Monoclonal Antibodies for the Treatment of Ocular Diseases.

Monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy, offering unprecedented specificity and diverse mechanisms to combat malignant cells. These biologic agents have emerged as a cornerstone in targeted cancer treatment, binding to specific antigens on cancer cells and exerting their therapeutic effects through various mechanisms, including inhibition of signaling pathways, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). The unique ability of mAbs to engage the immune system and directly interfere with cancer cell function has significantly enhanced the therapeutic armamentarium against a broad spectrum of malignancies. mAbs were initially studied in oncology; however, today, treatments have been developed for eye diseases. This review discusses the current applications of mAbs for the treatment of ocular diseases, discussing the specificity and the variety of mechanisms by which these molecules exhibit their therapeutic effects. The benefits, drawbacks, effectiveness, and risks associated with using mAbs in ophthalmology are highlighted, focusing on the most relevant ocular diseases and mAbs currently in use. Technological advances have led to in vitro production methods and recombinant engineering techniques, allowing the development of chimeric, humanized, and fully human mAbs. Nowadays, many humanized mAbs have several applications, e.g., for the treatment of age-related macular disease, diabetic retinopathy, and uveitis, while studies about new applications of mAbs, such as for SARS-CoV-2 infection, are also currently ongoing to seek more efficient and safe approaches to treat this new ocular disease.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the delivery of bioactives sourced from plants: part II - applications and preclinical advancements.

INTRODUCTION: Numerous purified bioactive compounds, crude extracts, and essential oils have demonstrated potent antioxidant, antimicrobial, anti-inflammatory, and antiviral properties, particularly in vitro or in silico; however, their in vivo applications are hindered by inadequate absorption and distribution in the organism. The incorporation of these phytochemicals into solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) has demonstrated significant advancements and represents a viable approach to improve their bioavailability through different administration routes. AREAS COVERED: This review discusses the potential applications of SLN and NLC, loading bioactive compounds sourced from plants for the treatment of several diseases. An overview of the preclinical developments on the use of these lipid nanoparticles is also provided as well as the requisites to be launched on the market. EXPERT OPINION: Medicinal plants have gained even more value for the pharmaceutical industries and their customers, leading to many studies exploring their therapeutic potential. Several bioactives derived from plants with antiviral, anticancer, neuroprotective, antioxidant, and antiaging properties have been proposed and loaded into lipid nanoparticles. In vitro and invivo studies corroborate the added value of SLN/NLC to improve the bioavailability of several bioactives. Surface modification to increase their stability and target delivery should be considering.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the delivery of bioactives sourced from plants: part I - composition and production methods.

INTRODUCTION: Nanoparticles (NPs) are widely used in the pharmaceutical field to treat various human disorders. Among these, lipid-based NPs (LNPs), including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), are favored for drug/bioactive delivery due to their high stability, biocompatibility, encapsulation efficiency, and sustained/controlled release. These properties make them particularly suitable as carriers of compounds derived from plant sources. AREAS COVERED: This study comprehensively explores updated literature knowledge on SLN and NLC, focusing on their composition and production methods for the specific delivery of drug/bioactive compounds derived from plant sources of interest in pharmaceutical and biomedical fields. EXPERT OPINION: SLN and NLC facilitate the development of more effective natural product-based therapies, aiming to reduce dosage and minimize side effects. These delivery systems align with the consumer demands for safer and more sustainable products, as there are also based on biocompatible and biodegradable raw materials, thereby posing minimal toxicological risks while also meeting regulatory guidelines.

Caspofungin formulations for buccal and sublingual mucosae anti-fungal infections: physicochemical characterization, rheological analysis, release and ex vivo permeability profiles.

