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Design, produce and assess the viability of a novel nanotechnological antibacterial thermo-sensible intracanal medicament This involves encapsulating calcium hydroxide (Ca(OH)2 ) within polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) and dispersing them in a thermosensitive gel (Ca(OH)2 -NPs-gel). In addition, perform in vitro and ex vivo assessments to evaluate tissue irritation and penetration capacity into dentinal tubules in comparison to free Ca(OH)2 .

The aim of current study is the development and optimization of biodegradable polymeric nanoparticles (NPs) to be used in the field of Endodontics as intracanal medication in cases of avulsed teeth with extended extra-oral time, utilizing PLGA polymers loaded with the anti-inflammatory drug clobetasol propionate (CP).

To date there is no cure for Parkinson’s disease (PD), a devastating neurodegenerative disorder with levodopa being the cornerstone of its treatment. In early PD, levodopa provides a smooth clinical response, but after long-term therapy many patients develop motor complications. Tolcapone (TC) is an effective adjunct in the treatment of PD but has a short elimination half-life. In our work, two new controlled delivery systems of TC consisting of biodegradable PLGA 502 (poly (D,L-lactide-co-glycolide acid) microparticles (MPs) and nanoparticles (NPs) were developed and characterized. Formulations MP-TC4 and NP-TC3 were selected for animal testing. Formulation MP-TC4, prepared with 120 mg TC and 400 mg PLGA 502, exhibited a mean encapsulation efficiency (EE) of 85.13%, and zero-order in vitro release of TC for 30 days, with around 95% of the drug released at this time. Formulation NP-TC3, prepared with 10 mg of TC and 50 mg of PLGA 502, exhibited mean EE of 56.69%, particle size of 182 nm, and controlled the release of TC for 8 days. Daily i.p. (intraperitoneal) doses of rotenone (RT, 2 mg/kg) were given to Wistar rats to induce neurodegeneration. Once established, animals received TC in saline (3 mg/kg/day) or encapsulated within formulations MP-TC4 (amount of MPs equivalent to 3 mg/kg/day TC every 14 days) and NP-TC3 (amount of NPs equivalent to 3 mg/kg/day TC every 3 days). Brain analyses of Nissl-staining, GFAP (glial fibrillary acidic protein), and TH (tyrosine hydroxylase) immunohistochemistry as well as behavioral testing (catalepsy, akinesia, swim test) showed that the best formulation was NP-TC3, which was able to revert PD-like symptoms of neurodegeneration in the animal model assayed, Complutense University of Madrid(UCM) research group "Formulation and Bioavailability of New Drugs", Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, Instituto Universitario de Farmacia Industrial, TRUE, pub

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, with its in cidence constantly increasing. To date, there is no cure for the disease, with a need for new and effective treatments. Morin hydrate (MH) is a naturally occurring flavonoid of the Moraceae family with antioxidant and anti-inflammatory properties; however, the blood–brain barrier (BBB) prevents this flavonoid from reaching the CNS when aiming to potentially treat AD. Seeking to use the LAT-1 transporter present in the BBB, a nanoparticle (NPs) formulation loaded with MH and functional ized with phenylalanine-phenylalanine dipeptide was developed (NPphe-MH) and compared to non-functionalized NPs (NP-MH). In addition, two formulations were prepared using rhodamine B (Rh-B) as a fluorescent dye (NPphe-Rh and NP-Rh) to study their biodistribution and ability to cross the BBB. Functionalization of PLGA NPs resulted in high encapsulation efficiencies for both MH and Rh-B. Studies conducted in Wistar rats showed that the presence of phenylalanine dipeptide in the NPs modified their biodistribution profiles, making them more attractive for both liver and lungs, whereas non-functionalized NPs were predominantly distributed to the spleen. Formulation NPphe-Rh remained in the brain for at least 2 h after administration., Complutense University of Madrid research group. “Formulation and Bioavailability of New Drugs”, Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, Instituto Universitario de Farmacia Industrial, TRUE, pub

The aim of this work was to evaluate the antineoplastic effect of newly synthesized nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) alone or PLGA esterified with 2,2′- [propane-2,2-diylbis (thio)] diacetic acid (TKL), loaded with docetaxel (DTX) and/or docosahexaenoic acid (DHA), as innovative site-specific therapeutic carriers. The obtained materials were characterized by FT-IR and 1H-NMR, while the dimensional analysis of the nanoparticles obtained was performed by Dynamic Light Scattering. The encapsulation efficiency of the nanoparticles was evaluated, and in vitro skin permeation tests were also performed. The antitumor activity of the nanomaterial was studied in the human adenocarcinoma HCT116 cell line. In particular, viability tests in bidimensional culture, as well as in tumor spheroids, were conducted. The use of these nanocarriers could facilitate the stable and efficient delivery of DTX and DHA through the upper segments of the gastrointestinal tract to the colon. In addition, the presence of the ROS-sensitive 2,2′-[propane-2,2-diylbis (thio)] diacetic acid in their matrix should promote the site-specific release of DTX in the tumor mass, where high levels of reactive oxygen species could be found.

Single dose slow-release vaccines herald a new era in vaccine administration. An ideal device for slow-release vaccine delivery would be minimally invasive and self-administered, making these approaches an attractive alternative for mass vaccination programs, particularly during the time of a pandemic. In this review article, we discuss the latest advances in this field, specifically for prophylactic vaccines able to prevent infectious diseases. Recent studies have found that slow-release vaccines elicit better immune responses and often do not require cold chain transportation and storage, thus drastically reducing the cost, streamlining distribution, and improving efficacy. This promise has attracted significant attention, especially when poor patient compliance of the standard multidose vaccine regimes is considered. Single dose slow-release vaccines are the next generation of vaccine tools that could overcome most of the shortcomings of present vaccination programs and be the next platform technology to combat future pandemics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Pathologies affecting the posterior segment are one of the major causes of blindness in developed countries and are becoming more prevalent due to the increase in society longevity. Sucessful therapy of diseases affecting the back of the eye requires effective concentrations of the active substance mantained during a long period of time in the intraocular target site. Treatment of vitreoretinal diseases often include repeated intravitreous injections that are associated with adverse effects. Local administration of biodegradable microspheres offers an excellent alternative to multiple administrations, as they are able to deliver the therapeutic molecule in a controlled fashion. Furthermore, injection of microparticles is performed without the need for surgical procedures. As most of the retinal diseases are multifactorial, microspheres result especially promising because they can be loaded with more than one active substance and complemented with the inclusion of additives with pharmacological properties. Personalized therapy can be easily achieved by changing the amount of administered microspheres. Contrary to non-biodegradable devices, biodegradable PLA and PLGA microspheres disappear from the site of administration after delivering the drug. Furthermore, microspheres prepared from these mentioned biomaterials are well tolerated after periocular and intravitreal injections in animals and humans. After injection, PLA and PLGA microspheres suffer aggregation behaving like an implant. Biodegradable microspheres are potential tools in regenerative medicine for retinal repair. According to the reported results, presumably a variety of microparticulate formulations for different ophthalmic therapeutic uses will be available in the clinical practice in the near future., Unión Europea. FP7, Ministerio de Economía y Competitividad (MINECO), Universidad Complutense de Madrid, Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, pub

