Advanced 3D Electrospinning "Xspin" System: Fabrication of Bifiber Floating Oral Pharmaceutical Scaffolds for Controlled Drug Delivery.

Electrospinning has become a widely used and efficient method for manufacturing nanofibers from diverse polymers. This study introduces an advanced electrospinning technique, Xspin - a multi-functional 3D printing platform coupled with electrospinning system, integrating a customised 3D printhead, MaGIC - Multi-channeled and Guided Inner Controlling printheads. The Xspin system represents a cutting-edge fusion of electrospinning and 3D printing technologies within the realm of pharmaceutical sciences and biomaterials. This innovative platform excels in the production of novel fiber with various materials and allows for the creation of highly customized fiber structures, a capability hitherto unattainable through conventional electrospinning methodologies. By integrating the benefits of electrospinning with the precision of 3D printing, the Xspin system offers enhanced control over the scaffold morphology and drug release kinetics. Herein, we fabricated a model floating pharmaceutical dosage for the dual delivery of curcumin and ritonavir and thoroughly characterized the product. Fourier transform infrared (FTIR) spectroscopy demonstrated that curcumin chemically reacted with the polymer during the Xspin process. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the solid-state properties of the active pharmaceutical ingredient after Xspin processing. Scanning electron microscopy (SEM) revealed the surface morphology of the Xspin-produced fibers, confirming the presence of the bifiber structure. To optimize the quality and diameter control of the electrospun fibers, a design of experiment (DoE) approach based on quality by design (QbD) principles was utilized. The bifibers expanded to approximately 10-11 times their original size after freeze-drying and effectively entrapped 87% curcumin and 84% ritonavir. In vitro release studies demonstrated that the Xspin system released 35% more ritonavir than traditional pharmaceutical pills in 2 h, with curcumin showing complete release in pH 1.2 in 5 min, simulating stomach media. Furthermore, the absorption rate of curcumin was controlled by the characteristics of the linked polymer, which enables both drugs to be absorbed at the desired time. Additionally, multivariate statistical analyses (ANOVA, pareto chart, etc.) were conducted to gain better insights and understanding of the results such as discern statistical differences among the studied groups. Overall, the Xspin system shows significant potential for manufacturing nanofiber pharmaceutical dosages with precise drug release capabilities, offering new opportunities for controlled drug delivery applications.

Pluronic F127-Complexed PEGylated Poly(glutamic acid)-Cisplatin Nanomedicine for Enhanced Glioblastoma Therapy.

Glioblastoma is one of the most aggressive and treatment-resistant forms of primary brain cancer, posing significant challenges in effective therapy. This study aimed to enhance the effectiveness of glioblastoma therapy by developing a unique nanomedicine composed of Pluronic F127-complexed PEGylated poly(glutamic acid)-cisplatin (PLG-PEG/PF127-CDDP). PLG-PEG/PF127-CDDP demonstrated an optimal size of 133.97 ± 12.60 nm, facilitating efficient cell uptake by GL261 glioma cells. In vitro studies showed significant cytotoxicity against glioma cells with a half-maximal (50%) inhibitory concentration (IC50) of 12.61 µg mL-1 at 48 h and a 72.53% ± 1.89% reduction in cell invasion. Furthermore, PLG-PEG/PF127-CDDP prolonged the circulation half-life of cisplatin to 9.75 h in vivo, leading to a more than 50% reduction in tumor size on day 16 post-treatment initiation in a murine model of glioma. The treatment significantly elevated lactate levels in GL261 cells, indicating enhanced metabolic disruption. Therefore, PLG-PEG/PF127-CDDP offers a promising approach for glioblastoma therapy due to its effects on improving drug delivery efficiency, therapeutic outcomes, and safety while minimizing systemic side effects. This work underscores the potential of polymer-based nanomedicines in overcoming the challenges of treating brain tumors, paving the way for future clinical applications.

Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone electrospun scaffolds accelerate burn wound healing.

