Drug Delivery Properties Research Articles

The effect of chemical composition and morphology on the drug delivery properties of hydroxyapatite-based biomaterials

In the case of orthopedic and dental interventions, local antibiotic therapy reduces significantly the risk associated with the intervention. The aim of this study was the preparation and characterization of pure hydroxyapatite (HA), Si- and Mg-doped HA, which ensures the sustained release of doxycycline, and the investigation of the parameters, which were crucial for the drug release. The carriers were synthesized using the precipitation method. In order to achieve different morphologies, traditional drying and spray drying methods were used: Si-doped HA was prepared using two different sources of Si, Na2SiO3 and Ludox AS-40, while (Mg(NO3)2)*6H2O was used for substitution with Mg. The carriers were characterized by XRD, SEM, EDX and TG/DTA methods, and the ion incorporation was also confirmed by lattice parameters calculations. Doxy was bound on the carriers by physical adsorption, the adsorption capacity increased proportionally by increasing the concentration of the initial Doxy solutions (10, 15, 20, 25 g/L). The investigated systems showed different releases with the change of the dissolution medium (in the case of HA microspheres, the release in PBS was twice as high as in SBF), chemical composition and morphology of the carriers. The retard effect of the carriers was improved by the spherical morphology, and the reduced release by ion substitution in both SBF and PBS increased as follows: HA < HASi1<HAMg < HASi2. The release mechanism of Doxy was discussed through five different release kinetics models.

Dual gatekeepers-modified mesoporous organic silica nanoparticles for synergistic photothermal-chemotherapy of breast cancer

HypothesisConstruction of dual gatekeepers-functionalized mesoporous organic silica nanoparticles (MONs) with both physical and chemical mechanisms for modulated drug delivery properties provides one solution to the extracellular stability vs. intracellular high therapeutic efficiency of MONs that hold great potential for clinical translations. ExperimentsWe reported herein facile construction of diselenium-bridged MONs decorated with dual gatekeepers, i.e., azobenzene (Azo)/polydopamine (PDA) for both physical and chemical modulated drug delivery properties. Specifically, Azo can act as a physical barrier to block DOX in the mesoporous structure of MONs for extracellular safe encapsulation. The PDA outer corona serves not only as a chemical barrier with acidic pH-modulated permeability for double insurance of minimized DOX leakage in the extracellular blood circulation but also for inducing a PTT effect for synergistic PTT and chemotherapy of breast cancer. FindingsAn optimized formulation, DOX@(MONs-Azo3)@PDA resulted in approximately 1.5 and 2.4 fold lower IC50 values than DOX@(MONs-Azo3) and (MONs-Azo3)@PDA controls in MCF-7 cells, respectively, and further mediated complete tumor eradication in 4T1 tumor-bearing BALB/c mice with insignificant systematic toxicity due to the synergistic PTT and chemotherapy with enhanced therapeutic efficiency.

Controlled Protein Activities with Viral Proteases, Antiviral Peptides, and Antiviral Drugs.

Chemical control of protein activity is a powerful tool for scientific study, synthetic biology, and cell therapy; however, for broad use, effective chemical inducer systems must minimally crosstalk with endogenous processes and exhibit desirable drug delivery properties. Accordingly, the drug-controllable proteolytic activity of hepatitis C cis-protease NS3 and its associated antiviral drugs have been used to regulate protein activity and gene modulation. These tools advantageously exploit non-eukaryotic and non-prokaryotic proteins and clinically approved inhibitors. Here, we expand the toolkit by utilizing catalytically inactive NS3 protease as a high affinity binder to genetically encoded, antiviral peptides. Through our approach, we create NS3-peptide complexes that can be displaced by FDA-approved drugs to modulate transcription, cell signaling, and split-protein complementation. With our developed system, we invented a new mechanism to allosterically regulate Cre recombinase. Allosteric Cre regulation with NS3 ligands enables orthogonal recombination tools in eukaryotic cells and functions in divergent organisms to control prokaryotic recombinase activity.

Hybrid Shear-thinning Hydrogel Integrating Hyaluronic Acid with ROS-Responsive Nanoparticles.

