Recently, Poly (lactic-co-glycolic) Acid (PLGA) has garnered great attention as foundational material for biomedical applications due to inherent biocompatibility, and controlled rate of biodegradation facilitating the modification of surface properties and improved interaction with biological substrates. PLGA has been applied in drug conveyance, tissue engineering, controlled release of proteins, molecule-drugs, and other macromolecular entities. Varying nanoarchitectures utilizable for cancer imaging and therapy have been developed using PLGA and their clinical applications have been assessed. PLGA or nanoparticles (NPs) of PLGA has also been functionalized for tumor-targeting, diagnostic behavior and in vivo imaging. Therefore, this paper critically elucidates emerging trends in PLGA bone tissue engineering, PLGA-NPs tumor-targeting for cancer, imaging and therapy, as well as varying techniques for fabricating devices and parameters influencing their drug releasing rate and degradation. 

Emerging trends in Poly(lactic-co-glycolic) acid bionanoarchitectures and applications

The authors present a steady-state-, particle-size-, and dose-dependent dissolution-permeation model that describes particle dissolution within the concentration boundary layer (CBL) adjacent to a semipermeable surface. It is critical to understand how particle size and dose affect the behavior of dissolving particles in the presence of a CBL adjacent to a semipermeable surface both in vivo and in vitro. Control of particle size is ubiquitous in the pharmaceutical industry; however, traditional pharmaceutical assumptions of particle dissolution typically ignore particle dissolution within the length scale of the CBL. The CBL does not physically prevent particles from traveling to the semipermeable surface (mucus, epithelial barrier, synthetic membrane, etc.), and particle dissolution can occur within the CBL thickness (δC) if the particle is sufficiently small (∼dparticle ≤ δC). The total flux (the time rate transport of molecules across the membrane surface per unit area) was chosen as a surrogate parameter for measuring the additional mass generated by particles dissolving within the donor CBL. Mass transfer experiments aimed to measure the total flux of drug using an ultrathin large-area membrane diffusion cell described by Sinko et al. with a silicone-based membrane ( Mol. Pharmaceutics 2020, 17, (7) 2319-2328, DOI: 10.1021/acs.molpharmaceut.0c00040). Suspensions of ibuprofen, a model weak-acid drug, with three different particle-size distributions with average particle diameters of 6.6, 37.4, and 240 μm at multiple doses corresponding to a range of suspension concentrations with dimensionless dose numbers of 2.94, 14.7, 147, and 588 were used to test the model. Experimentally measured total flux across the semipermeable membrane/CBL region agreed with the predictions from the proposed model, and at a range of relatively low suspension concentrations, dependent on the average particle size, there was a measurable effect on the flux due to the difference in δC that formed at the membrane surface. Additionally, the dose-dependent total flux across the membrane was up to 10% higher than the flux predicted by the standard Higuchi-Hiestand dissolution model where the effects of confinement were ignored as described by Wang et al. ( Mol. Pharmaceutics 2012, 9 (5), 1052-1066, DOI: 10.1021/mp2002818).

Particle Size, Dose, and Confinement Affect Passive Diffusion Flux through the Membrane Concentration Boundary Layer.

Developing artificial material systems to rationally interfere with organelles is emerging as a promising route to regulate the behaviors and fate of cells, thus providing new therapeutic strategies. Herein, a DNA nanoparticles (DNPs)‐based material system is reported, which achieves controlled sequential assembly inside cells, and realizes specific interference toward mitochondria. Two types of DNPs are synthesized via radical polymerization, followed with cascade hybridization chain reaction of hairpin DNA with Cyanine5 (Cy5) for mitochondrial targeting, and with complementary sequences for base pairing, respectively. DNPs with Cy5 (Cy5‐DNPs) first entered cells to target mitochondria, and the other DNPs with complementary sequences entered cells after an interval to sequentially assemble with Cy5‐DNPs into aggregates via base pairing. Mitochondrial interference is achieved, including increased reactive oxygen species, decreased membrane potential, abnormal elevation of Ca2+ level, decreased adenosine triphosphate, and attenuated cellular migration rate. In particular, by regulating the intervals of two types of DNPs entering cells, the mitochondrial interference degree is controllably modulated. This work achieves regulated organelles interference via the precise controlled self‐assembly of DNA nanostructures inside cells, which is envisioned to have great potential in precision biomedicine.

