Drug delivery strategies for local immunomodulation hold tremendous promise compared to current clinical gold-standard systemic immunosuppression as they could improve the benefit to risk ratio of life-saving or life-enhancing transplants. Such strategies have facilitated prolonged graft survival in animal models at lower drug doses while minimizing off-target effects. Despite the promising outcomes in preclinical animal studies, progression of these strategies to clinical trials has faced challenges. A comprehensive understanding of the translational barriers is a critical first step towards clinical validation of effective immunomodulatory drug delivery protocols proven for safety and tolerability in pre-clinical animal models. This review overviews the current state-of-the-art in local immunomodulatory strategies for transplantation and outlines the key challenges hindering their clinical translation.

Hydrogel-based depots typically tend to remain where injected and have excellent biocompatibility but are relatively poor at controlling drug release. Nanoparticles (NPs) typically have the opposite properties. The smaller the NPs are, the more likely they are to leave the site of injection. Their biocompatibility is variable depending on the material but can be poor. However, NPs can be good at controlling drug release. In these and other properties, combining NPs and hydrogels can leverage their advantages and negate their disadvantages. This review highlights the rationale for hybrid NP-hydrogel systems in drug delivery, the basic methods of producing them, and examples where combining the two systems addressed specific problems.

In recent years, development of biopolymeric nanofibers as an active biodegradable packaging system has attracted specific attention. The objective of this research was to develop zein-based electrospun nanofibers (NFs) incorporated with geraniol-loaded nanoliposomes (G-loaded NLPs). Geraniol was encapsulated into NLPs with an efficiency of 79.23%. The particle size and zeta potential of G-loaded NLPs were 121.50 nm and -38.30 mV, respectively. The successful loading of geraniol in the NLPs was approved by Fourier transform infrared (FT-IR) spectroscopy. The liposomal vesicles showed spherical shapes. G-loaded NLPs were added in the zein-based electrospun NFs at three different concentrations (0.25, 0.5, and 1%w/v). All NFs samples exhibited fibrillar structure. The increase of NLPs concentration enhanced the thermal stability of the NFs. However, the crystalline structure of zein NFs did not change by the addition of G-loaded NLPs. The highest surface hydrophobicity was related to the NFs containing 1% G-loaded NLPs. The mechanical parameters of NFs depend on the concentration of NLPs. The NFs incorporated with G-loaded NLPs showed inhibition activity against four foodborne pathogenic bacteria (Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella typhimurium) with an inhibition zone of 4.5-22 mm. Moreover, the α-diphenyl-β-picrylhydrazyl (DPPH) scavenging activity of NFs samples was located at the range of 20%-48%. These findings represent the Efficiency of the G-loaded NLPs for use as bioactive compound in the zein-based NFs as an active packaging material.

The convergence of polymer and pharmaceutical sciences has advanced drug delivery systems significantly. Carbohydrate polymers, especially carboxymethylated ones, offer versatile benefits for pharmaceuticals. Interpenetrating polymer networks (IPNs) combine synthetic and natural polymers to enhance drug delivery. The study aims to develop IPN beads using sodium carboxymethyl cellulose (SCMC) and carboxymethyl konjac glucomannan (CMKGM) for controlled release of ibuprofen (IB) after oral administration. Objectives include formulation optimization, characterization of physicochemical properties, evaluation of pH-dependent swelling and drug release behaviors to advance biocompatible and efficient oral drug delivery systems. The beads were analyzed using SEM, FTIR, DSC, and XRD techniques. Different ratio of polymers (CMKGM:SCMS) and crosslinker concentrations (2&4 %w/v) were used, significantly impacting bead size, swelling, drug encapsulation, and release characteristics. DSC results indicated higher thermal stability in IPN beads compared to native polymers. XRD revealed IB dispersion within the polymer matrix. IPN beads size ranged from 580 ± 0.56 to 324 ± 0.27 μm, with a nearly spherical shape. IPN beads exhibited continuous release in alkaline conditions (pH 7.4) and minimal release in acidic media (pH 1.2). These findings suggest that the formulated IPN beads can modulate drug release in both acidic and alkaline environments, potentially mitigating the gastric adverse effects often associated with oral administration of IB.

New nano/microcarriers of pesticides represent a highly promising novel field for sustainable pest management. However, despite extensive laboratory research, few studies on the design and evaluation of nanopesticides for field applications exist. In this study, we present a straightforward and green synthetic method of ultrasonic-assisted and hydrogen-bonded self-assembly at the oil-water interface for the synthesis of polylactic acid (PLA) microspheres encapsulating chlorantraniliprole (CAP), with precise control over the size of the microspheres. The resulting CAP-loaded PLA microspheres (CAP-PLA MS) exhibit both high pesticide encapsulation efficiency and stability in natural environments. It has been determined that non-Fickian diffusion mainly controls pesticide release, thus enabling dynamic control over molecular transport speeds. Importantly, our functional CAP-PLA MS demonstrates superior sustained pesticide release performance under both laboratory and field conditions while maintaining better exceptional insecticidal efficacy than normal CAP in controlling O. nubilalis at a concentration of 30 or 45 g/ha. Consequently, we propose that our functional PLA microspheres could serve as ideal pesticide carriers in the sustained treatment of O. nubilalis.