The formulation of nanoemulsions by low-energy strategies, particularly by the phase inversion composition method, and the use of these nanoemulsions as templates for the preparation of polymer nanoparticles for biomedical applications are reviewed. The methods of preparation, nature of the components in the formulation, and their impact on the physicochemical properties, drug loading, and drug release are discussed. We highlight the utilization of ethyl cellulose, poly(lactic-co-glycolic acid), and polyurethane/polyurea in the field of nanomedicine as potential drug delivery systems. Advances are still needed to achieve better control over size distribution, nanoparticle concentration, surface functionalization, and the type of polymers that can be processed

Dementia affects around 50 million people worldwide and it is one of the main causes of disability and dependency. The incidence of dementia is projected to increase rapidly over the next several decades. However, despite these increased number of people suffering from this syndrome, available pharmacological treatments are highly limited. Nanotechnological approaches could constitute the key to deliver drugs effectively to the target site in a prolonged manner and avoiding undesired adverse effects. Polymeric nanoparticles are one of the most promising drug delivery systems, being able to encapsulate a wide variety of compounds. Several studies had been made using nanoparticles, especially for Alzheimer’s disease. This chapter analyses the different types of dementia and provides a critical and global vision of the main polymers used to develop polymeric nanoparticles and their specific applications for dementia. An overview about functionalization strategies employed for the treatment of dementia is also carried out.

Researchers have explored natural products to combat the antibiotic resistance of various microorganisms. Cinnamaldehyde (CIN), a major component of cinnamon essential oil (CC-EO), has been found to effectively inhibit the growth of bacteria, fungi, and mildew, as well as their production of toxins. Therefore, this study aimed to create a delivery system for CIN using PLGA microparticles (CIN-MPs), and to compare the antifungal activity of the carried and free CIN, particularly against antibiotic-resistant strains of Candida spp. The first part of the study focused on synthesizing and characterizing the PLGA MPs, which had no toxic effects in vivo and produced results in line with the existing literature. The subsequent experiments analyzed the antifungal effects of MPs-CIN on Candida albicans and Candida glabrata, both resistant (R) and sensitive (S) strains and compared its efficacy with the conventional addition of free CIN to the culture medium. The results indicated that conveyed CIN increased the antifungal effects of the product, particularly towards C. albicans R. The slow and prolonged release of CIN from the PLGA MPs ensured a constant and uniform concentration of the active principle within the cells.

Therapeutics are habitually characterized by short plasma half-lives and little affinity for targeted cells. To overcome these challenges, nanoparticulate systems have entered into the disease arena. Poly(d,l-lactide-co-glycolide) (PLGA) is one of the most relevant biocompatible materials to construct drug nanocarriers. Understanding the physical chemistry of this copolymer and current knowledge of its biological fate will help in engineering efficient PLGA-based nanomedicines. Surface modification of the nanoparticle structure has been proposed as a required functionalization to optimize the performance in biological systems and to localize the PLGA colloid into the site of action. In this review, a background is provided on the properties and biodegradation of the copolymer. Methods to formulate PLGA nanoparticles, as well as their in vitro performance and in vivo fate, are briefly discussed. In addition, a special focus is placed on the analysis of current research in the use of surface modification strategies to engineer PLGA nanoparticles, i.e., PEGylation and the use of PEG alternatives, surfactants and lipids to improve in vitro and in vivo stability and to create hydrophilic shells or stealth protection for the nanoparticle. Finally, an update on the use of ligands to decorate the surface of PLGA nanomedicines is included in the review.

Therapeutics are habitually characterized by short plasma half-lives and little affinity for targeted cells. To overcome these challenges, nanoparticulate systems have entered into the disease arena. Poly(d,l-lactide-co-glycolide) (PLGA) is one of the most relevant biocompatible materials to construct drug nanocarriers. Understanding the physical chemistry of this copolymer and current knowledge of its biological fate will help in engineering efficient PLGA-based nanomedicines. Surface modification of the nanoparticle structure has been proposed as a required functionalization to optimize the performance in biological systems and to localize the PLGA colloid into the site of action. In this review, a background is provided on the properties and biodegradation of the copolymer. Methods to formulate PLGA nanoparticles, as well as their in vitro performance and in vivo fate, are briefly discussed. In addition, a special focus is placed on the analysis of current research in the use of surface modification strategies to engineer PLGA nanoparticles, i.e., PEGylation and the use of PEG alternatives, surfactants and lipids to improve in vitro and in vivo stability and to create hydrophilic shells or stealth protection for the nanoparticle. Finally, an update on the use of ligands to decorate the surface of PLGA nanomedicines is included in the review.

Therapeutics are habitually characterized by short plasma half-lives and little affinity for targeted cells. To overcome these challenges, nanoparticulate systems have entered into the disease arena. Poly(d,l-lactide-co-glycolide) (PLGA) is one of the most relevant biocompatible materials to construct drug nanocarriers. Understanding the physical chemistry of this copolymer and current knowledge of its biological fate will help in engineering efficient PLGA-based nanomedicines. Surface modification of the nanoparticle structure has been proposed as a required functionalization to optimize the performance in biological systems and to localize the PLGA colloid into the site of action. In this review, a background is provided on the properties and biodegradation of the copolymer. Methods to formulate PLGA nanoparticles, as well as their in vitro performance and in vivo fate, are briefly discussed. In addition, a special focus is placed on the analysis of current research in the use of surface modification strategies to engineer PLGA nanoparticles, i.e., PEGylation and the use of PEG alternatives, surfactants and lipids to improve in vitro and in vivo stability and to create hydrophilic shells or stealth protection for the nanoparticle. Finally, an update on the use of ligands to decorate the surface of PLGA nanomedicines is included in the review.

Rapid joint clearance of small molecule drugs is the major limitation of current clinical approaches to osteoarthritis and its subtypes, including post-traumatic osteoarthritis (PTOA). Particulate systems such as nano/microtechnology could provide a potential avenue for improved joint retention of small molecule drugs. One drug of interest for PTOA treatment is flavopiridol, which inhibits cyclin-dependent kinase 9 (CDK9). Herein, polylactide-co-glycolide microparticles encapsulating flavopiridol were formulated, characterized, and evaluated as a strategy to mitigate PTOA-associated inflammation through the inhibition of CDK9. Characterization of the microparticles, including the drug loading, hydrodynamic diameter, stability, and release profile was performed. The mean hydrodynamic diameter of flavopiridol particles was ∼15 µm, indicating good syringeability and low potential for phagocytosis. The microparticles showed no cytotoxicity in-vitro, and drug activity was maintained after encapsulation, even after prolonged exposure to high temperatures (60 °C). Flavopiridol-loaded microparticles or blank (unloaded) microparticles were administered by intraarticular injection in a rat knee injury model of PTOA. We observed significant joint retention of flavopiridol microparticles compared to the soluble flavopiridol, confirming the sustained release behavior of the particles. Matrix metalloprotease (MMP) activity, an indicator of joint inflammation, was significantly reduced by flavopiridol microparticles 3 days post-injury. Histopathological analysis showed that flavopiridol microparticles reduced PTOA severity 28 days post-injury. Taken altogether, this work demonstrates a promising biomaterial platform for sustained small molecule drug delivery to the joint space as a therapeutic measure for post-traumatic osteoarthritis. STATEMENT OF SIGNIFICANCE: Post-traumatic osteoarthritis (PTOA) begins with the deterioration of subchondral bone and cartilage after acute injurie