Controlled Sequential Assembly of DNA Nanoparticles Inside Cells Enabling Mitochondrial Interference

Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that has limited treatment options. Current standard therapies, including surgery followed by radiotherapy and chemotherapy, are not very effective due to the rapid progression and recurrence of the tumor. Therefore, there is an urgent need for more effective treatments, such as combination therapy and localized drug delivery systems that can reduce systemic side effects. Recently, a handheld printer was developed that can deliver drugs directly to the tumor site. In this study, the feasibility of using this technology for localized co-delivery of temozolomide (TMZ) and deferiprone (DFP) to treat glioblastoma is showcased. A flexible drug-loaded mesh (GlioMesh) loaded with poly (lactic-co-glycolic acid) (PLGA) microparticles is printed, which shows the sustained release of both drugs for up to a month. The effectiveness of the printed drug-eluting mesh in terms of tumor toxicity and invasion inhibition is evaluated using a 3D micro-physiological system on a plate and the formation of GBM tumoroids within the microenvironment. The proposed in vitro model can identify the effective combination doses of TMZ and DFP in a sustained drug delivery platform. Additionally, our approach shows promise in GB therapy by enabling localized delivery of multiple drugs, preventing off-target cytotoxic effects.

In Vitro Glioblastoma Model on a Plate for Localized Drug Release Study from a 3D-Printed Drug-Eluted Hydrogel Mesh

The present investigation offers a thorough bibliometric exploration spotlighting the pivotal utilization of zinc oxide nanostructures, encompassing both zero‐dimensional (0D) nanoparticles and one‐dimensional (1D) nanostructures, within the realm of nanotechnology‐driven drug delivery systems. This analysis particularly illuminates the distinctive potential of these nanostructures in the cancer therapy context, not merely as carriers and deliverers of pharmaceutical agents, but as entities capable of selectively inducing apoptosis in cancer cells through the orchestrated generation of reactive oxygen species (ROS). Recent research endeavors notably underscore the application prospects of ZnO nanostructures in domains like DNA cleavage, bioimaging, and agricultural defense mechanisms. Moreover, the study elucidates the pronounced enhancement in solubility and biocompatibility that these nanostructures bring about when harmoniously integrated into polymeric nanocomposites. Concomitantly, the involvement of polymers in this symbiotic system is unveiled, wherein they play a multifaceted role in dictating release selectivity, thereby facilitating targeted and efficacious interactions with tissues. Functionally engineered polymeric nanocomposites emerge as promising candidates for targeted delivery modalities in cancer treatment, demonstrating an affinity for specific cell receptors and exhibiting enhanced cellular uptake within the size range of 100–200 nm. The study unearths robust associations among pivotal research terminologies through an exhaustive analysis of Link Strength Between Items (LSBI), culminating in the presentation of a cogent map delineating the evolving trends and forthcoming trajectories in this dynamic domain. In summation, this all‐encompassing bibliometric inquiry serves as a poignant testament to the prodigious potential of zinc oxide nanostructures in the realm of forthcoming nanotechnology‐driven drug delivery paradigms.

A Data Mining Study of Zinc Oxide Nanostructures Utilization in Drug Delivery Nanosystems

Size-dependent cellular uptake and sustained drug release of PLGA particles

Subcellular localization of DNA nanodevices and their applications.

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Size-dependent cellular uptake and sustained drug release of PLGA particles

Subcellular localization of DNA nanodevices and their applications.