AIM: Oral candidiasis is often challenging due to limited effectiveness of topical treatments. This study aimed to develop novel caspofungin formulations for administration onto the oral mucosa to enhance drug retention and efficacy. METHOD: Five caspofungin (2%, w/v) formulations were developed to assess their permeability, retention and mucoadhesiveness. Ex vivo permeability assays were performed on buccal and sublingual mucosae, and histological analyses conducted to evaluate tissue tolerance. RESULTS: Formulation composed of chitosan demonstrated the highest retention in both buccal (5183.24 ± 587.32 µg/cm2) and sublingual (1090.72 ± 110.26 µg/cm2) mucosae. Other formulations exhibited significantly lower retention, ranging from 7.53 ± 0.81 to 1852.10 ± 193.24 µg/cm2 in buccal mucosa and 1.64 ± 0.14 to 317.74 ± 31.78 µg/cm2 in sublingual mucosa. Chitosan-based formulation exhibited the highest mucoadhesive strength, with values of 5179.05 ± 31.99 mN/cm2 for buccal and 7026.10 ± 123.41 mN/cm2 for sublingual mucosae, and also superior extensibility, which facilitates application in the oral cavity. All formulations showed antifungal activity against Candida spp., and histological analyses revealed minor epithelial alterations. CONCLUSION: The developed formulations offer distinct advantages for treating oral candidiasis, with chitosan formulation emerging as the most promising due to its superior retention, mucoadhesion force, and spreadability, making it a potential candidate for further clinical investigation.

Dual Chemotherapeutic Loading in Oxalate Transferrin-Conjugated Polymersomes Incorporated into Chitosan Hydrogels for Site-Specific Targeting of Melanoma Cells.

In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the oxalate transferrin variant (oxalate Tf) and incorporated into three-dimensional chitosan hydrogels. This innovative approach represents the first application of oxalate Tf for the precision delivery of drug-loaded polymersomes within a semi-solid dosage form based on chitosan hydrogels. These resulting semi-solids exhibited a sustained release profile for both encapsulated drugs. To evaluate their potency, we compared the cytotoxicity of native Tf-Ps with oxalate Tf-Ps. Notably, the oxalate Tf-Ps demonstrated a 3-fold decrease in cell viability against melanoma cells compared to normal cells and were 1.6-fold more potent than native Tf-Ps, indicating the greater potency of this nanoformulation. These findings suggest that dual-drug delivery using an oxalate-Tf-targeting ligand significantly enhances the drug delivery efficiency of Tf-conjugated nanovesicles and offers a promising strategy to overcome the challenge of multidrug resistance in melanoma therapy.

A Newly Validated HPLC-DAD Method for the Determination of Ricinoleic Acid (RA) in PLGA Nanocapsules.

The assessment of ricinoleic acid (RA) incorporated into polymeric nanoparticles is a challenge that has not yet been explored. This bioactive compound, the main component of castor oil, has attracted attention in the pharmaceutical field for its valuable anti-inflammatory, antifungal, and antimicrobial properties. This work aims to develop a new and simple analytical method using high-performance liquid chromatography with diode-array detection (HPLC-DAD) for the identification and quantification of ricinoleic acid, with potential applicability in several other complex systems. The method was validated through analytical parameters, such as linearity, limit of detection and quantification, accuracy, precision, selectivity, and robustness. The physicochemical properties of the nanocapsules were characterized by dynamic light scattering (DLS) to determine their hydrodynamic mean diameter, polydispersity index (PDI), and zeta potential (ZP), via transmission electron microscopy (TEM) and quantifying the encapsulation efficiency. The proposed analytical method utilized a mobile phase consisting of a 65:35 ratio of acetonitrile to water, acidified with 1.5% phosphoric acid. It successfully depicted a symmetric peak of ricinoleic acid (retention time of 7.5 min) for both the standard and the RA present in the polymeric nanoparticles, enabling the quantification of the drug loaded into the nanocapsules. The nanocapsules containing ricinoleic acid (RA) exhibited an approximate size ranging from 309 nm to 441 nm, a PDI lower than 0.2, ζ values of approximately -30 mV, and high encapsulation efficiency (~99%). Overall, the developed HPLC-DAD procedure provides adequate confidence for the identification and quantification of ricinoleic acid in PLGA nanocapsules and other complex matrices.

