Nanovaccines: Immunogenic tumor antigens, targeted delivery, and combination therapy to enhance cancer immunotherapy.

Nanovaccines have been designed to overcome the limitations associated with conventional vaccines. Effective delivery methods such as engineered carriers or smart nanoparticles (NPs) are critical requisites for inducing self-tolerance and optimizing vaccine immunogenicity with minimum side effects. NPs can be used as adjuvants, immunogens, or nanocarriers to develop nanovaccines for efficient antigen delivery. Multiloaded nanovaccines carrying multiple tumor antigens along with immunostimulants can effectively increase immunity against tumor cells. They can be biologically engineered to boost interactions with dendritic cells and to allow a gradual and constant antigen release. Modifying NPs surface properties, using high-density lipoprotein-mimicking nanodiscs, and developing nano-based artificial antigen-presenting cells such as dendritic cell-derived-exosomes are amongst the new developed technologies to enhance antigen-presentation and immune reactions against tumor cells. The present review provides an overview on the different perspectives, improvements, and barriers of successful clinical application of current cancer therapeutic and vaccination options. The immunomodulatory effects of different types of nanovaccines and the nanoparticles incorporated into their structure are described. The advantages of using nanovaccines to prevent and treat common illnesses such as AIDS, malaria, cancer and tuberculosis are discussed. Further, potential paths to develop optimal cancer vaccines are described. Given the immunosuppressive characteristics of both cancer cells and the tumor microenvironment, applying immunomodulators and immune checkpoint inhibitors in combination with other conventional anticancer therapies are necessary to boost the effectiveness of the immune response.

Enhanced wound healing properties of biodegradable PCL/alginate core-shell nanofibers containing Salvia abrotanoides essential oil and ZnO nanoparticles.

Electrospun nanofibrous membranes, with their unique structural features, can potentially enhance wound healing through controlled delivery of active agents. Here, an innovative porous nanofibrous membrane was developed as a dressing patch with antibacterial and anti-inflammatory functionalities for cutaneous wound healing. Zinc oxide nanoparticles (ZnO NPs) and Salvia abrotanoides essential oil (SAEO) were incorporated into sodium alginate, which served as the shell. Poly(ε-caprolactone) was used as the core of coaxial electrospun wound dressing nanofibers (PCL/SA@ZnO/SAEO). With the addition of ZnO NPs and SAEO, the average diameter of nanofibers was 187 ± 51 nm, with improved tensile strength (4.7 ± 0.4 MPa), elongation at break (32.9 ± 2.1), and elastic modulus (21.4 ± 2.0). Concurrent application of ZnO NPs and SAEO increased antimicrobial activity against Staphylococcus aureus and Escherichia coli and promoted the proliferation, attachment, and viability (>90 %) of L929 cells. The PCL/SA@ZnO/SAEO scaffold accelerated the healing time with total wound healing over 14 days in mouse models carrying full-thickness wounds compared to the nanofibrous scaffold without additives. Histopathological examinations demonstrated better tissue regeneration, i.e., enhanced collagen deposition, improved re-epithelialization, and neovascularization, and increased quantity of hair follicles. Moreover, the chicken chorioallantoic membrane assay confirmed the synergistic angiogenic effects of SAEO and ZnO NPs. Finally, the in vitro and in vivo results proposed the bioactive core-shell nanofibers synthesized as encouraging wound dressing materials for hastening the healing of cutaneous wounds.

A comprehensive overview on the crosstalk between microRNAs and viral pathogenesis and infection.

Infections caused by viruses as the smallest infectious agents, pose a major threat to global public health. Viral infections utilize different host mechanisms to facilitate their own propagation and pathogenesis. MicroRNAs (miRNAs), as small noncoding RNA molecules, play important regulatory roles in different diseases, including viral infections. They can promote or inhibit viral infection and have a pro-viral or antiviral role. Also, viral infections can modulate the expression of host miRNAs. Furthermore, viruses from different families evade the host immune response by producing their own miRNAs called viral miRNAs (v-miRNAs). Understanding the replication cycle of viruses and their relation with host miRNAs and v-miRNAs can help to find new treatments against viral infections. In this review, we aim to outline the structure, genome, and replication cycle of various viruses including hepatitis B, hepatitis C, influenza A virus, coronavirus, human immunodeficiency virus, human papillomavirus, herpes simplex virus, Epstein-Barr virus, Dengue virus, Zika virus, and Ebola virus. We also discuss the role of different host miRNAs and v-miRNAs and their role in the pathogenesis of these viral infections.

Stimuli-responsive nanotheranostic systems conjugated with AIEgens for advanced cancer bio-imaging and treatment.