Nanoparticle (NP) supra-assembly offers unique opportunities to tune macroscopic hydrogels' mechanical strength, material degradation, and drug delivery properties. Here, synthetic, reactive oxygen species (ROS)-responsive NPs are physically crosslinked with hyaluronic acid (HA) through guest-host chemistry to create shear-thinning NP/HA hydrogels. A library of triblock copolymers composed of poly(propylene sulfide)-bl-poly(N,N-dimethylacrylamide)-bl-poly(N,N-dimethylacrylamide-co-N-(1-adamantyl)acrylamide) are synthesized with varied triblock architectures and adamantane grafting densities and then self-assembled into NPs displaying adamantane on their corona. Self-assembled NPs are mixed with β-cyclodextrin grafted HA to yield eighteen NP/HA hydrogel formulations. The NP/HA hydrogel platform demonstrates superior mechanical strength to HA-only hydrogels, susceptibility to oxidative/enzymatic degradation, and inherent cell-protective, antioxidant function. The performance of NP/HA hydrogels is shown to be affected by triblock architecture, guest/host grafting densities, and HA composition. In particular, the length of the hydrophilic second block and adamantane grafting density of self-assembled NPs significantly impacts hydrogel mechanical properties and shear-thinning behavior, while ROS-reactivity of poly(propylene sulfide) protects cells from cytotoxic ROS and reduces oxidative degradation of HA compared to HA-only hydrogels. This work provides insight into polymer structure-function considerations for designing hybrid NP/HA hydrogels and identifies antioxidant, shear-thinning hydrogels as promising injectable delivery platforms for small molecule drugs and therapeutic cells.

Green synthesis of chitosan–phytic acid polymers and nanoparticles

Herein, we aimed to synthesize and characterize chitosan (CS) and phytic acid (PA, CS–PA) polymers and nanoparticles for preparing materials with dye adsorption and drug delivery properties. Based on changes in the solution pH and the molecular weight and concentration of CS and PA, the CS–PA polymers and nanoparticles were prepared using a simple one-step ionic cross-linking protocol. CS–PA nanospheres formed polymers at high CS and PA concentrations, whereas CS–PA nanoparticles were formed at very low concentrations and under suitable pH conditions. Higher concentrations of the material produced denser polymers with a varied nanosphere size. Nanoparticles with different morphologies and sizes were obtained by changing the experimental conditions. Moreover, the self-aggregation of CS molecules in solution was reduced at low concentrations, allowing the easy formation of nanoparticles with regular morphological characteristics with PA. The nanoparticles exhibited good stability under specific conditions. The materials generated here showed promising application in dye adsorption and drug delivery field. This study provides clues for the construction and application of CS-based materials.

Gelatin methacrylate hydrogel with drug-loaded polymer microspheres as a new bioink for 3D bioprinting

3D bioprinted hydrogel constructs are advanced systems of a great drug delivery application potential. One of the bioinks that has recently gained a lot of attention is gelatin methacrylate (GelMA) hydrogel exhibiting specific properties, including UV cross-linking possibility. The present study aimed to develop a new bioink composed of GelMA and gelatin modified by addition of polymer (polycaprolactone or polyethersulfone) microspheres serving as bioactive substance carriers. The prepared microspheres suspension in GelMA/gelatin bioink was successfully bioprinted and subjected to various tests, which showed that the addition of microspheres and their type affects the physicochemical properties of the printouts. The hydrogel stability and structure was examined using scanning electron and optical microscopy, its thermal properties with differential scanning calorimetry and thermogravimetric analysis and its biocompatibility on HaCaT cells using viability assay and electron microscopy. Analyses also included tests of hydrogel equilibrium swelling ratio and release of marker substance. Subsequently, the matrices were loaded with ampicillin and the antibiotic release was validated by monitoring the antibacterial activity on Staphylococcus aureus and Escherichia coli. It was concluded that GelMA/gelatin bioink is a good and satisfying material for potential medical use. Depending on the polymer used, the addition of microspheres improves its structure, thermal and drug delivery properties.