Wound healing is a complex process involving multiple independent and overlapping sequential physiological mechanisms. In addition to cutaneous injury, a severe burn stimulates physiological derangements that induce a systemic hypermetabolic response resulting in impaired wound healing. Topical application of the anti-androgen drug, flutamide accelerates cutaneous wound healing, whereas paradoxically systemic dihydrotestosterone (DHT) improves burn wound healing. We developed and characterized a PCL scaffold that is capable of controlled release of androgen (DHT) and anti-androgen (F) individually or together. This study aims to investigate whether local modification of androgen actions has an impact on burn injury wound healing. In a full-thickness burn wound healing, mouse model, DHT/F-scaffold showed a significantly faster wound healing compared with F-scaffold or DHT-scaffold. Histology analysis confirmed that DHT/F-scaffold exhibited higher re-epithelization, cell proliferation, angiogenesis, and collagen deposition. Dual release of DHT and F from PCL scaffolds promoted cell proliferation of human keratinocytes and alters the keratinocyte cell cycle. Lastly, no adverse effects on androgen-dependent organs, spleen and liver were observed. In conclusion, we demonstrated DHT plus F load PCL scaffolds accelerated burn wound healing when loading alone did not. These findings point to a complex role of androgens in burn wound healing and open novel therapeutic avenues for treating severe burn patients.

Rational Understanding of Loading and Release of Doxorubicin by UV-Light- and pH-Responsive Poly(NIPAM-co-SPMA) Micelle-like Aggregates.

A deep understanding of the interactions between micelle-like aggregates and antineoplastic drugs is paramount to control their adequate delivery. Herein, Poly(NIPAM-co-SPMA) copolymer nanocarriers were synthesized according to our previous published methodology, and the loading and release of poorly and highly water-soluble doxorubicin forms (Dox and Dox-HCl, respectively) were evaluated upon UV light irradiation and pH-variation stimuli. Capillary electrophoresis (CE) coupled to a fluorescence detector (LIF) allowed us to specifically characterize these systems and deeply study the loading and release processes. For this purpose, varying concentrations of doxorubicin were tested, and the loading/release rates were indirectly quantified thanks to the "free" doxorubicin concentration in solution. This study highlighted that Dox loading (9.4 µg/mg) was more effective than Dox-HCl loading (5.5 µg/mg). In contrast, 68 and 74% of Dox-HCl were respectively released after 2 min upon pH variation (from 7.4 to 6.0) and combined UV + pH 6.0 stimuli, while only 27% of Dox was invariably released upon application of the same stimuli. These results are coherent with the characteristics of both DoxHCl and Dox: Electrostatic interactions between Dox-HCl and the micelle-membrane structure (NIPAM) seemed predominant, while hydrophobic interactions were expected between Dox and the SP moieties at the inner part of the micelle-like aggregate, leading to different behaviors in both loading and release of the two doxorubicin forms. For doxorubicin loading concentrations higher than 3 µM, the electrophoretic profiles presented an additional peak. Thanks to CE characterizations, this peak was attributed to the formation of a complex formed between the nonaggregated copolymer and the doxorubicin molecules. This report therefore undergoes deep characterization of the dynamic formation of different micelle/drug complexes involved in the global drug-delivery behavior and therefore contributes to the development of more effective stimuli-responsive nanocarriers.

Layered double hydroxides - poloxamer 188 nanocomposites based on exfoliation reassembling for improved cellular uptake and controlled delivery of methotrexate.

Exploitation of advanced methotrexate (MTX) delivery with nanocomposites has important clinical application value. Poloxamer 188 micelle and layered double hydroxide loaded with MTX (LDH-MTX) by exfoliation reassembling were used to prepare LDH-MTX-poloxamer 188 nanocomposites with good dispersibility and efficient cellular uptake for controlled drug delivery. The LDH-MTX-poloxamer 188 nanocomposites with sphere-like morphology, of which the average hydrodynamic diameter was <100 nm, were shown to have better dispersion state than naked LDH-MTX. Importantly, the LDH-MTX-poloxamer 188 nanocomposites could achieve significant sustained drug release and have obvious pH dependent responsive release ability. In addition, these nanocomposites also exhibited long-term and excellent in vitro antitumor efficacy as opposed to pure MTX or LDH-MTX as evident from cell viability. More interestingly, compared to pure FITC used to simulate MTX, LDH nanocomposites labeled with FITC were considered to have better cell adhesion through cell uptake. Therefore, the studied nanocomposites of LDH-MTX-poloxamer 188 can be further used as a new advanced MTX delivery nanovehicles with desired properties in future therapeutic aspects.