Therapeutics are habitually characterized by short plasma half-lives and little affinity for targeted cells. To overcome these challenges, nanoparticulate systems have entered into the disease arena. Poly(d,l-lactide-co-glycolide) (PLGA) is one of the most relevant biocompatible materials to construct drug nanocarriers. Understanding the physical chemistry of this copolymer and current knowledge of its biological fate will help in engineering efficient PLGA-based nanomedicines. Surface modification of the nanoparticle structure has been proposed as a required functionalization to optimize the performance in biological systems and to localize the PLGA colloid into the site of action. In this review, a background is provided on the properties and biodegradation of the copolymer. Methods to formulate PLGA nanoparticles, as well as their in vitro performance and in vivo fate, are briefly discussed. In addition, a special focus is placed on the analysis of current research in the use of surface modification strategies to engineer PLGA nanoparticles, i.e., PEGylation and the use of PEG alternatives, surfactants and lipids to improve in vitro and in vivo stability and to create hydrophilic shells or stealth protection for the nanoparticle. Finally, an update on the use of ligands to decorate the surface of PLGA nanomedicines is included in the review.

Therapeutics are habitually characterized by short plasma half-lives and little affinity for targeted cells. To overcome these challenges, nanoparticulate systems have entered into the disease arena. Poly(d,l-lactide-co-glycolide) (PLGA) is one of the most relevant biocompatible materials to construct drug nanocarriers. Understanding the physical chemistry of this copolymer and current knowledge of its biological fate will help in engineering efficient PLGA-based nanomedicines. Surface modification of the nanoparticle structure has been proposed as a required functionalization to optimize the performance in biological systems and to localize the PLGA colloid into the site of action. In this review, a background is provided on the properties and biodegradation of the copolymer. Methods to formulate PLGA nanoparticles, as well as their in vitro performance and in vivo fate, are briefly discussed. In addition, a special focus is placed on the analysis of current research in the use of surface modification strategies to engineer PLGA nanoparticles, i.e., PEGylation and the use of PEG alternatives, surfactants and lipids to improve in vitro and in vivo stability and to create hydrophilic shells or stealth protection for the nanoparticle. Finally, an update on the use of ligands to decorate the surface of PLGA nanomedicines is included in the review.

Therapeutics are habitually characterized by short plasma half-lives and little affinity for targeted cells. To overcome these challenges, nanoparticulate systems have entered into the disease arena. Poly(d,l-lactide-co-glycolide) (PLGA) is one of the most relevant biocompatible materials to construct drug nanocarriers. Understanding the physical chemistry of this copolymer and current knowledge of its biological fate will help in engineering efficient PLGA-based nanomedicines. Surface modification of the nanoparticle structure has been proposed as a required functionalization to optimize the performance in biological systems and to localize the PLGA colloid into the site of action. In this review, a background is provided on the properties and biodegradation of the copolymer. Methods to formulate PLGA nanoparticles, as well as their in vitro performance and in vivo fate, are briefly discussed. In addition, a special focus is placed on the analysis of current research in the use of surface modification strategies to engineer PLGA nanoparticles, i.e., PEGylation and the use of PEG alternatives, surfactants and lipids to improve in vitro and in vivo stability and to create hydrophilic shells or stealth protection for the nanoparticle. Finally, an update on the use of ligands to decorate the surface of PLGA nanomedicines is included in the review.

A facile and robust microfluidic method to produce nanoparticle-in-microparticle systems (Trojan systems) is reported as a delivery vector for the oral administration of active pharmaceutical ingredients. The microfluidic system is based on two coaxial capillaries that produce monodisperse water-in-oil-in-water (W/O/W) double emulsions in a highly controlled fashion with precise control over the resulting particle structure, including the core and shell dimensions. The influence of the three phase flow rates, pH and drying process on the formation and overall size is evaluated. These droplets are then used as templates for the production of pH-sensitive Trojan microparticles after solvent evaporation. The shell of Trojan microparticles is made of Eudragit®, a methacrylic acid-ethyl acrylate copolymer that would enable the Trojan microparticle payload to first pass through the stomach without being degraded and then dissolve in the intestinal fluid, releasing the inner payload. The synthesis of the pH-sensitive Trojan microparticles was also compared with a conventional batch production method. The payloads considered in this work were different in nature: (1) fluorescein, to validate the feasibility of the polymeric shell to protect the payload under gastric pH; (2) poly(D,L-lactic acid/glycolic acid)-PLGA nanoparticles loaded with the antibiotic rifampicin. These PLGA nanoparticles were produced also using a microfluidic continuous process and (3) PLGA nanoparticles loaded with Au nanoparticles to trace the PLGA formulation under different environments (gastric and intestinal), and to assess whether active pharmaceutical ingredient (API) encapsulation in PLGA is due efficiently. We further showed that Trojan microparticles released the embedded PLGA nanoparticles in contact with suitable media, as confirmed by electron microscopy. Finally, the results show the possibility of developing Trojan microparticles in a continuous manner with the ability to deliver therape

Virgin olive oil, the main source of fat in the Mediterranean diet, contains a substantial amount of squalene which possesses natural antioxidant properties. Due to its highly hydrophobic nature, its bioavailability is reduced. In order to increase its delivery and potentiate its actions, squalene has been loaded into PLGA nanoparticles (NPs). The characterization of the resulting nanoparticles was assessed by electron microscopy, dynamic light scattering, zeta potential and high-performance liquid chromatography. Reactive oxygen species (ROS) generation and cell viability assays were carried out in AML12 (alpha mouse liver cell line) and a TXNDC5-deficient AML12 cell line (KO), which was generated by CRISPR/cas9 technology. According to the results, squalene was successfully encapsulated in PLGA NPs, and had rapid and efficient cellular uptake at 30 µM squalene concentration. Squalene reduced ROS in AML12, whereas ROS levels increased in KO cells and improved cell viability in both when subjected to oxidative stress by significant induction of Gpx4. Squalene enhanced cell viability in ER-induced stress by decreasing Ern1 or Eif2ak3 expressions. In conclusion, TXNDC5 shows a crucial role in regulating ER-induced stress through different signaling pathways, and squalene protects mouse hepatocytes from oxidative and endoplasmic reticulum stresses by several molecular mechanisms depending on TXNDC5.

Endodontic-related diseases constitute the fourth most expensive pathologies in industrialized countries. Specifically, endodontics is the part of dentistry focused on treating disorders of the dental pulp and its consequences. In order to treat these problems, especially endodontic infections, dental barriers and complex root canal anatomy should be overcome. This constitutes an unmet medical need since the rate of successful disinfection with the currently marketed drugs is around 85%. Therefore, nanoparticles constitute a suitable alternative in order to deliver active compounds effectively to the target site, increasing their therapeutic efficacy. Therefore, in the present review, an overview of dental anatomy and the barriers that should be overcome for effective disinfection will be summarized. In addition, the versatility of nanoparticles for drug delivery and their specific uses in dentistry are comprehensively discussed. Finally, the latest findings, potential applications and state of the art nanoparticles with special emphasis on biodegradable nanoparticles used for endodontic disinfection are also reviewed.