Biodegradable nanoplatforms for antigen delivery: part II - nanoparticles, hydrogels, and microneedles for cancer immunotherapy.

INTRODUCTION: In recent years, chimeric antigen receptor T (CAR-T) cell therapy has resulted in a breakthrough in the treatment of patients with refractory or relapsed hematological malignancies. However, the identification of patients suitable for CAR-T cell therapy needs to be improved. AREASCOVERED: CAR-T cell therapy has demonstrated excellent efficacy in hematological malignancies; however, views on determining when to apply CAR-T cells in terms of the evaluation of patient characteristics remain controversial. EXPERT OPINION: We reviewed the current feasibility and challenges of CAR-T cell therapy in the most common hematological malignancies and classified them according to disease type and treatment priority, to guide clinicians and researchers in applying and investigating CAR-T cells further.

Biodegradable nanoplatforms for antigen delivery: part I - state of the art review of polymeric nanoparticles for cancer immunotherapy.

INTRODUCTION: Polymeric nanoparticles used for antigen delivery against infections and for cancer immunotherapy are an emerging therapeutic strategy in promoting the development of innovative vaccines. Beyond their capability to create targeted delivery systems with controlled release of payloads, biodegradable polymers are utilized for their ability to enhance the immunogenicity and stability of antigens. AREAS COVERED: This review extensively discusses the physicochemical parameters that affect the behavior of nanoparticles as antigen-delivery systems. Additionally, various types of natural and synthetic polymers and recent advancements in nanoparticle-based targeted vaccine production are reviewed. EXPERT OPINION: Biodegradable polymeric nanoparticles have gained major interest in the vaccination filed and have been extensively used to encapsulate antigens against a wide variety of tumors. Moreover, their versatility in terms of tunning their physicochemical characteristics, and their surface, facilitates the targeting to antigen presenting cells and enhances immune response.

Antitumoral melatonin-loaded nanostructured lipid carriers.

Aim: Cancer constitutes the second leading cause of death worldwide, with conventional therapies limited by significant side effects. Melatonin (MEL), a natural compound with antitumoral properties, suffers from instability and low solubility. To overcome these issues, MEL was encapsulated into nanostructured lipid carriers (MEL-NLC) containing rosehip oil to enhance stability and boost its antitumoral activity.Methods: MEL-NLC were optimized by a design of experiments approach and characterized for their physicochemical properties. Stability and biopharmaceutical behavior were assessed, along with interaction studies and in vitro antitumoral efficacy against various cancer cell lines.Results: Optimized MEL-NLC exhibited desirable physicochemical characteristics, including small particle size and sustained MEL release, along with long-term stability. In vitro studies demonstrated that MEL-NLC selectively induced cytotoxicity in several cancer cell lines while sparing healthy cells.Conclusion: MEL-NLC represent a promising alternative for cancer, combining enhanced stability and targeted antitumoral activity, potentially overcoming the limitations of conventional treatments.

Despite current advances, cancer is the second cause of death worldwide, but conventional therapies have side effects and limited efficacy. Natural therapies are emerging as suitable alternatives and, among them, Melatonin is a well-known compound with antitumoral properties. However, it is degraded by light, decreasing its therapeutical activity. In order to effectively deliver Melatonin into cancer cells, it has been encapsulated into biodegradable nanoparticles containing rosehip oil, which may boost the antitumoral properties. These nanoparticles have been optimized, showing a small size and a high Melatonin encapsulation, sustained drug release and good stability. Furthermore, in vitro studies demonstrated antitumoral activity against several cancer cell lines, also showing a high internalization inside them. Moreover, studies conducted using chicken embryonated eggs, showed that nanoparticles were non-toxic, thus confirming its promising therapeutical applications.

Next-generation pediatric care: nanotechnology-based and AI-driven solutions for cardiovascular, respiratory, and gastrointestinal disorders.