Aggregation-induced emission (AIE) is a unique phenomenon observed in various materials such as organic luminophores, carbon dots (CDs), organic-inorganic nanocomposites, fluorescent dye molecules, and nanoparticles (NPs). These AIE-active materials, or AIEgens, are ideal for balancing multifunctional phototheranostics and energy dissipation. AIE properties can manifest in organic fluorescent probes, rendering them effective for cancer treatment due to their ability to penetrate deeply and provide high therapeutic efficacy. This efficacy is attributed to their high photobleaching thresholds, ability to induce Stokes shifts, and capacity to activate fluorophores. Therefore, the development of innovative AIE-based materials for disease diagnosis and treatment, particularly for cancer, is both important and promising. Recent years have seen successful demonstrations of nanoparticles with AIE properties being used for photodynamic therapy (PDT) and multimodal imaging of tumor cells. These fluorophores have been shown to impact mitochondria and lysosomes, generate reactive oxygen species (ROS), activate the immune system, load and release drugs, and ultimately induce apoptosis in tumor cells. In this review, we examine previous studies on the manufacturing methods and effects of AIEgens on cancer cells, with a theranostic strategy of simultaneous treatment and imaging. We also investigate the factors affecting drug delivery on different cancer cells, including internal stimuli such as pH, ROS, enzymes, and external stimuli like near-infrared (NIR) light and ultrasound waves.

Recent advances in gene delivery nanoplatforms based on spherical nucleic acids.

Gene therapy is a therapeutic option for mitigating diseases that do not respond well to pharmacological therapy. This type of therapy allows for correcting altered and defective genes by transferring nucleic acids to target cells. Notably, achieving a desirable outcome is possible by successfully delivering genetic materials into the cell. In-vivo gene transfer strategies use two major classes of vectors, namely viral and nonviral. Both of these systems have distinct pros and cons, and the choice of a delivery system depends on therapeutic objectives and other considerations. Safe and efficient gene transfer is the main feature of any delivery system. Spherical nucleic acids (SNAs) are nanotechnology-based gene delivery systems (i.e., non-viral vectors). They are three-dimensional structures consisting of a hollow or solid spherical core nanoparticle that is functionalized with a dense and highly organized layer of oligonucleotides. The unique structural features of SNAs confer them a high potency in internalization into various types of tissue and cells, a high stability against nucleases, and efficay in penetrating through various biological barriers (such as the skin, blood-brain barrier, and blood-tumor barrier). SNAs also show negligible toxicity and trigger minimal immune response reactions. During the last two decades, all these favorable physicochemical and biological attributes have made them attractive vehicles for drug and nucleic acid delivery. This article discusses the unique structural properties, types of SNAs, and also optimization mechanisms of SNAs. We also focus on recent advances in the synthesis of gene delivery nanoplatforms based on the SNAs.

Fabrication, Characterization and Wound-Healing Properties of Core-Shell SF@chitosan/ZnO/Astragalus Arbusculinus Gum Nanofibers.

AIM: Silk fibroin/chitosan/ZnO/Astragalus arbusculinus (Ast) gum fibrous scaffolds along with adipose-derived mesenchymal stem cells (ADSCs) were investigated for accelerating diabetic wound healing. METHODS: Scaffolds with a core-shell structure and different compositions were synthesized using the electrospinning method. Biological in vitro investigations included antibacterial testing, cell viability analysis and cell attachment evaluation. In vivo experiments, including the chicken chorioallantoic membrane (CAM) test, were conducted to assess wound-healing efficacy and histopathological changes. RESULTS: The incorporation of Ast to the silk fibroin@ chitosan/ZnO scaffold improved wound healing in diabetic mice. In addition, seeding of ADSCs on the scaffold accelerated wound healing. CONCLUSION: These findings suggest that the designed scaffold can be useful for skin regeneration applications.

Ginger's Antiapoptotic and Antioxidant Effects on Ovaries of Cyclophosphamide-therapied Rats.

BACKGROUND: In the recent decade, there has been increasing interest in preventing ovarian toxicity after chemotherapy exposure. It has been documented that ginger (Zingiber officinale) might normalize the hormonal balance and control the menstrual cycle.. OBJECTIVE: This study has analyzed whether ginger extract protects against cyclophosphamide (CP)-induced ovarian failure in rats. METHODS: Rats were distributed into four groups consisting of vehicle, CP, ginger, and CP + ginger. At the end of the treatment, all rats were killed under anesthesia to obtain ovarian tissues and blood samples for histological, molecular, and biochemical experiments. RESULTS: Our results indicated that ginger improves CP-caused histological changes in ovarian tissues and significantly restores serum hormonal abnormalities. Ginger also showed unique antioxidant, anti-inflammatory, and antiapoptotic properties in the ovarian tissues of CP-induced rats. Further, our findings indicated that ginger might activate the Nrf2 and SIRT and inhibit the PI3K/AKT pathway in the ovaries of CP-treated rats. In conclusion, ginger was found to protect against CP-caused ovarian toxicity in rats. CONCLUSION: The protective impacts of ginger may mediate, at least partly, by alleviating the oxidant state, inhibiting pro-inflammatory conditions, and exhibiting antiapoptotic activities.