Rosmarinic acid (RA), a caffeic acid derivative, has been loaded in polymeric nanoparticles made up of poly(lactic-co-glycolic acid) (PLGA) through a nano-emulsion templating process using the phase-inversion composition (PIC) method at room temperature. The obtained RA-loaded nanoparticles (NPs) were colloidally stable exhibiting average diameters in the range of 70-100 nm. RA was entrapped within the PLGA polymeric network with high encapsulation efficiencies and nanoparticles were able to release RA in a rate-controlled manner. A first-order equation model fitted our experimental data and confirmed the prevalence of diffusion mechanisms. Protein corona formation on the surface of NPs was assessed upon incubation with serum proteins. Protein adsorption induced an increase in the hydrodynamic diameter and a slight shift towards more negative surface charges of the NPs. The radical scavenging activity of RA-loaded NPs was also studied using the DPPH·assay and showed a dose-response relationship between the NPs concentration and DPPH inhibition. Finally, RA-loaded NPs did not affect the cellular proliferation of the human neuroblastoma SH-SY5Y cell line and promoted efficient cellular uptake. These results are promising for expanding the use of O/W nano-emulsions in biomedical applications.

Nearly four million yearly deaths can be attributed to respiratory diseases, prompting a huge worldwide health emergency. Additionally, the COVID-19 pandemic’s death toll has surpassed six million, significantly increasing respiratory disease morbidity and mortality rates. Despite recent advances, it is still challenging for many drugs to be homogeneously distributed throughout the lungs, and specifically to reach the lower respiratory tract with an accurate sustained dose and minimal systemic side effects. Engineered nanocarriers can provide increased therapeutic efficacy while lessening potential biochemical adverse reactions. Poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer, has attracted significant interest as an inhalable drug delivery system. However, the influence of the nanocarrier surface charge and its intratracheal instillation has not been addressed so far. In this study, we fabricated red fluorescent PLGA nanocapsules (NCs)—Cy5/PLGA—with either positive (Cy5/PLGA+) or negative surface charge (Cy5/PLGA-). We report here on their excellent colloidal stability in culture and biological media, and after cryo-storage. Their lack of cytotoxicity in two relevant lung cell types, even for concentrations as high as 10 mg/mL, is also reported. More importantly, differences in the NCs’ cell uptake rates and internalization capacity were identified. The uptake of the anionic system was faster and in much higher amounts—10-fold and 2.5-fold in macrophages and epithelial alveolar cells, respectively. The in vivo study demonstrated that anionic PLGA NCs were retained in all lung lobules after 1 h of being intratracheally instilled, and were found to accumulate in lung macrophages after 24 h, making those nanocarriers especially suitable as a pulmonary immunomodulatory delivery system with a marked translational character.

The increasing use of mechanical thrombectomy in stroke management has opened the window to local intraarterial brain delivery of therapeutic agents. In this context, the use of nanomedicine could further improve the delivery of new treatments for specific brain targeting, tracking and guidance. In this study we take advantage of this new endovascular approach to deliver biocompatible poly(D-L-lactic-co-glycolic acid) (PLGA) nanocapsules functionalized with superparamagnetic iron oxide nanoparticles and Cy7.5 for magnetic targeting, magnetic resonance and fluorescent molecular imaging. A complete biodistribution study in naïve (n = 59) and ischemic (n = 51) mice receiving intravenous or intraarterial nanocapsules, with two different magnet devices and imaged from 30 min to 48 h, showed an extraordinary advantage of the intraarterial route for brain delivery with a specific improvement in cortical targeting when using a magnetic device in both control and ischemic conditions. Safety was evaluated in ischemic mice (n = 69) showing no signs of systemic toxicity nor increasing mortality, infarct lesions or hemorrhages. In conclusion, the challenging brain delivery of therapeutic nanomaterials could be efficiently and safely overcome with a controlled endovascular administration and magnetic targeting, which could be considered in the context of endovascular interventions for the delivery of multiple treatments for stroke.

Licochalcone-A is a natural compound with anti-inflammatory properties. However, it possesses low water solubility, making its application for the treatment of ocular inflammation difficult. To overcome this drawback, biodegradable nanoparticles incorporating Licochalcone-A have been developed. Additionally, to avoid fast clearance and increase cellular internalization into the ocular tissues, PLGA nanoparticles have been functionalized using PEG and cell penetrating peptides (Tet-1 and B6). To optimize the formulations, a factorial design was carried out and short-term stability of the nanoparticles was studied. Moreover, morphology was also observed by transmission electron microcopy and in vitro drug release was carried out. Ocular tolerance of the formulations was ensured in vitro and in vivo and anti-inflammatory therapeutic efficacy was also assessed. Surface functionalized nanoparticles loading Licochalcone-A were developed with an average size below 200 nm, a positive surface charge, and a monodisperse population. The formulations were non-irritant and showed a prolonged Licochalcone-A release. Despite the fact that both Licochalcone-A Tet-1 and B6 functionalized nanoparticles demonstrated to be suitable for the treatment of ocular inflammation, B6 targeted nanoparticles provided greater therapeutic efficacy in in vivo assays.

[EN] Poly(lactic-co-glycolic acid) (PLGA) and poly(caprolactone-co-glycolic acid) (PCLGA) solutions were electrospun into membranes with tailored fiber diameter of 1.8 mu m. This particular fiber diameter was tuned depending on the used co-polymer by adjusting the electrospinning parameters that mainly influence the fiber diameter. The greatest setting of the fiber diameter was achieved by varying the polymer solution parameters (polymer concentration, solvents and solvents ratio). PLGA was adequately electrospun with 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), whereas PCLGA required a polar solvent (such as chloroform) with a lower dielectric constant. Moreover, due to the amorphous morphology of PCLGA, pyridine as salt had to be added to the starting solution to increase its conductivity and make it electrospinnable. Indeed, the electrospinning of this co-polymer presents notable difficulties due to its amorphous structure. Interestingly, PCLGA, having a higher glycolic acid molar fraction than commonly electrospun co-polymers (caprolactone:glycolic acid ratio of 45:55 instead of 90:10), could be successfully electrospun, which has not been reported to date. To an accurate setting of fiber diameter, the voltage and the distance from needle to collector were varied. Finally, the study of the surface tension, conductivity and viscosity of the polymer solutions allowed to correlate these particular characteristics of the solutions with the electrospinning variables so that prior knowledge of them enables predicting the required processing conditions.