BACKGROUND: Global pediatric healthcare reveals significant morbidity and mortality rates linked to respiratory, cardiac, and gastrointestinal disorders in children and newborns, mostly due to the complexity of therapeutic management in pediatrics and neonatology, owing to the lack of suitable dosage forms for these patients, often rendering them "therapeutic orphans". The development and application of pediatric drug formulations encounter numerous challenges, including physiological heterogeneity within age groups, limited profitability for the pharmaceutical industry, and ethical and clinical constraints. Many drugs are used unlicensed or off-label, posing a high risk of toxicity and reduced efficacy. Despite these circumstances, some regulatory changes are being performed, thus thrusting research innovation in this field. DATA SOURCES: Up-to-date peer-reviewed journal articles, books, government and institutional reports, data repositories and databases were used as main data sources. RESULTS: Among the main strategies proposed to address the current pediatric care situation, nanotechnology is specially promising for pediatric respiratory diseases since they offer a non-invasive, versatile, tunable, site-specific drug release. Tissue engineering is in the spotlight as strategy to address pediatric cardiac diseases, together with theragnostic systems. The integration of nanotechnology and theragnostic stands poised to refine and propel nanomedicine approaches, ushering in an era of innovative and personalized drug delivery for pediatric patients. Finally, the intersection of drug repurposing and artificial intelligence tools in pediatric healthcare holds great potential. This promises not only to enhance efficiency in drug development in general, but also in the pediatric field, hopefully boosting clinical trials for this population. CONCLUSIONS: Despite the long road ahead, the deepening of nanotechnology, the evolution of tissue engineering, and the combination of traditional techniques with artificial intelligence are the most recently reported strategies in the specific field of pediatric therapeutics.

Identification of microRNAs expressed in an animal model of periodontal disease and their impact on pathological processes.

MicroRNAs represent a class of small RNAs that act to silence genes post-transcriptionally by inhibiting the translation of target messenger RNAs, and this study aimed to understand how miRNAs influence the set-up of periodontal disease. Periodontitis was induced by inserting a ligature into the left first mandibular molar in a rat model, which was kept for the entire 56 days-time of experiment. After 56 days post-periodontitis induction, the histopathological analysis showed an apical extension of the junctional epithelium, with areas of hyperplasia, exocytosis, and a mixed inflammatory infiltrate with a predominance of neutrophils, lymphocytes, and eventual plasma cells in the deeper layers. The cement surface showed areas of irregularity, covered by cementoblasts and irregular surfaces, confirming the set-up of periodontitis. In the sequencing analysis, 26,404 genes were identified, with 132 reaching statistical significance. Among genes with a statistical difference, 18 were found to encode for microRNAs. The identified microRNAs are primarily involved in bone remodeling by acting on fibroblast growth factors, and collagen production. These outcomes demonstrate a signaling role in bone resorption, which is consistent with the histopathological observations that show the installation of inflammation with epithelial migration and the beginning of the repair process, with cementum resorption. The disclosure of how miRNAs may influence the maintaining of periodontal disease will help the development of new dental materials for the prophylaxis and treatment of alveolar bone resorption.

Combination of Indomethacin with Nanostructured Lipid Carriers for Effective Anticancer Therapy.

Purpose: The anticancer potential of indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, in vivo, and in clinical trials is well known and widely reported in the literature, along with their side effects, which are mainly observed in the gastrointestinal tract. Here, we present a strategy for the application of the old drug indomethacin as an anticancer agent by encapsulating it in nanostructured lipid carriers (NLC). We describe the production method of IND-NLC, their physicochemical parameters, and the results of their antiproliferative activity against selected cancer cell lines, which were found to be higher compared to the activity of free indomethacin. Methods: IND-NLC were fabricated using the hot high-pressure homogenization method. The nanocarriers were physicochemically characterized, and their biopharmaceutical behaviour and therapeutic efficacy were evaluated in vitro. Results: Lipid nanoparticles IND-NLC exhibited a particle size of 168.1 nm, a negative surface charge (-30.1 mV), low polydispersity index (PDI of 0.139), and high encapsulation efficiency (over 99%). IND-NLC were stable for over 60 days and retained integrity during storage at 4 °C and 25 °C. The potential therapeutic benefits of IND-NLC were screened using in vitro cancer models, where nanocarriers with encapsulated drug effectively inhibited the growth of breast cancer cell line MDA-MB-468 at dosage 15.7 µM. Conclusion: We successfully developed IND-NLC for delivery of indomethacin to cancer cells and confirmed their antitumoral efficacy in in vitro studies. The results suggest that indomethacin encapsulated in lipid nanoparticles possesses high anticancer potential. Moreover, the presented strategy is highly promising and may offer a new alternative for future therapeutic drug innovations.

