively. Evaluation in an animal model demonstrated prolonged anesthesia effects along with excellent biocompatibility and stability. At 72 h, the cumulative release accounted for approximately 50% of the drug loading content. This study offers novel approaches and strategies for clinical postoperative pain management and chronic pain treatment, while providing new insights and directions for the design of local anesthetic controlled-release delivery systems.

Angelica archangelica essential oil loaded chitosan nanoemulsion as edible coating for preservation of table grape fruit against Botrytis cinerea contamination and storage quality deterioration

The present study deals with the encapsulation of Angelica archangelica essential oil into chitosan nanoemulsion (AAEO-NE) and evaluation of its effectiveness as novel coating agent with innovative controlled release delivery system for protection of table grape (Vitis vinifera L.) fruit against Botrytis cinerea contamination, and quality deterioration over 30 d of storage (25 ± 2 °C, Relative humidity 85%). The AAEO-NE was characterized through dynamic light scattering (DLS), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The mean particle size was tended to increase from 53.69 to 98.63 nm, while ζ-potential was decreased from + 32.3 to + 23.5 mV. Fourier transform infrared spectroscopy (FTIR), and X-ray diffractometry (XRD) analyses suggested intermolecular interaction followed by effective encompassment of AAEO into chitosan nanomatrix. In vitro release study confirmed the biphasic and controlled delivery of AAEO, essentially required for its long term effectiveness in view of maintaining postharvest quality of the treated fruit. The antifungal efficacy of unencapsulated AAEO against B. cinerea was found as 5.5 g L−1, and noticed to be enhanced (2.5 g L−1) after encapsulation into chitosan nanoemulsion. The inhibition of ergosterol biosynthesis followed by subsequent enhancement of ions leakage after treatment of B. cinerea cells with AAEO-NE suggested plasma membrane as major site of antifungal activity. During in vivo investigation, AAEO-NE coating inhibited the contamination of B. cinerea and maintained the quality attributes like weight, titrable acidity, total soluble solids, phenolic content, and pH of table grape fruit. Additionally, the preservation of enzymatic antioxidants, reduced respiration rate, and better sensory qualities of coated table grape fruit recommend the functional potentiality of chitosan as biocompatible wall matrix to encapsulate AAEO and application as novel nano-green smart coating based fungitoxicant and shelf-life enhancer in fruit and agricultural industries.

Preparation and Administration of a Controlled-Release Delivery System of Chitosan Hydrogel loaded with Methadone and Piroxicam in Experimental Defect of Tibial in Rats; Histopathological Evaluation

Purpose: In this study, a controlled-release drug delivery system loaded with piroxicam and methadone was synthesized and used subcutaneously in rats with experimental tibial defect, and healing were assessed histopathologically.&#x0D; Materials and Methods: For this purpose, 100 adult female rats were randomly divided into five equal groups; control group, chitosan group, piroxicam group, methadone group, and piroxicam-methadone group. The morphological structure of the synthesized drug systems was studied by scanning electron microscope. In addition, the structure of the hydrogels was investigated by Fourier transform infrared spectroscopy and while releasing the hydrogels' gelation time, the release of piroxicam and methadone from the hydrogels was evaluated in vitro.&#x0D; Results: Histological results of the 3rd day of the study showed the lowest extent and severity of inflammation in the chitosan, piroxicam, and piroxicam-methadone groups, while on the 7th day, tissue inflammation and the extent of bleeding were lower in the piroxicam, methadone, and piroxicam-methadone groups than in the other groups. Evaluation of new bone formation on day 21 showed that the chitosan, piroxicam, and methadone groups had better repair than the other groups.&#x0D; Conclusion: It seems that in the control group that did not receive any treatment intervention, following the experimental bone defect, the highest inflammatory response was observed in histological examination and finally the weakest bone repair. On the other hand, the presence of piroxicam, methadone, and chitosan in the piroxicam-methadone group (all of which have anti-inflammatory effects) also seems to have a negative effect on the repair.