Cartilage is severely limited in self-repair after damage, and tissue engineering scaffold transplantation is considered the most promising strategy for cartilage regeneration. However, scaffolds without cells and growth factors, which can effectively avoid long cell culture times, high risk of infection, and susceptibility to contamination, remain scarce. Hence, we developed a cell- and growth factor-dual free hierarchically structured nanofibrous sponge to mimic the extracellular matrix, in which the encapsulated core-shell nanofibers served both as mechanical supports and as long-lasting carriers for bioactive biomass molecules (glucosamine sulfate). Under the protection of the nanofibers in this designed sponge, glucosamine sulfate could be released continuously for at least 30 days, which significantly accelerated the repair of cartilage tissue in a rat cartilage defect model. Moreover, the nanofibrous sponge based on carboxymethyl chitosan as the framework could effectively fill irregular cartilage defects, adapt to the dynamic changes during cartilage movement, and maintain almost 100 % elasticity even after multiple compression cycles. This strategy, which combines fiber freeze-shaping technology with a controlled-release method for encapsulating bioactivity, allows for the assembly of porous bionic scaffolds with hierarchical nanofiber structure, providing a novel and safe approach to tissue repair.

The instability of anthocyanins significantly reduces their bioavailability as food nutrients. This proof-of-concept study aimed to develop efficient carriers for anthocyanins to overcome this challenge. Characterization of the hydrogels via SEM (scanning electron microscope) and rheological analysis revealed the formation of typical gel structures. MTT (methyl thiazolyl tetrazolium) and hemolysis assays confirmed that their high biocompatibility. Encapsulation efficiency analysis and fluorescence microscopy images demonstrated successful and efficient encapsulation of anthocyanins by pH-responsive hydrogels. Stability studies further validated the effect of peptide hydrogels in helping anthocyanin molecules withstand factors such as gastric acid, high temperatures, and heavy metals. Subsequently, responsive studies in simulated gastric (intestinal) fluid demonstrated that the pH-responsive peptide hydrogels could protect anthocyanin molecules from gastric acid while achieving rapid and complete release in intestinal fluid environments. These results indicate that these peptide hydrogels could stabilize anthocyanins and facilitate their controlled release, potentially leading to personalized delivery systems.

OBJECTIVE: Acyclovir (ACY) is used to treat oral viral herpes but has low solubility and bioavailability. Stearic acid (SA) is lipophilic and can be combined with drugs. Therefore, this study aimed to characterize the properties of SA nanoparticles in increasing the cellular uptake of ACY by oral epithelial cells. The hypothesis was that SA nanoparticles increase sustained ACY release, are stable, and increase drug uptake.
METHODS: The production parameters (duration and amplitude of sonication) were optimized to produce solid lipid nanoparticles (SLN) of SA-containing ACY. Particle stability was characterized under different storage conditions (4 °C and 37 °C for 1, 15, and 45 days). SLN were further characterized for their pharmacokinetic profile, cytotoxicity, in vitro permeability, and ability to modulate gene expression and promote ACY uptake by oral epithelial cells.
RESULTS: Pharmacokinetic studies revealed sustained and diffusional release of ACY from the SLN, with an initial burst release of 15 min. After 45 d of storage, SLN kept at both 4 °C and 37 °C showed a maximum release of > 90 % of the drug at 120 min. Cells treated with SLN presented a significantly higher intracellular drug content than those treated with ACY and significantly increased the genetic expression of TJP-1, OCLN, and ECAD.
CONCLUSIONS: The hypothesis was accepted as SA nanoparticles containing ACY can sustain drug delivery and enhance its absorption into epithelial cells. Therefore, SA nanoparticles are promising for improving ACY uptake in treating oral herpes and other infections caused by HSV-1.

Aim: We synthesized MgO NPs via sol-gel reaction and investigated them as carriers to deliver Mg2+ to the affected joint for osteoarthritis (OA). Materials & methods: The physicochemical properties of samples were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS) and x-ray diffraction (XRD). The release of Mg2+ was monitored by ICP-MS. The potential cytotoxicity was evaluated using MTT assay. The efficacy and biosafety were evaluated in a rabbit OA model. Results: MgO NPs can prolong the Mg2+ release time from 0.5 h to 12 h. No significant cytotoxicity was observed when concentrations below 250 μg/ml. Intra-articular samples could effectively alleviate the degeneration and destruction of the cartilage. Conclusion: this study demonstrates the potential of MgO NPs as a safe and effective treatment of OA. Simultaneously, the size of the particles may play a significant role in influencing the therapeutic outcome.
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Controlled-release drug delivery systems (CRDDS) are more beneficial than conventional immediate release (IRDDS) for reduced intake, prolonged duration of action, lesser adverse effects, higher bioavailability, etc. The preparation of CRDDS is more complex than IRDDS. The hot melt extrusion (HME) technique is used for developing amorphous solid dispersion of poorly water soluble drugs to improve their dissolution rate and oral bioavailability. HME can be employed to develop CRDDS. Sustained release delivery systems (SRDDS), usually given orally, can also be developed using HME. This technique has the advantages of using no organic solvent, converting crystalline drugs to amorphous, improving bioavailability, etc. However, the heat sensitivity of drugs, miscibility between drug-polymer, and the availability of a few polymers are some of the challenges HME faces in developing CRDDS and SRDDS. The selection of a suitable polymer and the optimization of the process with the help of the QbD principle are two important aspects of the successful application of HME. In this review, strategies to prepare SRDDS and CRDDS using HME are discussed with its applications in research.