Nanoparticles guided drug delivery and imaging in gastric cancer.

Gastric cancer represents a deadly malignancy worldwide, yet current therapeutic regimens remain ineffective. Nanoparticle (NP) -based solutions could allow the design of novel therapeutic methods to eliminate this fatal disease. NPs typically carry out a significant role in multifunctional, multimodal imaging, and drug delivery carriers. In the recent decade, they have emerged as candidate approaches for the design of novel treatment strategies. Tumor nanotherapeutics characteristically possess various distinct advantages compared to conventional anti-cancer medications, which suffer from nonspecific bio-distribution, low solubility, and poor bioavailability. In this review, we will discuss the application of NPs in diagnosis and controlled drug delivery in gastric cancer (GC). We will focus on various NPs-based strategies employed against GC.

Thermal-Responsive MXene-DNA Hydrogel for Near-Infrared Light Triggered Localized Photothermal-Chemo Synergistic Cancer Therapy.

Stimuli-responsive DNA hydrogels are promising candidates for cancer treatment, as they not only possess biocompatible and biodegradable 3D network structures as highly efficient carriers for therapeutic agents but also are capable of undergoing programmable gel-to-solution transition upon external stimuli to achieve controlled delivery. Herein, a promising platform for highly efficient photothermal-chemo synergistic cancer therapy is established by integrating DNA hydrogels with Ti3 C2 TX -based MXene as a photothermal agent and doxorubicin (DOX) as a loaded chemotherapeutic agent. Upon the irradiation of near-infrared light (NIR), temperature rise caused by photothermal MXene nanosheets triggers the reversible gel-to-solution transition of the DOX-loaded MXene-DNA hydrogel, during which the DNA duplex crosslinking structures unwind to release therapeutic agents for efficient localized cancer therapy. Removal of the NIR irradiation results in the re-formation of DNA duplex structures and the hydrogel matrix, and the recombination of free DOX and adaptive hydrogel transformations can also be achieved. As demonstrated by both in vitro and in vivo models, the MXene-DNA hydrogel system, with excellent biocompatibility and injectability, dynamically NIR-triggered drug delivery, and enhanced drug uptake under mild hyperthermia conditions, exhibits efficient localized cancer treatment with fewer side effects to the organisms.

Recent progress in advanced biomaterials for long-acting reversible contraception.

Unintended pregnancy is a global issue with serious ramifications for women, their families, and society, including abortion, infertility, and maternal death. Although existing contraceptive strategies have been widely used in people's lives, there have not been satisfactory feedbacks due to low contraceptive efficacy and related side effects (e.g., decreased sexuality, menstrual cycle disorder, and even lifelong infertility). In recent years, biomaterials-based long-acting reversible contraception has received increasing attention from the viewpoint of fundamental research and practical applications mainly owing to improved delivery routes and controlled drug delivery. This review summarizes recent progress in advanced biomaterials for long-acting reversible contraception via various delivery routes, including subcutaneous implant, transdermal patch, oral administration, vaginal ring, intrauterine device, fallopian tube occlusion, vas deferens contraception, and Intravenous administration. In addition, biomaterials, especially nanomaterials, still need to be improved and prospects for the future in contraception are mentioned.

Design, development and characterization of interpenetrating polymer network hydrogel bead for controlled release of glipizide drug.

In the current study, a novel interpenetrating polymer network (IPN) hydrogel bead was developed by encapsulation of antidiabetic drug glipizide using sodium alginate (SAL) and xanthan gum (XAG) biopolymers by ionotropic gelation technique with calcium chloride as cross-linking agent. In light of the fact that IPN hydrogel beads possess greater benefits in controlling the release of such short acting drug, sodium alginate and xanthan gum IPN hydrogel beads were prepared at different mass ratios (SAL:XAG = 10:0, 9:1, 8:2, 7:3, 6:4, 5:5). Similarly, drug-loaded IPN hydrogel beads were also developed. The prepared hydrogel beads were investigated using Fourier transform infrared spectroscopy, X-ray powder diffraction, and thermogravimetric studies to understand the type of interactions between the composite beads. Surface morphology changes were studied by scanning electron microscopy. The particle size, drug entrapment efficiency, and swelling behavior of prepared hydrogel beads were also studied. Based on in vitro drug dissolution studies, it was observed that SXF4 preparation containing SAL and XAG polymers at 7:3 ratio showed extended drug release of 97.53% at 9 h. This study demonstrated that inclusion of XAG has extended the drug release and able to achieve zero-order drug release profile.