[EN] Poly(lactic-co-glycolic acid) (PLGA) and poly(caprolactone-co-glycolic acid) (PCLGA) solutions were electrospun into membranes with tailored fiber diameter of 1.8 mu m. This particular fiber diameter was tuned depending on the used co-polymer by adjusting the electrospinning parameters that mainly influence the fiber diameter. The greatest setting of the fiber diameter was achieved by varying the polymer solution parameters (polymer concentration, solvents and solvents ratio). PLGA was adequately electrospun with 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), whereas PCLGA required a polar solvent (such as chloroform) with a lower dielectric constant. Moreover, due to the amorphous morphology of PCLGA, pyridine as salt had to be added to the starting solution to increase its conductivity and make it electrospinnable. Indeed, the electrospinning of this co-polymer presents notable difficulties due to its amorphous structure. Interestingly, PCLGA, having a higher glycolic acid molar fraction than commonly electrospun co-polymers (caprolactone:glycolic acid ratio of 45:55 instead of 90:10), could be successfully electrospun, which has not been reported to date. To an accurate setting of fiber diameter, the voltage and the distance from needle to collector were varied. Finally, the study of the surface tension, conductivity and viscosity of the polymer solutions allowed to correlate these particular characteristics of the solutions with the electrospinning variables so that prior knowledge of them enables predicting the required processing conditions.

peer-reviewed, The full text of this article will not be available in ULIR until the embargo expires on the 09/01/02021, The blood-brain barrier (BBB) has a significant contribution to homeostasis and protection of the CNS. However, it also limits the crossing of therapeutics and thereby complicates the treatment of CNS disorders. To overcome this limitation, the use of nanocarriers for drug delivery across the BBB has recently been exploited. Nanocarriers can utilize different physiological mechanisms for drug delivery across the BBB and can be modified to achieve the desired kinetics and efficacy. Consequentially, several nanocarriers have been reported to act as functional nanomedicines in preclinical studies using animal models for human diseases. Given the rapid development of novel nanocarriers, this review provides a comprehensive insight into the most recent advancements made in nanocarrier-based drug delivery to the CNS, such as the development of multifunctional nanomedicines and theranostics., peer-reviewed

Several attempts have been made to encapsulate indomethacin (IND), to control its sustained release and reduce its side effects. To develop a successful formulation, drug release from a polymeric matrix and subsequent biodegradation need to be achieved. In this study, we focus on combining microfluidic and artificial intelligence (AI) technologies, alongside using biomaterials, to generate drug-loaded polymeric microparticles (MPs). Our strategy is based on using Poly (D,L-lactide-co-glycolide) (PLGA) as a biodegradable polymer for the generation of a controlled drug delivery vehicle, with IND as an example of a poorly soluble drug, a 3D flow focusing microfluidic chip as a simple device synthesis particle, and machine learning using artificial neural networks (ANNs) as an in silico tool to generate and predict size-tunable PLGA MPs. The influence of different polymer concentrations and the flow rates of dispersed and continuous phases on PLGA droplet size prediction in a microfluidic platform were assessed. Subsequently, the developed ANN model was utilized as a quick guide to generate PLGA MPs at a desired size. After conditions optimization, IND-loaded PLGA MPs were produced, and showed larger droplet sizes than blank MPs. Further, the proposed microfluidic system is capable of producing monodisperse particles with a well-controllable shape and size. IND-loaded-PLGA MPs exhibited acceptable drug loading and encapsulation efficiency (7.79 and 62.35%, respectively) and showed sustained release, reaching approximately 80% within 9 days. Hence, combining modern technologies of machine learning and microfluidics with biomaterials can be applied to many pharmaceutical applications, as a quick, low cost, and reproducible strategy., QC 20211028

Purpose: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment. Methods: By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation. Results: With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9 +/- 1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96 +/- 1.88)% compared with (0.99 +/- 0.10)% in PBS group, revealing the enhanced immune response against PCa. Conclusion: The dual-functional P

A critical component of tissue engineering is the ability to functionally replace native tissue stroma. Electrospinning is a technique capable of forming fibrous constructs with a high surface area for increased cell-material interaction and enhanced biocompatibility. However, physical and biological properties of electrospun scaffolds are limited by design controllability on a macroscale. We developed a methodology for generating electrospun scaffolds with defined patterns and topographic features to influence physical properties and biological interactions. Five unique design electrospinning target collectors were fabricated to allow for generation of defined polymeric scaffold patterns including lines, sinusoids, squares, zigzags, and solid. Poly(lactic-co-glycolic) acid was electrospun under identical conditions utilizing these varied targets, and constructs generated were examined as to their physical configuration, mechanical and chemical properties, and their ability to foster vascular smooth muscle cell adhesion and retention at 24 h. Modifying collector designs led to significant differences in fiber target coverage ranging from 300 mm2 for solid (100% of the target area) to 217.8 mm2 for lines (72.6% of the target area). Measured fiber excess, residual open area, and contact angle (hydrophobicity) followed the same trend as fiber target coverage with respect to the collector pattern: lines > sinusoids > squares > zigzags > solid. Similarly, the line design allowed for the greatest cell adhesion and retention (258 ± 31 cells), whereas solid exhibited the lowest (150 ± 15 cells); p < 0.05. There was a strong direct correlation of cell adhesion to construct residual open area (R2 = 0.94), normalized fiber excess (R2 = 0.99), and fiber grammage (R2 = 0.72), with an inverse relationship to fiber target coverage (R2 = 0.94). Our results demonstrate the ability to utilize patterned collectors for modifying macroscopic and microscopic electrospun sc

The effect of fiber diameter size on the controlled release of small molecule model drugs from dual electrospun polymeric nanofiber mats was investigated by fabricating poly(lactide-co-glycolide) (PLGA) electrospun nanofibers from polymeric solutions that incorporated rhodamine B (RhB) and Rhodamine 800 (Rh800) as model drugs. Different ratios of dimethylformamide (DMF) and Dichloromethane (DCM) in the electrospinning polymeric solution were used to produce varying diameters of the PLGA nanofibers, and drug diffusion was tested in vitro. PLGA shrinks under in vitro conditioning due to the plasticizing effects of water, so samples were annealed before testing. The resulting dual electrospun fiber mat consisted of ~250 nm PLGA fibers with Rh800 and ~450 nm PLGA fibers with RhB. The drug release profiles of rhodamine B from the dual electrospun PLGA fiber mat indicated a two phase burst release separated by a lag phase. The drug release profile of Rh800 from the dual electrospun PLGA fiber mat showed a lag phase over the first week and then a burst phase at a relatively higher rate than of the second burst phase of RhB. The first burst phase of RhB was attributed to the relatively solubility of RhB in DMF compared to DCM, where RhB is less solubility in DMF and thus was not uniformly distributed throughout the nanofibers. The second burst phase and lag phase was attributed to the autocatalyzed bulk degradation of PLGA.

The development of new gene-editing technologies has fostered the need for efficient and safe vectors capable of encapsulating large nucleic acids. In this work we evaluate the synthesis of large-size plasmid-loaded PLGA nanoparticles by double emulsion (considering batch ultrasound and microfluidics-assisted methodologies) and magnetic stirring-based nanoprecipitation synthesis methods. For this purpose, we characterized the nanoparticles and compared the results between the different synthesis processes in terms of encapsulation efficiency, morphology, particle size, polydispersity, zeta potential and structural integrity of loaded pDNA. Our results demonstrate particular sensibility of large pDNA for shear and mechanical stress degradation during double emulsion, the nanoprecipitation method being the only one that preserved plasmid integrity. However, plasmid-loaded PLGA nanoparticles synthesized by nanoprecipitation did not show cell expression in vitro, possibly due to the slow release profile observed in our experimental conditions. Strong electrostatic interactions between the large plasmid and the cationic PLGA used for this synthesis may underlie this release kinetics. Overall, none of the methods evaluated satisfied all the requirements for an efficient non-viral vector when applied to large-size plasmid encapsulation. Further optimization or alternative synthesis methods are thus in current need to adapt PLGA nanoparticles as delivery vectors for gene editing therapeutic technologies.