Chitosan membranes incorporating Aloe vera glycolic extract with joint synthesis of silver nanoparticles for the treatment of skin lesions.

New wound dressings based on polymeric membranes have been widely exploited for clinical applications to assist in the healing process and prevent additional complications (e.g., bacterial infections). Here we propose the development of a new production method of polymeric membranes based on chitosan, incorporating glycolic extract of Aloe vera with joint synthesis of silver nanoparticles for use as a new bioactive dressing. The membranes were obtained by casting technique, and their morphological, physicochemical characteristics, degree of swelling, degradation profile and antimicrobial activity evaluated. Morphological analyzes confirmed the synthesis and presence of silver nanoparticles in the polymeric membrane. The chemical compatibility between the materials was demonstrated through thermal analysis (TGA and DSC) combined with ATR-FTIR tests, showing the complexation of the membranes (Mb-Ch-Ex.Av-NPs). All membranes were characterized as hydrophilic material (with a contact angle (Ó©) < 90°); however, the highest degree of swelling was obtained for the chitosan. (Mb-Ch) membrane (69.91 ± 5.75%) and the lowest for Mb-Ch-Ex.Av-NPs (26.62 ± 8.93%). On the other hand, the degradation profile was higher for Mb-Ch-Ex.Av-NPs (77.85 ± 7.51%) and lower for Mb-Ch (57.60 ± 2.29%). The manufactured bioactive dressings showed activity against Escherichia coli and Staphylococcus aureus. Our work confirmed the development of translucent and flexible chitosan-based membranes, incorporating Aloe vera glycolic extract with joint synthesis of silver nanoparticles for use as a new bioactive dressing, with proven antimicrobial activity.

Neuroprotective effects of Tradescantia spathacea tea bioactives in Parkinson's disease: In vivo proof-of-concept.

Background and aim: Tradescantia spathacea (T. spathacea) is a traditional medicinal plant from Central America and its tea, obtained by infusion, has been recognized as a functional food. The aim of this work was to investigate the effects of dry tea containing biocompounds from T. spathacea tea on motor and emotional behavior, as well as tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) expression in 6-hydroxydopamine (6-OHDA)-lesioned rats. Experimental procedure: Bioactives were identified by Ultra Performance Liquid Chromatography (UPLC) and an in vivo study in male Wistar rats was run as proof of concept of neuroprotective effects of DTTS. Results and conclusion: We found 15 biocompounds that had not been previously reported in T. spathacea: the UPLC-QTOF-MS/MS allowed identification five phenolic acids, one coumarin, two flavonoids, one iridoid, one phenylpropanoid glycoside, and six fatty acid derivatives. The dry tea of T. spathacea (DTTS) presented significant antioxidant activity and high contents of phenolic compounds and flavonoids. Doses of 10, 30, and 100 mg/kg of DTTS were protective against dopaminergic neurodegeneration and exhibited modulatory action on the astrocyte-mediated neuroinflammatory response. Behavioral tests showed that 30 mg/kg of DTTS counteracted motor impairment, while 100 mg/kg produced an anxiolytic effect. The DTTS could be, therefore, a promising strategy for the management of Parkinson's disease.

Natural antibiotics against antimicrobial resistance: sources and bioinspired delivery systems.