Role of Polymer Concentration and Crosslinking Density on Release Rates of Small Molecule Drugs.

Over the past few years, researchers have demonstrated the use of hydrogels to design drug delivery platforms that offer a variety of benefits, including but not limited to longer circulation times, reduced drug degradation, and improved targeting. Furthermore, a variety of strategies have been explored to develop stimulus-responsive hydrogels to design smart drug delivery platforms that can release drugs to specific target areas and at predetermined rates. However, only a few studies have focused on exploring how innate hydrogel properties can be optimized and modulated to tailor drug dosage and release rates. Here, we investigated the individual and combined roles of polymer concentration and crosslinking density (controlled using both chemical and nanoparticle-mediated physical crosslinking) on drug delivery rates. These experiments indicated a strong correlation between the aforementioned hydrogel properties and drug release rates. Importantly, they also revealed the existence of a saturation point in the ability to control drug release rates through a combination of chemical and physical crosslinkers. Collectively, our analyses describe how different hydrogel properties affect drug release rates and lay the foundation to develop drug delivery platforms that can be programmed to release a variety of bioactive payloads at defined rates.

Carboxymethyl-Dextran-Coated Superparamagnetic Iron Oxide Nanoparticles for Drug Delivery: Influence of the Coating Thickness on the Particle Properties.

Carboxymethyl-dextran (CMD)-coated iron oxide nanoparticles (IONs) are of great interest in nanomedicine, especially for applications in drug delivery. To develop a magnetically controlled drug delivery system, many factors must be considered, including the composition, surface properties, size and agglomeration, magnetization, cytocompatibility, and drug activity. This study reveals how the CMD coating thickness can influence these particle properties. ION@CMD are synthesized by co-precipitation. A higher quantity of CMD leads to a thicker coating and a reduced superparamagnetic core size with decreasing magnetization. Above 12.5−25.0 g L−1 of CMD, the particles are colloidally stable. All the particles show hydrodynamic diameters < 100 nm and a good cell viability in contact with smooth muscle cells, fulfilling two of the most critical characteristics of drug delivery systems. New insights into the significant impact of agglomeration on the magnetophoretic behavior are shown. Remarkable drug loadings (62%) with the antimicrobial peptide lasioglossin and an excellent efficiency (82.3%) were obtained by covalent coupling with the EDC/NHS (N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) method in comparison with the adsorption method (24% drug loading, 28% efficiency). The systems showed high antimicrobial activity with a minimal inhibitory concentration of 1.13 µM (adsorption) and 1.70 µM (covalent). This system successfully combines an antimicrobial peptide with a magnetically controllable drug carrier.

Novel Tumor-Targeting Nanoparticles for Cancer Treatment-A Review.

Being one of the leading causes of death and disability worldwide, cancer represents an ongoing interdisciplinary challenge for the scientific community. As currently used treatments may face limitations in terms of both efficiency and adverse effects, continuous research has been directed towards overcoming existing challenges and finding safer specific alternatives. In particular, increasing interest has been gathered around integrating nanotechnology in cancer management and subsequentially developing various tumor-targeting nanoparticles for cancer applications. In this respect, the present paper briefly describes the most used cancer treatments in clinical practice to set a reference framework for recent research findings, further focusing on the novel developments in the field. More specifically, this review elaborates on the top recent studies concerning various nanomaterials (i.e., carbon-based, metal-based, liposomes, cubosomes, lipid-based, polymer-based, micelles, virus-based, exosomes, and cell membrane-coated nanomaterials) that show promising potential in different cancer applications.

Development of Genistein Drug Delivery Systems Based on Bacterial Nanocellulose for Potential Colorectal Cancer Chemoprevention: Effect of Nanocellulose Surface Modification on Genistein Adsorption.