Preparation of multivesicular liposomes for the loco-regional delivery of Vancomycin hydrochloride using active loading method: drug release and antimicrobial properties

Over the last few years, among controlled-release delivery systems, multivesicular liposomes (MVLs) have attracted attention due to their unique benefits as a loco-regional drug delivery system. Considering the clinical limitations of the current treatment strategies for osteomyelitis, MVLs can be a suitable carrier for the local delivery of effective antibiotics. This study aimed to prepare vancomycin hydrochloride (VAN HL) loaded MVLs using the active loading method which to the best of our knowledge has not been previously reported. Empty MVLS were prepared by the double emulsion (w/o/w) method and VAN HL was loaded into the prepared liposomes by the ammonium gradient method. After full characterization, the release profile of VAN HL from MVLs was assessed at two different pH values (5.5 and 7.4), and compared with the release profile of the free drug and also passively loaded MVLs. In vitro antimicrobial activities were evaluated using the disc diffusion method. Our results demonstrated that the encapsulation efficiency was higher than 90% in the optimum actively loaded MVL. The free VAN HL was released within 6-8 h, while the passively loaded MVLs and the optimum actively loaded MVL formulation released the drug in 6 days and up to 19 days, respectively. The released drug showed effective antibacterial activity against osteomyelitis-causing pathogens. In conclusion, the prepared formulation offered the advantages of sustained-release properties, appropriate particle size as well as being composed of biocompatible materials, and thus could be a promising candidate for the loco-regional delivery of VAN HL and the management of osteomyelitis.

Green Nanopesticide: pH-Responsive Eco-Friendly Pillar[5]arene-Modified Selenium Nanoparticles for Smart Delivery of Carbendazim to Suppress Sclerotinia Diseases

Controlled-release delivery systems have been widely used to improve the efficacy and bioavailability of pesticides and minimize environmental risks. Herein, a fungicide carbendazim (CBZ)-loaded, a kind of nanovalve including trimethylammoniumpillar[5]arene (AP5), and methyl orange (MO)-functionalized mesoporous selenium (MSe) nanopesticides (CBZ@AP5/MSe⊃MO) were prepared. The nanovalve endowed CBZ@AP5/MSe⊃MO with a pH-responsive property, so the CBZ@AP5/MSe⊃MO can respond to the microenvironment of the pathogen Sclerotinia sclerotiorum (S. sclerotiorum). First, MO was shed due to protonation, and AP5-functionalized MSe gradually dissolved in an acid environment. Finally, CBZ was released rapidly. It is reported that AP5 and MO as the host and guest functionalized mesoporous selenium (MSe) have never been applied to agriculture. In vitro release experiments showed that the cumulative release rate of CBZ at pH 4.5 was 1.74 times higher than that in a neutral environment. In addition, we found that the contact angle of the CBZ@AP5/MSe⊃MO in maize and rape leaves was effectively decreased, which could retain more in the leaves after washout. It can also decrease the dry biomass and the reducing sugar of S.sclerotiorum. The CBZ@AP5/MSe⊃MO holds a good safety profile for plants, animal cells, and the environment owing to the targeted release properties. These results suggest that CBZ@AP5/MSe⊃MO is an environmentally friendly and effective drug-loaded system against S. sclerotiorum. It provides a new strategy for the design and development of nanopesticides and the control of S. sclerotiorum.

A MOF-based pH-responsive dual controlled-release system for herbicide pretilachlor and safener AD-67 delivery that enhances the herbicidal efficacy and reduces side effects

The herbicide-safener dual controlled release system AD-67@Pre@ZIF-67 was successfully prepared for the high efficiency and low toxicity of herbicide.

Development of Growth Factor Releasing Hyaluronic Acid-Based Hydrogel for Pulp Regeneration: A Preliminary Study.

Growth factors play essential roles as signaling molecules in pulp regeneration. We investigated the effect of a hyaluronic acid (HA)-collagen hybrid hydrogel with controlled release of fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-BB on human pulp regeneration. The cell interaction and cytotoxicity of the HA-collagen hybrid hydrogel, the release kinetics of each growth factor, and the effects of the released growth factors on pulp cell proliferation were examined. The vitality of pulp cells was maintained. The amounts of FGF-2 and PDGF-BB released over 7 days were 68% and 50%, respectively. Groups with a different concentration of growth factor (FGF-2: 100, 200, 500, and 1000 ng/mL; PDGF-BB: 10, 50, 100, 200, and 500 ng/mL) were experimented on days 1, 3, 5, and 7. Considering FGF-2 concentration, significantly increased pulp cell proliferation was observed on days 1, 3, 5, and 7 in the 100 ng/mL group and on days 3, 5, and 7 in the 200 ng/mL group. In the case of PDGF-BB concentration, significantly increased pulp cell proliferation was observed at all four time points in the 100 ng/mL group and on days 3, 5, and 7 in the 50, 200, and 500 ng/mL groups. This indicates that the optimal concentration of FGF-2 and PDGF-BB for pulp cell proliferation was 100 ng/mL and that the HA-collagen hybrid hydrogel has potential as a controlled release delivery system for FGF-2 and PDGF-BB.