Cell-penetrating peptides (CPPs) are known to interact with cell membranes and by doing so enhance cellular interaction and subsequent cellular internalization of nanoparticles. Yet, the early events of membrane interactions are still not elucidated, which is the aim of the present work. Surface conjugation of polymeric nanoparticles with cationic CPPs of different architecture (short, long linear, and branched) influences the surface properties, especially the charge of the nanoparticles, and therefore provides the possibility of increased electrostatic interactions between nanoparticles with the cell membrane. In this study, the physicochemical properties of CPP-tagged poly(lactic-co-glycolic acid) (PLGA) nanoparticles were characterized, and nanoparticle-cell interactions were investigated in HeLa cells. With the commonly applied methods of flow cytometry as well as confocal laser scanning microscopy, low and similar levels of nanoparticle association were detected for the PLGA and CPP-tagged PLGA nanoparticles with the cell membrane. However, single particle tracking of CPP-tagged PLGA nanoparticles allowed direct observation of the interactions of individual nanoparticles with cells and consequently elucidated the impact that the CPP architecture on the nanoparticle surface can have. Interestingly, the results revealed that nanoparticles with the branched CPP architecture on the surface displayed decreased diffusion modes likely due to increased interactions with the cell membrane when compared to the other nanoparticles investigated. It is anticipated that single particle approaches like the one used here can be widely employed to reveal currently unresolved characteristics of nanoparticle-cell interaction and aid in the design of improved surface-modified nanoparticles for efficient delivery of therapeutics.

Therapies targeting neurological conditions such as Alzheimer's or Parkinson's diseases are hampered by the presence of the blood-brain barrier (BBB). During the last decades, several approaches have been developed to overcome the BBB, such as the use of nanoparticles (NPs) based on biomaterials, or alternative methods to open the BBB. In this review, we briefly highlight these strategies and the most recent advances in this field. Limitations and advantages of each approach are discussed. Combination of several methods such as functionalized NPs targeting the receptor-mediated transcytosis system with the use of magnetic resonance imaging-guided focused ultrasound (FUS) might be a promising strategy to develop theranostic tools as well as to safely deliver therapeutic molecules, such as drugs, neurotrophic factors or antibodies within the brain parenchyma.

Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7’s role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-(1H)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor.

A potent cell division cycle 7 (CDC7) kinase inhibitor, known as PHA-767491, has been described to reduce the transactive response DNA binding protein of 43 KDa (TDP-43) phosphorylation in vitro and in vivo, which is one of the main proteins found to aggregate and accumulate in the cytoplasm of motoneurons in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. However, the main drawback of this compound is its low permeability to the central nervous system (CNS), limiting its use for the treatment of neurological conditions. In this context, the use of drug delivery systems like nanocarriers has become an interesting approach to improve drug release to the CNS. In this study, we prepared and characterized biodegradable nanoparticles in order to encapsulate PHA-767491 and improve its permeability to the CNS. Our results demonstrate that poly (lactic-co-glycolic acid) (PLGA) nanoparticles with an average radius between 145 and 155 nm could be used to entrap PHA-767491 and enhance the permeability of this compound through the blood–brain barrier (BBB), becoming a promising candidate for the treatment of TDP-43 proteinopathies such as ALS.

Thèse réalisée dans le cadre d'une collaboration avec UCB Pharma et la région Wallonne s'inscrivant dans le cadre du projet SAS. Le but de ce projet était de développer des implants sous-cutanés imprimés en trois dimensions pour permettre une libération d’anticorps thérapeutique de manière prolongée au cours du temps. En effet, les thérapies disponibles sont souvent administrées par voie intraveineuse, ce qui peut réduire la compliance des patients dû à l’inconfort et à la fréquence de ces administrations. Les systèmes de délivrance, tels que des implants, peuvent limiter les fréquences d’administration grâce à l’insertion d’un dispositif qui libèrera le principe actif au cours du temps durant une période donnée. Les implants s’inscrivent comme une alternative aux microsphères qui sont également des dispositifs développés et investigués en vue de favoriser l’adhésion et la compliance des patients. L’avènement du 3D dans le milieu pharmaceutique a montré une certaine frénésie liée au développement de la médecine personnalisée et à l’innovation du procédé dans ce secteur. La sélection d’un matériau biocompatible et biorésorbable tel que le PLGA représente une véritable plus-value dans le développement d’implant. Etant donné que ces implants sont biodégradables, le retrait n’est pas à envisager, ce qui limite les désagréments du patient à un seul acte chirurgical lors de l’implantation. Au cours de ce travail, une approche pragmatique a d’abord été abordée sur les procédés d’extrusion à chaud et de l’impression 3D en utilisant un polymère couramment employé dans l’impression grand public, le PLA. L’investigation des paramètres d’impressions (température d’impression, epaisseur de couche et vitesse d’impression) et l’usage de divers plastifiants (la triacétine (TA), le polyethylène glycol 400 (PEG 400), le citrate de triéthyle (TEC) et l’acétyle citrate de triéthyle (ATEC)) pour faciliter les procédés à chaud et dans l’idée de réduire les températures d’extrusion et d’i, Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie), info:eu-repo/semantics/nonPublished

The increasing use of mechanical thrombectomy in stroke management has opened the window to local intraarterial brain delivery of therapeutic agents. In this context, the use of nanomedicine could further improve the delivery of new treatments for specific brain targeting, tracking and guidance. In this study we take advantage of this new endovascular approach to deliver biocompatible poly(D-L-lactic-co-glycolic acid) (PLGA) nanocapsules functionalized with superparamagnetic iron oxide nanoparticles and Cy7.5 for magnetic targeting, magnetic resonance and fluorescent molecular imaging. A complete biodistribution study in naïve (n = 59) and ischemic (n = 51) mice receiving intravenous or intraarterial nanocapsules, with two different magnet devices and imaged from 30 min to 48 h, showed an extraordinary advantage of the intraarterial route for brain delivery with a specific improvement in cortical targeting when using a magnetic device in both control and ischemic conditions. Safety was evaluated in ischemic mice (n = 69) showing no signs of systemic toxicity nor increasing mortality, infarct lesions or hemorrhages. In conclusion, the challenging brain delivery of therapeutic nanomaterials could be efficiently and safely overcome with a controlled endovascular administration and magnetic targeting, which could be considered in the context of endovascular interventions for the delivery of multiple treatments for stroke.

Despite several shortcomings such as extreme hydrophobicity, low drug capacity, characteristic triphasic drug release pattern with a high burst effect, poly(lactic-co-glycolic acid derivatives are widely used in drug delivery. Most frequent attempts to improve their properties are blending with other polymers or synthesis of block copolymers. We introduce a new class of branched poly(lactic-co-glycolic acid) derivatives as promising biodegradable carriers for prolonged or targeted drug release systems, employed as thin adhesive films, solid dispersions, in situ forming implants or nanoparticles. A series of poly(lactic-co-glycolic acid) derivatives with lower molar mass and star or comb architecture were synthesized by a simple, catalyst free, direct melt polycondensation method not requiring purification of the obtained sterile product by precipitation. Branching monomers used were mannitol, pentaerythritol, dipentaerythritol, tripentaerythritol and polyacrylic acid. The products were characterized by molar mass averages, average branching ratio, rheological and thermal properties., Přes některé nedostatky, deriváty kyseliny poly(mléčné-co-glykolové) jsou široce používány jako drug-delivery materiály. Práce představuje nový typ větvené kyseliny poly(mléčné-co-glykolové) jako slibného biodegradabilního materiálu. Série větvené kyseliny poly(mléčné-co-glykolové) byla připravena přímou kondenzací v tavenině bez použití katalyzátoru. Získané produkty nevyžadovaly čištění srážením. Jako větvící monomery byly použity mannitol, pentaerythritol, dipentaerythritol, tripentaerythritol and kyselina polyakrylová. Produkty byly charakterizovány molární hmotností, průměrným větvícím poměrem a rheologickými a termálními vlastnostmi.