Genistein is an isoflavone with antioxidant, anti-inflammatory, and anticancer properties. That said, its use in the industry is limited by its low solubility in aqueous systems. In this work, bacterial nanocellulose (BNC) and BNC modified with cetyltrimethylammonium (BNC-CTAB) were evaluated as genistein-encapsulating materials for their controlled release in cancer chemoprevention. Thin films were obtained and characterized by contact angle, AFM, TEM, UV-Vis spectroscopy FTIR, and TGA techniques to verify surface modification and genistein encapsulation. The results show a decrease in hydrophilization degree and an increase in diameter after BNC modification. Furthermore, the affinity of genistein with the encapsulating materials was determined in the context of monolayer and multilayer isotherms, thermodynamic parameters and adsorption kinetics. Spontaneous, endothermic and reversible adsorption processes were found for BNC-GEN and BNC-CTAB-GEN. After two hours, the maximum adsorption capacity corresponded to 4.59 mg GEN∙g-1 BNC and 6.10 mg GEN∙g-1 BNC-CTAB; the latter was a more stable system. Additionally, in vitro release assays performed with simulated gastrointestinal fluids indicated controlled and continuous desorption in gastric and colon fluids, with a release of around 5% and 85%, respectively, for either system. Finally, the IC50 tests made it possible to determine the amounts of films required to achieve therapeutic concentrations for SW480 and SW620 cell lines.

Magnetic Targeting of 5-Fluorouracil-Loaded Liposome-Nanogels for In Vivo Breast Cancer Therapy and the Cytotoxic Effects on Liver and Kidney.

In our previous paper, we demonstrated the ex vivo studies of non-toxic liposome-nanogel systems by which the long-term drug release could be provided from hybrid systems for the 5-fluorouracil (5-FU) drug molecule. The aim of this study was the in vivo magnetic targeting of 5-FU-loaded Fe3O4 nanoparticles including DPPC liposome-based PEGylated nanogels (5-FU loaded Fe3O4LPN) to breast cancer tissue and the investigation of the treatment and cytotoxic effects of that hybrid system to the liver and kidney in CD-1 mice using an external magnetic field. The effectiveness of the control, 5-FU group, Fe3O4LPN, and 5-FU-loaded Fe3O4LPN systems was evaluated using histopathology in terms of p53, ESR, PRG and C-erB-2, and qRT-PCR in terms of TYMS, ESR-1, RPG, and EGRF. Also, the cytotoxicity was analyzed by histopathological evaluation of kidney and liver tissues. Caspase-3 and caspase-9 evaluations were performed by qRT-PCR. The creatinine and ALT levels were also evaluated by comparing the blood samples of all groups. A total of 300-nm TEM-sized Fe3O4LNP hybrid system was successfully prepared. That system significantly decreased the TYMS and ESR1 levels after treatment process and increased the levels of p53 expression. The levels of caspase-3 mRNA did not change during the treatment, but the level of caspase-9 mRNA level was significantly decreased. The magnetically targeted liposome-based nanogel hybrid system is promising an effective therapy for the breast tumor with less liver and kidney damage. This Fe3O4LNP hybrid system could be useful for the similar small molecules.

A New Insight to Silver Sulfadiazine Antibacterial Dressings: Nanoparticle-Loaded Nanofibers for Controlled Drug Delivery.