Producing mixed-soy protein adsorption layers on alginate microgels to controlled-release β-carotene

In this study, the effects of soy protein isolate (SPI) on the morphology, encapsulation efficiency, storage stability, swelling behavior, and in vitro digestion behavior of calcium alginate (CA) microgels were investigated. CA and calcium alginate-SPI (CAS) microgels with encapsulated β-carotene were prepared by extruding a mixture of alginate and SPI using a co-extrusion technique, followed by cross-linking with Ca2+. All microgels exhibited homogeneous sizes and spherical shapes, and CAS microgels showed high levels of protein loading efficiency. The encapsulation efficiency and storage stability of β-carotene within CAS microgels were higher than those within CA microgels. The introduction of SPI into CAS microgels resulted in a higher degree of gel size shrinkage in gastric fluid and a lower degree of swelling in intestinal fluid compared to CA microgels. In vitro digestion was conducted to investigate the effects of the addition of SPI on the release behavior of CA and CAS microgels. Results obtained showed that CAS microgels were more resistant to simulated gastric fluid than CA microgels. Cryo-scanning electron microscopy (cryo-SEM) and confocal laser scanning microscopy (CLSM) observations indicated that the release behavior was dependent on the porosity of the CA and CAS microgels, and the porosity was influenced by the concentration of SPI. This study showed that the introduction of SPI to CA microgels can lead to the development of an effective controlled release delivery system.

Fabrication of a controlled-release delivery system for relieving sciatica nerve pain using an ultrasound-responsive microcapsule.

Lidocaine, a potent local anesthetic, is clinically used in nerve block and pain management. However, due to its short half-life, repeated administration is required. For this reason, here we designed and prepared a lidocaine-encapsulated polylactic acid-glycolic acid (Lidocaine@PLGA) microcapsule with ultrasound responsiveness to relieve the sciatica nerve pain. With a premixed membrane emulsification strategy, the fabricated lidocaine-embedded microcapsules possessed uniform particle size, good stability, injectability, and long-term sustained release both in vitro and in vivo. More importantly, Lidocaine@PLGA microcapsules had the function of ultrasonic responsive release, which made the drug release controllable with the effect of on-off administration. Our research showed that using ultrasound as a trigger switch could promote the rapid release of lidocaine from the microcapsules, achieving the dual effects of long-term sustained release and short-term ultrasound-triggered rapid release, which can enable the application of ultrasound-responsive Lidocaine@PLGA microcapsules to nerve root block and postoperative pain relief.

Thermo-sensitive composite microspheres incorporating cellulose nanocrystals for regulated drug release kinetics

Thermo-sensitive composite microspheres (TPCP) were developed to achieve the on-demand release of drugs. The TPCP microspheres were synthesized using Oil-in-Water (O/W) emulsion evaporation technique and then impregnated with thermo-sensitive polyethylene glycol (PEG). The addition of cellulose nanocrystals (CNCs) significantly enhance thermal stability, crystallization ability, and surface hydrophilicity of TPCP microspheres due to heterogeneous nucleation effect and hydrogen bonding interaction, resulting in stable microsphere structure. The thermal degradation temperature (Tmax) increased by 13.8 °C, and the crystallinity improved by 20.9 % for 10 % TPCP. The thermo-sensitive composite microspheres showed the regulated cumulative release according to in vitro human physiological temperature changes. Besides, four release kinetics and possible release mechanism of TPCP microspheres were provided. Such thermo-responsive composite microspheres with control microsphere sizes and high encapsulation rate may have the potential to the development of on-demand and advanced controlled-release delivery systems.