Phototheranostic Nanoagents for Imaging‐Guided Treatment of Oral Cancer†

Comprehensive SummaryPhototherapy showed almost a lack of drug resistance and, depending on the therapeutic effects of non‐invasive light‐stimulating photosensors. The side effects of phototherapy were greatly reduced compared to their traditional equivalents. Phototheranostic nanoagents had new properties in drug delivery, biocompatibility, targeting and response, in which traditional phototheranostic drugs can not possess. Recently, a large number of relevant studies have demonstrated that photodynamic therapy (PDT) in combination with other agents and image‐guided multifunctional photothermal therapy (PTT) were well suited for the treatment of oral cancer. Through the design of the nanoagents, researchers have discovered various applications for phototherapy, such as targeted release of co‐packaged drugs, multifunctional imaging for diagnosis and treatment combination, accurate targeting caused by nanocarriers, and synergistic chemotherapy with phototherapy. In this paper, we first reviewed the research related to phototheranostic nanoagents for image‐guided treatment of oral cancer. We tried to introduce the design concept and the treatment effect by three parts of components of phototheranostic nanoagents, categories of phototheranostic nanoagents and application of phototheranostic nanoagents. It also provided a reference for nanomaterial development and clinical applications in research of oral cancer treatment.

Abstract 833: Exosomes isolation via lyophilization for Philadelphia-positive leukemia therapy

Abstract Background: Exosomes are extracellular vesicles having less than 200 nm size, secreted extracellularly by almost all types of cells. They regulate intercellular communication by delivering RNAi, proteins, viruses, and soluble factors as inherited payloads. In recent years, the application of exosomes to deliver small molecules have been widely investigated in tissue regeneration, therapeutics, as well as diagnostics. However, the isolation of exosomes has remained challenging mainly due to limitations of specialized instruments and the least cost-effective reagents. In this study, we developed a novel method to isolate exosomes from cultured cells. Experimental: The supernatant from cultured cells was collected and subjected to lyophilization after low-speed centrifugation. The characterization and quantification of exosomes were performed using Bradford assay. Scanning Electron Microscopy (SEM) and Nanoparticles Tracking Analysis (NTA) were carried out for shape and size distribution. Western blot was performed for the evaluation of the exosome specific surface markers (CD63, CD9, CD81, calnexin, HSP70, and TSG101). The as-isolated exosomes were loaded with commercial dyes (Cy5, Eosin) for the evaluation of their drug delivery properties. Furthermore, their drug loading and release were confirmed by loading tyrosine kinase inhibitors (TKIs) as a payload. Finally, the anti-leukemic drugs (dasatinib and ponatinib) were loaded on the isolated exosomes for targeting leukemia cell line i.e., K562 and BCR-ABL expressing Ba/F3 cells in in vitro model, using MTT assay for cell proliferation and Annexin-V/PI for apoptosis detection. Results: Here we found that the isolated exosomes have round shape with an average size of ~130 nm. They expressed known exosome markers including CD63, CD9, CD81, calnexin, HSP70, and TSG101. These exosomes could efficiently target and deliver dyes (Eosin and Cy5) and TKIs (dasatinib and ponatinib) to K562 and Ba/F3-cells expressing BCR-ABL. The TKIs-loaded exosomes inhibited the growth of leukemic cells and induced apoptosis in a dose dependent manner. Conclusion: We claim the development of a new method for active exosome isolation from cell culture. These exosomes could qualify for all the essential characterization, drug loading, and release ability by harnessing proliferation and inducing apoptosis in Ph+ leukemia cells. Citation Format: Fawad Ur Rehman, Rida e Maria Qazi, Zahra Sajid, Afsar Ali Mian. Exosomes isolation via lyophilization for Philadelphia-positive leukemia therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 833.

GLUT1 transporter-facilitated solid lipid nanoparticles loaded with anti-cancer therapeutics for ovarian cancer targeting