To facilitate the administration of combined 5-Fluorouracil (5-FU) and gold nanoparticles (for photothermal treatment purposes), we developed 5-FU-gold-poly(lactide-co-glycolic acid) (5-FU-Au- PLGA) nanovehicles, via the nanoprecipitation method. The gold nanoparticles were incorporated inside the 5-FU-PLGA carriers using a roller mixer. Morphological analysis using atomic force microscopy (AFM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), indicated uniform, singly separated spherical nanoparticles (NPs). Drug content, recovery and entrapment in the NPs were approximated using UV-spectrophotometer data. Approximately 26% of nanoparticles were recovered after drying. The percentage of total drug content was about 30%, and the percentage of drug entrapment reached 57%. Electrostatic Force Microscopy images confirmed the presence of gold inside the drug-loaded nanoparticles. We speculate that the 20-nm gold particles were able to diffuse, after 12 hours of mixing (using the roller mixer), into the PLGA matrix through the 100-nm pores (observed by SEM) without affecting the integrity of the drug delivery vehicle. These synthesized nanoparticles show promise as multimodal vehicles in the delivery of chemotherapeutic agents.

[ES] En el presente trabajo la alumna realizará síntesis de nanoparticulas polimericas (PLGA-Alginato y Fe-CS) mediante una técnica de nanoprecipitación con la finalidad de obtener partículas nanométricas y se obtendrá una caracterización a fondo de estas mismas. Tras esto se analizará la encapsulación de un colorante para realizar un estudio sobre cuan factible es esta técnica para la inicial hipotesis de encapsular un farmaco de caracteristicas similares al colorante. Y por ultimo, se encapsulará el fármaco y se hará un estudio de degradación y de liberación del fármaco en cuestión., [EN] Since the present, trend points to an increasing interest in the use of natural ingredients in food, drugs, and cosmetics(Tønnesen & Karlsen, 2002).Therefore, the use of biodegradable polymers, in the aforementioned applications have pushed research into working with them. Natural polymers, biopolymers, have advantages such as they are non-allergic, non-toxic, antiviral, fungistatic, etc. Biopolymers of natural origin tend to be similar, often almost identical, to tissues and macromolecular substances that the biological environment can recognize and metabolize. This presents a great advantage, since they could avoid problems derived from toxicity and production of the known "foreign body reaction". As biodegradable materials, these provide the proper biological environment and improve the cellular response, although its mechanical properties are not as good as those of synthetic materials. The high biodegradability of these materials facing enzymes of living organisms, ensures that as an implant will be metabolized by physiological mechanisms. That makes a lot of sense when talking about drug delivery since the idea isto introduce a drug inside a biopolymer and while it degrades the drug is being dosed constantly. The degradation speed can be modified according to the use that is wanted to be given to the biomaterial (Sastre, de Aza, & San Román, 2004). First, the information that can be found is about the polymers that will be used to coat the nanoparticles: Alginate and Chitosan. Straightaway, information about the materials for the nanoparticles will be found. Finally, information about drug delivery systems and the techniques to create the nanoparticles will be found in the following sections.

[ES] En el presente trabajo la alumna realizará síntesis de nanoparticulas polimericas (PLGA-Alginato y Fe-CS) mediante una técnica de nanoprecipitación con la finalidad de obtener partículas nanométricas y se obtendrá una caracterización a fondo de estas mismas. Tras esto se analizará la encapsulación de un colorante para realizar un estudio sobre cuan factible es esta técnica para la inicial hipotesis de encapsular un farmaco de caracteristicas similares al colorante. Y por ultimo, se encapsulará el fármaco y se hará un estudio de degradación y de liberación del fármaco en cuestión., [EN] Since the present, trend points to an increasing interest in the use of natural ingredients in food, drugs, and cosmetics(Tønnesen & Karlsen, 2002).Therefore, the use of biodegradable polymers, in the aforementioned applications have pushed research into working with them. Natural polymers, biopolymers, have advantages such as they are non-allergic, non-toxic, antiviral, fungistatic, etc. Biopolymers of natural origin tend to be similar, often almost identical, to tissues and macromolecular substances that the biological environment can recognize and metabolize. This presents a great advantage, since they could avoid problems derived from toxicity and production of the known "foreign body reaction". As biodegradable materials, these provide the proper biological environment and improve the cellular response, although its mechanical properties are not as good as those of synthetic materials. The high biodegradability of these materials facing enzymes of living organisms, ensures that as an implant will be metabolized by physiological mechanisms. That makes a lot of sense when talking about drug delivery since the idea isto introduce a drug inside a biopolymer and while it degrades the drug is being dosed constantly. The degradation speed can be modified according to the use that is wanted to be given to the biomaterial (Sastre, de Aza, & San Román, 2004). First, the information that can be found is about the polymers that will be used to coat the nanoparticles: Alginate and Chitosan. Straightaway, information about the materials for the nanoparticles will be found. Finally, information about drug delivery systems and the techniques to create the nanoparticles will be found in the following sections.

[ES] En el presente trabajo la alumna realizará síntesis de nanoparticulas polimericas (PLGA-Alginato y Fe-CS) mediante una técnica de nanoprecipitación con la finalidad de obtener partículas nanométricas y se obtendrá una caracterización a fondo de estas mismas. Tras esto se analizará la encapsulación de un colorante para realizar un estudio sobre cuan factible es esta técnica para la inicial hipotesis de encapsular un farmaco de caracteristicas similares al colorante. Y por ultimo, se encapsulará el fármaco y se hará un estudio de degradación y de liberación del fármaco en cuestión., [EN] Since the present, trend points to an increasing interest in the use of natural ingredients in food, drugs, and cosmetics(Tønnesen & Karlsen, 2002).Therefore, the use of biodegradable polymers, in the aforementioned applications have pushed research into working with them. Natural polymers, biopolymers, have advantages such as they are non-allergic, non-toxic, antiviral, fungistatic, etc. Biopolymers of natural origin tend to be similar, often almost identical, to tissues and macromolecular substances that the biological environment can recognize and metabolize. This presents a great advantage, since they could avoid problems derived from toxicity and production of the known "foreign body reaction". As biodegradable materials, these provide the proper biological environment and improve the cellular response, although its mechanical properties are not as good as those of synthetic materials. The high biodegradability of these materials facing enzymes of living organisms, ensures that as an implant will be metabolized by physiological mechanisms. That makes a lot of sense when talking about drug delivery since the idea isto introduce a drug inside a biopolymer and while it degrades the drug is being dosed constantly. The degradation speed can be modified according to the use that is wanted to be given to the biomaterial (Sastre, de Aza, & San Román, 2004). First, the information that can be found is about the polymers that will be used to coat the nanoparticles: Alginate and Chitosan. Straightaway, information about the materials for the nanoparticles will be found. Finally, information about drug delivery systems and the techniques to create the nanoparticles will be found in the following sections.