The current burden associated to multidrug resistance, and the emerging superbugs, result in a decreased and even loss of antibiotic efficacy, which poses significant challenges in the treatment of infectious diseases. This situation has created a high demand for the discovery of novel antibiotics that are both effective and safe. However, while antibiotics play a crucial role in preventing and treating diseases, they are also associated with adverse effects. The emergence of multidrug-resistant and the extensive appearance of drug-resistant microorganisms, has become one of the major hurdles in healthcare. Addressing this problem will require the development of at least 20 new antibiotics by 2060. However, the process of designing new antibiotics is time-consuming. To overcome the spread of drug-resistant microbes and infections, constant evaluation of innovative methods and new molecules is essential. Research is actively exploring alternative strategies, such as combination therapies, new drug delivery systems, and the repurposing of existing drugs. In addition, advancements in genomic and proteomic technologies are aiding in the identification of potential new drug targets and the discovery of new antibiotic compounds. In this review, we explore new sources of natural antibiotics from plants, algae other sources, and propose innovative bioinspired delivery systems for their use as an approach to promoting responsible antibiotic use and mitigate the spread of drug-resistant microbes and infections.

From Extraction to Stabilization: Employing a 22 Experimental Design in Developing Nutraceutical-Grade Bixin from Bixa orellana L.

Bixin is the main carotenoid found in the outer portion of the seeds of Bixa orellana L., commercially known as annatto. This compound is industrially employed in pharmaceutical, cosmetic, and food formulations as a natural dye to replace chemical additives. This study aimed to extract bixin from annatto seeds and obtain encapsulated bixin in a powder form, using freeze-drying encapsulation and maltodextrin as encapsulating agent. Bixin was extracted from annatto seeds employing successive washing with organic solvents, specifically hexane and methanol (1:1 v/v), followed by ethyl acetate and dichloromethane for subsequent washes, to effectively remove impurities and enhance bixin purity, and subsequent purification by crystallization, reaching 1.5 ± 0.2% yield (or approximately 15 mg of bixin per gram of seeds). Bixin was analyzed spectrophotometrically in different organic solvents (ethanol, isopropyl alcohol, dimethylsulfoxide, chloroform, hexane), and the solvents chosen were chloroform (used to solubilize bixin during microencapsulation) and hexane (used for spectrophotometric determination of bixin). Bixin was encapsulated according to a 22 experimental design to investigate the influence of the concentration of maltodextrin (20 to 40%) and bixin-to-matrix ratio (1:20 to 1:40) on the encapsulation efficiency (EE%) and solubility of the encapsulated powder. Higher encapsulation efficiency was obtained at a maltodextrin concentration of 40% w/v and a bixin/maltodextrin ratio of 1:20, while higher solubility was observed at a maltodextrin concentration of 20% w/v for the same bixin/maltodextrin ratio. The encapsulation of this carotenoid by means of freeze-drying is thus recognized as an innovative and promising approach to improve its stability for further processing in pharmaceutical and food applications.

Regulatory insights into nanomedicine and gene vaccine innovation: Safety assessment, challenges, and regulatory perspectives.