The therapeutics available for cancer treatment have the major hurdle of site-specific delivery of anti-cancer drugs to the tumor site and non-target specific side effects. The standard therapy for ovarian cancer still poses numerous pitfalls due to the irrational use of drugs affecting healthy cells. As an appealing approach, nanomedicine could revamp the therapeutic profile of anti-cancer agents. Owing to the low manufacturing cost, increased biocompatibility, and modifiable surface properties, lipid-based nanocarriers, particularly solid lipid nanoparticles (SLN), have remarkable drug delivery properties in cancer treatment. Given the extra-ordinary benefits, we developed anti-neoplastic (paclitaxel) drug-loaded SLN (PTX-SLN) and functionalized with N-acetyl-d-glucosamine (GLcNAc) (GLcNAc-PTX-SLN) to reduce the rate of proliferation, growth, and metastasis of ovarian cancer cells over-expressing GLUT1 transporters. The particles presented considerable size and distribution while demonstrating haemocompatibility. Using GLcNAc modified form of SLNs, confocal microscopy, MTT assay, and flow cytometry study demonstrated higher cellular uptake and significant cytotoxic effect. Also, molecular docking results established excellent binding affinity between GLcNAc and GLUT1, complimenting the feasibility of the therapeutic approach in targeted cancer therapy. Following the compendium of target-specific drug delivery by SLN, our results demonstrated a significant response for ovarian cancer therapy.

A novel TCR hydrogel wound dressing loaded with UC-SMC extract enhances skin regeneration and prevents wound scarring

Tissue fibrosis and scar formation are inevitable parts of wound healing in adult mammals, leading to a range of adverse outcomes including physical disability and psychological problems. In which, inflammation network plays a crucial role in this pathological process. Novel wound dressing materials with ideal biocompatibility, morphology adaptability, adequate mechanical strength, considerable wet-surface adhesion, and active drug delivery properties are urgently needed for clinical applications. In this study, umbilical cord mesenchymal stem cell extract (UC-SCE) was developed and verified for its ability to inhibit wound inflammation by driving macrophage polarization towards the anti-inflammatory (M2) phenotype and to promote wound tissue regeneration in SD rat wound model. Meanwhile, UC-SCE has also been shown to inhibit dermal fibroblast proliferation, migration and matrix production, and also to inhibit angiogenesis both in vitro and in vivo, and thus proving its anti-scarring capability. Furthermore, a novel dynamic-to-covalent hydrogel based on tandem crosslinking reaction (TCR) has been developed as a drug carrier for US-SCE delivery, which demonstrated suitable injectability, proper mechanical stability and excellent tissue adhesion. More importantly, when loaded with UC-SCE, this novel wound dressing was demonstrated able to regenerate wound tissue and inhibit hypertrophic scar formation in a rabbit ear scar model, thus principally proved the feasibility, efficacy and applicability of this novel SCE-hydrogel wound dressing for potential clinical translation.

Impact of dispersion media and carrier type on spray-dried proliposome powder formulations loaded with beclomethasone dipropionate for their pulmonary drug delivery via a next generation impactor.

Drug delivery via aerosolization for localized and systemic effect is a non-invasive approach to achieving pulmonary targeting. The aim of this study was to prepare spray-dried proliposome (SDP) powder formulations to produce carrier particles for superior aerosolization performance, assessed via a next generation impactor (NGI) in combination with a dry powder inhaler. SDP powder formulations (F1-F10) were prepared using a spray dryer, employing five different types of lactose carriers (Lactose monohydrate (LMH), lactose microfine (LMF), lactose 003, lactose 220 and lactose 300) and two different dispersion media. The first dispersion medium was comprised of water and ethanol (50:50% v/v ratio), and the second dispersion medium comprised wholly of ethanol (100%). In the first dispersion medium, the lipid phase (consisting of Soya phosphatidylcholine (SPC as phospholipid) and Beclomethasone dipropionate (BDP; model drug) were dissolved in ethanol and the lactose carrier in water, followed by spray drying. Whereas in second dispersion medium, the lipid phase and lactose carrier were dispersed in ethanol only, post spray drying. SDP powder formulations (F1-F5) possessed significantly smaller particles (2.89 ± 1.24-4.48 ± 1.20 μm), when compared to SDP F6-F10 formulations (10.63 ± 3.71-19.27 ± 4.98 μm), irrespective of lactose carrier type via SEM (scanning electron microscopy). Crystallinity of the F6-F10 and amorphicity of F1-F15 formulations were confirmed by XRD (X-ray diffraction). Differences in size and crystallinity were further reflected in production yield, where significantly higher production yield was obtained for F1-F5 (74.87 ± 4.28-87.32 ± 2.42%) then F6-F10 formulations (40.08 ± 5.714-54.98 ± 5.82%), irrespective of carrier type. Negligible differences were noted in terms of entrapment efficiency, when comparing F1-F5 SDP formulations (94.67 ± 8.41-96.35 ± 7.93) to F6-F10 formulations (78.16 ± 9.35-82.95 ± 9.62). Moreover, formulations F1-F5 demonstrated significantly higher fine particle fraction (FPF), fine particle dose (FPD) and respirable fraction (RF) (on average of 30.35%, 890.12 μg and 85.90%) when compared to counterpart SDP powder formulations (F6-F10). This study has demonstrated that when a combination of water and ethanol was employed as dispersion medium (formulations F1-F5), superior formulation properties for pulmonary drug delivery were observed, irrespective of carrier type employed.