The aim of this study was formulating a new-generation antibacterial dressing in a form of polymer-based hybrid nanofiber-nanoparticles, effective on Gram-negative and Gram-positive bacteria using silver sulfadiazine (SSD), an FDA-approved topical antibiotic. In this study, SSD nanoparticles were prepared with chitosan for taking the advantage of antibacterial and wound healing properties. Chitosan nanoparticles of SSD were prepared by using tripolyphosphate (TPP) or sulfobutylether-ß-cyclodextrin (SBE-ß-CD) as crosslinkers via ionic gelation method and then loaded to PVP-K30 and PVP-K90 nanofibers to obtain polymer-based nanofiber-nanoparticles. SSD-loaded chitosan nanoparticles prepared with SBE-ß-CD had lower particle size (359.6 ± 19.9 nm) and polydispersity index (0.364 ± 0.113) as well, indicating a more desired particle size distribution but lower encapsulation efficiency (56.04% ± 4.33). It was found that loading drug in SBE-ß-CD crosslinked nanoparticles and dispersing in nanofiber matrix lowered SSD release compared to  TPP crosslinked nanoparticle-loaded nanofibers. Drug release obtained by both TPP or SBE-ß-CD crosslinked nanoparticle-loaded PVP-K30 nanofibers is significantly higher than nanoparticle-loaded PVP-K90 nanofibers, indicating that SSD release was mainly affected by polymer type. SSD nanoparticle-loaded PVP-K30 nanofibers were found to be effective against Gram-negative (Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii) and Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis). SSD release was sustained by PVP-K90, resulting in lower antibacterial efficiency especially against Gram-positive bacteria. PVP-K30-based nanofiber-CS nanoparticle hybrids offer a new platform by combining and improving advantages of nanofibers and nanoparticles for obtaining controlled drug release and antibacterial efficacy.

Versatile Nanoscale Metal-Organic Frameworks (nMOFs): An Emerging 3D Nanoplatform for Drug Delivery and Therapeutic Applications.

For decades, nanoscale metal-organic frameworks (nMOFs) have attracted extensive interest in biomedicine due to their distinct characteristics, including facile synthesis, porous interior, and tunable biocompatibility. With high porosity, versatile nMOFs allow for the facile encapsulation of various therapeutic agents with exceptionally high payloads. Constructed from metal ions and organic linkers through coordination bonds, nMOFs with plentiful functional groups enable the surface modification for active targeting and enhanced biocompatibility. This review outlines the up-to-date progresses on the exploration of nMOFs in the field of biomedicine. First, the classification and synthesis of nMOFs are discussed, followed by the concrete introduction of drug loading strategies of nMOFs and mechanisms of stimulation-responsive drug release. Second, the smart designs of the nMOFs-based platforms for anticancer and antibacterial treatment are summarized. Finally, the basic challenges faced by nMOFs research and the great potential of biomimetic nMOFs are presented. This review article affords an inspiring insight into the interdisciplinary research of nMOFs and their biomedical applications, which holds great expectation for their further clinical translation.

Layer-by-Layer Biomaterials for Drug Delivery.

Controlled drug delivery formulations have revolutionized treatments for a range of health conditions. Over decades of innovation, layer-by-layer (LbL) self-assembly has emerged as one of the most versatile fabrication methods used to develop multifunctional controlled drug release coatings. The numerous advantages of LbL include its ability to incorporate and preserve biological activity of therapeutic agents; coat multiple substrates of all scales (e.g., nanoparticles to implants); and exhibit tuned, targeted, and/or responsive drug release behavior. The functional behavior of LbL films can be related to their physicochemical properties. In this review, we highlight recent advances in the development of LbL-engineered biomaterials for drug delivery, demonstrating their potential in the fields of cancer therapy, microbial infection prevention and treatment, and directing cellular responses. We discuss the various advantages of LbL biomaterial design for a given application as demonstrated through in vitro and in vivo studies.

MTX-Loaded Dual Thermoresponsive and pH-Responsive Magnetic Hydrogel Nanocomposite Particles for Combined Controlled Drug Delivery and Hyperthermia Therapy of Cancer.

In recent years, the exploitation of magnetic nanoparticles in smart polymeric matrices have received increased attention in several fields as site-specific drug delivery systems. Here, ultrasonic-assisted emulsion copolymerization of N-isopropylacrylamide (NIPAM) and 2-(N,N-diethylaminoethyl) methacrylate (DEAEMA) in the presence of Fe3O4 nanoparticles was employed to prepare pH- and temperature-responsive magnetite nanocomposite particles (MNCPs). The obtained MNCPs were fully characterized by TEM, DSC, FT-IR, VSM, and XRD techniques. They had an average particle size of 70 nm with a lower critical solution temperature of 42 °C and superparamagnetic properties. In addition, MNCPs were loaded with methotrexate (MTX) as an anticancer drug, and their in vitro drug release was studied in different pH values and temperatures and in the presence of an alternating magnetic field. Noteworthy that the highest rate of MTX release was observed at pH 5.5 and 42 °C. Cell viability of the treated MCF-7 human breast cancer cell line with free MTX, MNCPs, and MTX-loaded MNCPs or in combination with magnetic hyperthermia (MHT) and water-based hyperthermia was comparatively studied. The obtained results showed about 17% higher antiproliferative activity for the MTX-loaded MNCPs accompanied by MHT relative to that of free MTX.