Composite hydrogels capable of controlled drug delivery via ion exchange are an interesting group of materials for the construction of implantable drug reservoirs for electrically charged drugs. In this study, we synthesized composite poly(DL-lactide-co-glycolide)/poly(acrylic acid) (PLGA-PAA) hydrogels by sequential application of UV or gamma irradiation and traditional phase inversion. Physicochemical properties of the composite PLGAPAA hydrogels were investigated using Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). We examined the ion exchange capacity (IEC) and swelling behavior of these materials to determine their potential as drug reservoirs. Composite PLGA-PAA hydrogel synthesized using UV irradiation (UV-PLGA-PAA) exhibited a porous microstructure with submicron-sized hydrogel-rich aggregates and homogeneous chemical composition. Swelling behavior and IEC of this material were highly reproducible. Composite PLGA-PAA hydrogels synthesized using gamma irradiation (G-PLGA-PAAs) had a less uniform microstructure with larger pores and micron-sized hydrogel-rich aggregates while exhibiting rather inhomogeneous chemical composition. These materials showed superior swelling properties, but a more variable IEC, compared to the material fabricated using UV irradiation. Results of DSC analysis showed a dose-dependent decrease in glass transition temperature for G-PLGA-PAAs indicating the effects of PLGA chain scission. Our findings indicate that gamma irradiation is a possible alternative to UV irradiation in the synthesis of composite PLGA-PAA hydrogels which can modify or control important material properties. However, the synthesis protocol using gamma irradiation should be further optimized to improve the IEC reproducibility. In our future research, we will investigate the in vitro release of charged drugs from synthesized composite PLGA-PAA hydr

Nanofibrous biomaterials have huge potential for drug delivery, due to their structural features and functions that are similar to the native extracellular matrix (ECM). A wide range of natural and polymeric materials can be employed to produce nanofibrous biomaterials. This review introduces the major natural and synthetic biomaterials for production of nanofibers that are biocompatible and biodegradable. Different technologies and their corresponding advantages and disadvantages for manufacturing nanofibrous biomaterials for drug delivery were also reported. The morphologies and structures of nanofibers can be tailor-designed and processed by carefully selecting suitable biomaterials and fabrication methods, while the functionality of nanofibrous biomaterials can be improved by modifying the surface. The loading and releasing of drug molecules, which play a significant role in the effectiveness of drug delivery, are also surveyed. This review provides insight into the fabrication of functional polymeric nanofibers for drug delivery.

Composite hydrogels capable of controlled drug delivery via ion exchange are an interesting group of materials for the construction of implantable drug reservoirs for electrically charged drugs. In this study, we synthesized composite poly(DL-lactide-co-glycolide)/poly(acrylic acid) (PLGA-PAA) hydrogels by sequential application of UV or gamma irradiation and traditional phase inversion. Physicochemical properties of the composite PLGA-PAA hydrogels were investigated using Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). We examined the ion exchange capacity (IEC) and swelling behavior of these materials to determine their potential as drug reservoirs. Composite PLGA-PAA hydrogel synthesized using UV irradiation (UV-PLGA-PAA) exhibited a porous microstructure with submicron-sized hydrogel-rich aggregates and homogeneous chemical composition. Swelling behavior and IEC of this material were highly reproducible. Composite PLGA-PAA hydrogels synthesized using gamma irradiation (G-PLGA-PAAs) had a less uniform microstructure with larger pores and micron-sized hydrogel-rich aggregates while exhibiting rather inhomogeneous chemical composition. These materials showed superior swelling properties, but a more variable IEC, compared to the material fabricated using UV irradiation. Results of DSC analysis showed a dose-dependent decrease in glass transition temperature for G-PLGA-PAAs indicating the effects of PLGA chain scission. Our findings indicate that gamma irradiation is a possible alternative to UV irradiation in the synthesis of composite PLGA-PAA hydrogels which can modify or control important material properties. However, the synthesis protocol using gamma irradiation should be further optimized to improve the IEC reproducibility. In our future research, we will investigate the in vitro release of charged drugs from synthesized composite PLGA-PAA hyd

Composite hydrogels capable of controlled drug delivery via ion exchange are an interesting group of materials for the construction of implantable drug reservoirs for electrically charged drugs. In this study, we synthesized composite poly(DL-lactide-co-glycolide)/poly(acrylic acid) (PLGA-PAA) hydrogels by sequential application of UV or gamma irradiation and traditional phase inversion. Physicochemical properties of the composite PLGA-PAA hydrogels were investigated using Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). We examined the ion exchange capacity (IEC) and swelling behavior of these materials to determine their potential as drug reservoirs. Composite PLGA-PAA hydrogel synthesized using UV irradiation (UV-PLGA-PAA) exhibited a porous microstructure with submicron-sized hydrogel-rich aggregates and homogeneous chemical composition. Swelling behavior and IEC of this material were highly reproducible. Composite PLGA-PAA hydrogels synthesized using gamma irradiation (G-PLGA-PAAs) had a less uniform microstructure with larger pores and micron-sized hydrogel-rich aggregates while exhibiting rather inhomogeneous chemical composition. These materials showed superior swelling properties, but a more variable IEC, compared to the material fabricated using UV irradiation. Results of DSC analysis showed a dose-dependent decrease in glass transition temperature for G-PLGA-PAAs indicating the effects of PLGA chain scission. Our findings indicate that gamma irradiation is a possible alternative to UV irradiation in the synthesis of composite PLGA-PAA hydrogels which can modify or control important material properties. However, the synthesis protocol using gamma irradiation should be further optimized to improve the IEC reproducibility. In our future research, we will investigate the in vitro release of charged drugs from synthesized composite PLGA-PAA hyd

Composite hydrogels capable of controlled drug delivery via ion exchange are an interesting group of materials for the construction of implantable drug reservoirs for electrically charged drugs. In this study, we synthesized composite poly(DL-lactide-co-glycolide)/poly(acrylic acid) (PLGA-PAA) hydrogels by sequential application of UV or gamma irradiation and traditional phase inversion. Physicochemical properties of the composite PLGA-PAA hydrogels were investigated using Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). We examined the ion exchange capacity (IEC) and swelling behavior of these materials to determine their potential as drug reservoirs. Composite PLGA-PAA hydrogel synthesized using UV irradiation (UV-PLGA-PAA) exhibited a porous microstructure with submicron-sized hydrogel-rich aggregates and homogeneous chemical composition. Swelling behavior and IEC of this material were highly reproducible. Composite PLGA-PAA hydrogels synthesized using gamma irradiation (G-PLGA-PAAs) had a less uniform microstructure with larger pores and micron-sized hydrogel-rich aggregates while exhibiting rather inhomogeneous chemical composition. These materials showed superior swelling properties, but a more variable IEC, compared to the material fabricated using UV irradiation. Results of DSC analysis showed a dose-dependent decrease in glass transition temperature for G-PLGA-PAAs indicating the effects of PLGA chain scission. Our findings indicate that gamma irradiation is a possible alternative to UV irradiation in the synthesis of composite PLGA-PAA hydrogels which can modify or control important material properties. However, the synthesis protocol using gamma irradiation should be further optimized to improve the IEC reproducibility. In our future research, we will investigate the in vitro release of charged drugs from synthesized composite PLGA-PAA hyd