Facile synthesis of nanofibrous and hollow titania microspheres as drug‐laden cell carriers

AbstractMicrospheres are one type of promising cell‐supporting matrices. However, the synthesis of nanofibrous and hollow microspheres as drug‐laden cell carriers is still a great challenge. Here, the nanofibrous and hollow titania nanowire (NH‐TiNW) microspheres were synthesized by in situ alkali hydrothermal treatment of hollow titania (H‐Ti) microspheres, and their microstructure, biocompatibility, and drug delivery property were evaluated. By controlling hydrothermal temperature from 80 to 120°C and hydrothermal time from 1 to 4 h, the surface of H‐Ti microspheres was controllably tailored with nanoparticles and NWs. The results showed that NH‐TiNW microspheres were spherical in morphology with a diameter of 100–200 µm, hierarchically assembled by numerous TiNWs with the diameter of 10–20 nm, and possessed a nanofibrous and hollow structure. In vitro biocompatibility evaluation showed that NH‐TiNW microspheres presented an enhanced cell attachment and proliferation compared with H‐Ti microspheres due to the presence of the nanofibrous surface. Drug delivery evaluation showed that NH‐TiNW microspheres strongly adsorbed tetracycline hydrochloride (one type of antibiotic, model drug) with a loading efficiency of 81.5% ± 1% due to the presence of the nanofibrous and hollow structure and also effectively maintained the biological efficiency of the loaded drugs to inhibit the growth of bacteria.

Impact of active sites on encapsulation of curcumin in Metal Organic Frameworks

In this study, we present the investigation of the curcumin loading and release properties of four different Metal-Organic Frameworks (MOFs) with varying metal centres and organic ligands. Through our research, we have identified HKUST-1 and MIL-100, highly porous copper and iron-containing MOFs, that exhibit specific interactions with curcumin, leading to high encapsulation efficiencies (55%–75%) even at low concentrations as 6 ppm. The binding modes of curcumin onto MOFs have been investigated using a combined experimental and computational approach. Furthermore, our drug-releasing studies have revealed slow and prolonged release for over two days, which further indicates the specific interactions of curcumin with HKUST-1 and MIL-100. To the best of our knowledge, this is the first comparative study that investigates the drug delivery properties of curcumin using Copper, Ferrous, and Zinc MOFs. Our findings pave the way for the development of stable, highly interactive MOFs as drug carriers for curcumin, which has the potential to overcome its poor aqueous solubility and rapid metabolism, and enhance its pharmacological activities in medicine.

Hybrid extracellular vesicles for drug delivery

Extracellular vesicles (EVs) are expected to serve as interesting drug delivery vectors as they may offer unique and new properties for drug delivery. Their natural origin, protein and nucleic acid composition, and intrinsic pleiotropic therapeutic effects could enable new possibilities in the field of drug delivery. Here, we aimed to review the methods used to produce Hybrid EVs, a recently emerged type of EV-based vector made from both EVs and synthetic vectors to exploit their respective properties. Hybrid EV/synthetic objects can be obtained by incubation, electrostatic interactions, polyethylene glycol (PEG)-mediated fusion, co-extrusion, freeze-thawing, or simple EV surface modification, leading to different types of objects. We also opted to review the properties of these vectors, and specifically compared them with those of other drug delivery vectors. It has to be noticed that only a limited number of study report loading metrics that allow cross article comparison. Based on this critical analysis, we attempted to draw the pith and marrow from these relatively difficult-to-compare studies and integrate them into the more general context of opportunities in drug delivery and drug development, with a particular focus on oncology.