This analysis explores the principal regulatory concerns linked to nanomedicines and gene vaccines, including the complexities involved and the perspectives on how to navigate them. In the realm of nanomedicines, ensuring the safety of nanomaterials is paramount due to their unique characteristics and potential interactions with biological systems. Regulatory bodies are actively formulating guidelines and standards to assess the safety and risks associated with nanomedicine products, emphasizing the need for standardized characterization techniques to accurately gauge their safety and effectiveness. Regarding gene vaccines, regulatory frameworks must be tailored to address the distinct challenges posed by genetic interventions, necessitating special considerations in safety and efficacy evaluations, particularly concerning vector design, target specificity, and long-term patient monitoring. Ethical concerns such as patient autonomy, informed consent, and privacy also demand careful attention, alongside the intricate matter of intellectual property rights, which must be balanced against the imperative of ensuring widespread access to these life-saving treatments. Collaborative efforts among regulatory bodies, researchers, patent offices, and the private sector are essential to tackle these challenges effectively, with international cooperation being especially crucial given the global scope of nanomedicine and genetic vaccine development. Striking the right balance between safeguarding intellectual properties and promoting public health is vital for fostering innovation and ensuring equitable access to these ground-breaking technologies, underscoring the significance of addressing these regulatory hurdles to fully harness the potential benefits of nanomedicine and gene vaccines for enhancing healthcare outcomes on a global scale. STATEMENT OF SIGNIFICANCE: Several biomaterials are being proposed for the development of nanovaccines, from polymeric micelles, PLGA-/PEI-/PLL-nanoparticles, solid lipid nananoparticles, cationic lipoplexes, liposomes, hybrid materials, dendrimers, carbon nanotubes, hydrogels, to quantum dots. Lipid nanoparticles (LNPs) have gained tremendous attention since the US Food and Drug Administration (FDA) approval of Pfizer and Moderna's COVID-19 vaccines, raising public awareness to the regulatory challenges associated with nanomedicines and genetic vaccines. This review provides insights into the current perspectives and potential strategies for addressing these issues, including clinical trials. By navigating these regulatory landscapes effectively, we can unlock the full potential of nanomedicine and genetic vaccines using a range of promising biomaterials towards improving healthcare outcomes worldwide.

Human mesenchymal stromal cells-laden crosslinked hyaluronic acid-alginate bioink for 3D bioprinting applications in tissue engineering.

Three-dimensional (3D) bioprinting is considered one of the most advanced tools to build up materials for tissue engineering. The aim of this work was the design, development and characterization of a bioink composed of human mesenchymal stromal cells (hMSC) for extrusion through nozzles to create these 3D structures that might potentially be apply to replace the function of damaged natural tissue. In this study, we focused on the advantages and the wide potential of biocompatible biomaterials, such as hyaluronic acid and alginate for the inclusion of hMSC. The bioink was characterized for its physical (pH, osmolality, degradation, swelling, porosity, surface electrical properties, conductivity, and surface structure), mechanical (rheology and printability) and biological (viability and proliferation) properties. The developed bioink showed high porosity and high swelling capacity, while the degradation rate was dependent on the temperature. The bioink also showed negative electrical surface and appropriate rheological properties required for bioprinting. Moreover, stress-stability studies did not show any sign of physical instability. The developed bioink provided an excellent environment for the promotion of the viability and growth of hMSC cells. Our work reports the first-time study of the effect of storage temperature on the cell viability of bioinks, besides showing that our bioink promoted a high cell viability after being extruded by the bioprinter. These results support the suggestion that the developed hMSC-composed bioink fulfills all the requirements for tissue engineering and can be proposed as a biological tool with potential applications in regenerative medicine and tissue engineering.

Psidium guajava L. phenolic compound-reinforced lamellar scaffold for tracheal tissue engineering.

The aim of this work was to develop a dense lamellar scaffold, as a biomimetic material with potential applications in the regeneration of tracheal tissue after surgical tumor resection. The scaffolds were produced by plastic compression technique, exploiting the use of total phenolic compounds (TPC) from Psidium guajava Linn as a potential cross-linking agent in a polymeric mixture based on collagen (COL), silk fibroin (SF), and polyethylene glycol 400 (PEG 400). Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) confirmed the chemical interactions between the polymers and the cross-linking of TPC between COL and SF. Morphological analyses showed scaffolds with porosity, interconnectivity, and a porous surface structure with a gyroid-like geometry. The analysis of the anisotropic degree resulted in anisotropic structures (0.1% TFC and 0.3% TFC) and an isotropic structure (0.5% TFC). In the mechanical properties, it was evidenced greater resistance for the 0.3% TFC formulation. The addition of TPC percentages did not result in a significant difference (p > 0.05) in swelling capacity and disintegration rate. The results confirmed that TPC were able to modulate the morphological, morphometric, and mechanical properties of scaffolds. Thus, this study describes a potential new material to improve the regeneration of major tracheal structures after surgical tumor removal.