Repetitive drug releases from light-activatable micron-sized liposomes.

In this work, a novel light activatable micron-sized liposomal drug carrier that has a unique capability to release drug repetitively in proportion to the cycle number of short irradiation (5 s) of near-infrared (NIR) pulsed laser is reported. We synthesized methotrexate (MTX)-loaded liposomes based on a modified reverse-phase evaporation method. Gold nanorods (AuNR) were attached to the liposomal surfaces, enabling the liposomes to release drug under short NIR irradiation via the photothermal effect. The concentrations of methotrexate (MTX) released from the liposomes were 10.6, 29.8, 43.7 and 65.9 µg/mL after one, two, three or four NIR laser cycles (1.1 W at 1064 nm, 5 s per cycle), respectively. The current finding will provide possible solution to the previously reported inconsistency in drug release from light activatable liposomal drug carriers at each activation cycle. The repeatability of drug release described in this work is believed to be due to reversible nature of the liposomes. The liposomes release drug via lipid bilayer melting when irradiated by laser due to gold nanorods' plasmonic heat on the lipid bilayer surface and quickly regain their original structure once the laser source is removed. We provided evidence of the reversible liposomal structures by monitoring the change of number densities of liposomes using a microelectrode sensor with different laser irradiation durations and powers. We also assessed the micron-sized liposome with respect to long-term stability, drug encapsulation efficiency, and drug-releasing efficiency, demonstrating the possibility of utilizing these liposomes as long-term drug delivery vehicles for various drugs.

Controlled Delivery of Pan-PAD-Inhibitor Cl-Amidine Using Poly(3-Hydroxybutyrate) Microspheres.

This study deals with the process of optimization and synthesis of Poly(3-hydroxybutyrate) microspheres with encapsulated Cl-amidine. Cl-amidine is an inhibitor of peptidylarginine deiminases (PADs), a group of calcium-dependent enzymes, which play critical roles in a number of pathologies, including autoimmune and neurodegenerative diseases, as well as cancer. While Cl-amidine application has been assessed in a number of in vitro and in vivo models; methods of controlled release delivery remain to be investigated. P(3HB) microspheres have proven to be an effective delivery system for several compounds applied in antimicrobial, wound healing, cancer, and cardiovascular and regenerative disease models. In the current study, P(3HB) microspheres with encapsulated Cl-amidine were produced in a size ranging from ~4-5 µm and characterized for surface morphology, porosity, hydrophobicity and protein adsorption, in comparison with empty P(3HB) microspheres. Cl-amidine encapsulation in P(3HB) microspheres was optimized, and these were found to be less hydrophobic, compared with the empty microspheres, and subsequently adsorbed a lower amount of protein on their surface. The release kinetics of Cl-amidine from the microspheres were assessed in vitro and expressed as a function of encapsulation efficiency. There was a burst release of ~50% Cl-amidine in the first 24 h and a zero order release from that point up to 16 days, at which time point ~93% of the drug had been released. As Cl-amidine has been associated with anti-cancer effects, the Cl-amidine encapsulated microspheres were assessed for the inhibition of vascular endothelial growth factor (VEGF) expression in the mammalian breast cancer cell line SK-BR-3, including in the presence of the anti-proliferative drug rapamycin. The cytotoxicity of the combinatorial effect of rapamycin with Cl-amidine encapsulated P(3HB) microspheres was found to be 3.5% more effective within a 24 h period. The cells treated with Cl-amidine encapsulated microspheres alone, were found to have 36.5% reduction in VEGF expression when compared with untreated SK-BR-3 cells. This indicates that controlled release of Cl-amidine from P(3HB) microspheres may be effective in anti-cancer treatment, including in synergy with chemotherapeutic agents. Using controlled drug-delivery of Cl-amidine encapsulated in Poly(3-hydroxybutyrate) microspheres may be a promising novel strategy for application in PAD-associated pathologies.