Synthesis of Magnetic Iron Oxide-Incorporated Cellulose Composite Particles: An Investigation on Antioxidant Properties and Drug Delivery Applications.

In recent years, polymer-supported magnetic iron oxide nanoparticles (MIO-NPs) have gained a lot of attention in biomedical and healthcare applications due to their unique magnetic properties, low toxicity, cost-effectiveness, biocompatibility, and biodegradability. In this study, waste tissue papers (WTP) and sugarcane bagasse (SCB) were utilized to prepare magnetic iron oxide (MIO)-incorporated WTP/MIO and SCB/MIO nanocomposite particles (NCPs) based on in situ co-precipitation methods, and they were characterized using advanced spectroscopic techniques. In addition, their anti-oxidant and drug-delivery properties were investigated. Field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD) analyses revealed that the shapes of the MIO-NPs, SCB/MIO-NCPs, and WTP/MIO-NCPs were agglomerated and irregularly spherical with a crystallite size of 12.38 nm, 10.85 nm, and 11.47 nm, respectively. Vibrational sample magnetometry (VSM) analysis showed that both the NPs and the NCPs were paramagnetic. The free radical scavenging assay ascertained that the WTP/MIO-NCPs, SCB/MIO-NCPs, and MIO-NPs exhibited almost negligible antioxidant activity in comparison to ascorbic acid. The swelling capacities of the SCB/MIO-NCPs and WTP/MIO-NCPs were 155.0% and 159.5%, respectively, which were much higher than the swelling efficiencies of cellulose-SCB (58.3%) and cellulose-WTP (61.6%). The order of metronidazole drug loading after 3 days was: cellulose-SCB < cellulose-WTP < MIO-NPs < SCB/MIO-NCPs < WTP/MIO-NCPs, whereas the sequence of the drug-releasing rate after 240 min was: WTP/MIO-NCPs < SCB/MIO-NCPs < MIO-NPs < cellulose-WTP < cellulose-SCB. Overall, the results of this study showed that the incorporation of MIO-NPs in the cellulose matrix increased the swelling capacity, drug-loading capacity, and drug-releasing time. Therefore, cellulose/MIO-NCPs obtained from waste materials such as SCB and WTP can be used as a potential vehicle for medical applications, especially in a metronidazole drug delivery system.

Synthetic and Natural Polymeric Drug Delivery Systems - A Comprehensive Overview of Polycaprolactone and Glucan Particles

The small size and large surface area of nano and microparticles are interesting properties for drug delivery, hypothetically capable of overcoming some limitations of conventional therapeutic medicine and diagnostic agents. Although their features are highly influenced by the polymer characteristics, these particles are known for encapsulating high amounts of drugs, improving their stability and bioavailability and enabling different administration routes. Among synthetic polymers, polycaprolactone (PCL) nanoparticles are widely studied in drug delivery due to the polymer excellent biocompatibility and degradability and for its ability to blend with other polymers. On its turn, among natural polymers, glucan has been emerging as a promising candidate for drug delivery particularly due to structure forming abilities and its immunomodulatory effects. Under the safe-by-design approach for the development of polymeric particles, this review encloses a comprehensive summary of production methods, physicochemical characteristics and immunotoxicity profiles of PCL and glucan particles developed for drug delivery.

Sol-Gel Synthesis of Caffeic Acid Entrapped in Silica/Polyethylene Glycol Based Organic-Inorganic Hybrids: Drug Delivery and Biological Properties

The failure of medical devices, such as bones prosthesis, is mainly due to inflammatory and infectious phenomena. Entrapping anti-inflammatory and antimicrobial agents inside the biomaterial matrix could avoid these phenomena. In this context, inorganic/organic silica (S)/polyethylene glycol (P)/caffeic acid (A) hybrid systems were synthesized via the sol-gel method with different weight percentages of P and A. Fourier-transform infrared (FT-IR) revealed that caffeic acid undergoes an oxidizing phenomenon in the sol-gel synthesis condition. Additionally, the formation of a hydroxyapatite layer on hybrid surfaces was demonstrated by employing the Kokubo test and analyzing the samples using scanning electron microscopy, X-ray diffraction, and FT-IR. Moreover, further characterization of the antimicrobial activity of the synthesized biomaterials was carried out using the Kirby–Bauer test. Finally, UV-Vis measurement was useful to evaluate the caffeic acid kinetic release in simulated body fluid (SBF) at 37 °C. The kinetic study disclosed that the hybrid materials without polyethylene glycol had faster release rates than the ones obtained without the organic polymer.

Bench-to-bedside: Feasibility of nano-engineered and drug-delivery biomaterials for bone-anchored implants and periodontal applications.

Nanotechnology and drug-release biomaterials have been thoroughly explored in the last few years aiming to develop specialized clinical treatments. However, it is rare to find biomaterials associated with drug delivery properties in the current dental market for application in oral bone- and periodontal-related procedures. The gap between basic scientific evidence and translation to a commercial product remains wide. Several challenges have been reported regarding the clinical translation of biomaterials with drug-delivery systems (BDDS) and nanofeatures. Therefore, processes for BDDS development, application in preclinical models, drug delivery doses, sterilization processes, storage protocols and approval requirements were explored in this review, associated with tentative solutions for these issues. The diversity of techniques and compounds/molecules applied to develop BDDS demands a case-by-case approach to manufacturing and validating a commercial biomaterial. Promising outcomes such as accelerated tissue healing and higher antibacterial response have been shown through basic and preclinical studies using BDDS and nano-engineered biomaterials; however, the adequate process for sterilization, storage, cost-effectiveness and possible cytotoxic effects remains unclear for multifunctional biomaterials incorporated with different chemical compounds; then BDDSs are rarely translated into products. The future benefits of BDDS and nano-engineered biomaterials have been reported suggesting personalized clinical treatment and a promising reduction in the use of systemic antibiotics. Finally, the launch of these specialized biomaterials with solid data and controlled traceability onto the market will generate strong specificity for healthcare treatments.

DUCNP@Mn-MOF/FOE as a Highly Selective and Bioavailable Drug Delivery System for Synergistic Combination Cancer Therapy.

Heterostructures comprising lanthanide-doped upconversion nanoparticles (DUCNPs) and metal-organic frameworks (MOFs) are emerging as promising nanosystems for integrating medical diagnosis and treatment. Here, the DUCNP@Mn-MOF nanocarrier was developed, which showed good efficiency for loading and delivering a cytotoxic antitumor agent (3-F-10-OH-evodiamine, FOE). The combined advantages of the pH-responsive and peroxidase-like properties of Mn-MOF and the unique optical features of DUCNPs granted the DUCNP@Mn-MOF/FOE system synergistic chemodynamic and chemotherapeutic effects. The DUCNP@Mn-MOF nanocarrier effectively overcame the intrinsic limitations of FOE, such as its unfavorable physicochemical properties and limited in vivo potency. This complexed nanosystem was responsive to the tumor microenvironment and showed excellent tumor targeting capability. Thus, DUCNP@Mn-MOF/FOE exhibited highly selective and bioavailable drug delivery properties and is promising for cancer therapy. In a mouse breast cancer model, DUCNP@Mn-MOF/FOE inhibited tumor growth without significant toxicity. Therefore, the proposed nanosystem represents a promising theragnostic platform for multimodal combination diagnosis and therapy of tumors.

Identification of Nanoparticle Properties for Optimal Drug Delivery across a Physiological Cell Barrier.

Nanoparticles (NPs) represent an attractive strategy to overcome difficulties associated with the delivery of therapeutics. Knowing the optimal properties of NPs to address these issues could allow for improved in vivo responses. This work investigated NPs prepared from 5 materials of 3 sizes and 3 concentrations applied to a cell barrier model. The NPs permeability across a cell barrier and their effects on cell barrier integrity and cell viability were evaluated. The properties of these NPs, as determined in water (traditional) vs. media (realistic), were compared to cell responses. It was found that for all cellular activities, NP properties determined in media was the best predictor of the cell response. Notably, ZnO NPs caused significant alterations to cell viability across all 3 cell lines tested. Importantly, we report that the zeta potential of NPs correlates significantly with NP permeability and NP-induced changes in cell viability. NPs with physiological-based zeta potential of -12 mV result in good cell barrier penetration without considerable changes in cell viability.