Surface plasmon resonance-based oligonucleotide biosensor for Salmonella Typhi detection.

Due to high mortality rates, typhoid fever still is one of the major health problems in the world, particularly in developing countries. The lack of highly specific and sensitive diagnostic tests and the great resemblance of typhoid fever symptoms to other diseases made the false-negative diagnosis a major challenge in typhoid fever management. Hence, we decided to design a Surface Plasmon Resonance (SPR) based biosensor for specific detection of Salmonella typhi through DNA hybridization. The results showed that the 10 nM of the synthetic target sequence, as well as 1 nM of PCR product, were the lowest feasible detected concentrations by the designed biosensor. This genosensor was also found to significantly distinguish the complementary sequence with the accuracy of one base mismatch sequence. The surface of the chip can be regenerated with NaOH solution and used for consecutive diagnosis. Therefore, the function of the designed biosensor indicates its high potential for Salmonella typhi detection practice.

Nanomedicine innovations in spinal cord injury management: Bridging the gap.

Spinal cord injury (SCI) has devastating effects on a person's physical, social, and professional well-being. It is a life-altering neurological condition that significantly impacts individuals and their caregivers on a socioeconomic level. Recent advancements in medical therapy have greatly improved the diagnosis, stability, survival rates, and overall well-being of SCI patients. However, there are still limited options available for enhancing neurological outcomes in these patients. The complex pathophysiology of SCI, along with the numerous biochemical and physiological changes that occur in the damaged spinal cord, contribute to this gradual improvement. Currently, there are no therapies that offer the possibility of recovery for SCI, although several therapeutic approaches are being developed. However, these therapies are still in the early stages and have not yet demonstrated effectiveness in repairing the damaged fibers, which hinders cellular regeneration and the full restoration of motor and sensory functions. Considering the importance of nanotechnology and tissue engineering in treating neural tissue injuries, this review focuses on the latest advancements in nanotechnology for SCI therapy and tissue healing. It examines research articles from the PubMed database that specifically address SCI in the field of tissue engineering, with an emphasis on nanotechnology as a therapeutic approach. The review evaluates the biomaterials used for treating this condition and the techniques employed to create nanostructured biomaterials.

MicroRNA-425: A Pivotal Regulator Participating in Tumorigenesis of Human Cancers.

MicroRNAs (miRNAs) are small single-stranded regulatory RNAs that are shown to be dysregulated in a wide array of human cancers. MiRNAs play critical roles in cancer progression and function as either oncogenes or tumor suppressors through modulating various target genes. Therefore, they possess great potential as diagnostic and therapeutic targets for cancer detection and treatment. In particular, recent studies have illustrated that miR-425 is also dysregulated in various human malignancies and plays a fundamental role in cancer initiation and progression. miR-425 has been reported to function as a dual-role miRNA participating in the regulation of cellular processes, including metastasis, invasion, and cell proliferation by modulating multiple signaling pathways, such as TGF-ß, Wnt, and P13K/AKT pathways. Therefore, regarding recent researches showing the high therapeutic potential of miR-425, in this review, we have noted the impact of its dysregulation on signaling pathways and various aspects of tumorigenesis in a variety of human cancers.

Using chitosan-stabilized, hyaluronic acid-modified selenium nanoparticles to deliver CD44-targeted PLK1 siRNAs for treating bladder cancer.

Aims: Achieving an effective biocompatible system for siRNAs delivery to the tumor site remains a significant challenge. Materials & methods: Selenium nanoparticles (SeNPs) modified by chitosan (CS) and hyaluronic acid (HA) were fabricated for PLK1 siRNAs (siPLK1) delivery to the bladder cancer cells. The HA-CS-SeNP@siPLK1 efficacy was evaluated using in vitro and in vivo models. Results: HA-CS-SeNP@siPLK1 was selectively internalized into T24 cells through clathrin-mediated endocytosis. Treatment with HA-CS-SeNP@siPLK1 successfully silenced the PLK1 gene, inhibited cell proliferation and induced cell cycle arrest in vitro. HA-CS-SeNP@siPLK1 could also inhibit tumor growth in vivo without causing systemic toxicity. Conclusion: Our results suggest that HA-CS-SeNPs may provide a good vehicle for delivering siPLK1 to the bladder tumor site.

siRNAs are small biomolecules shown as novel insights in cancer gene therapy because of their capability to silence target genes. However, achieving an effective biocompatible system for siRNA delivery to the tumor site remains a significant challenge. This work aimed to develop a nanoparticle-based delivery system consisting of selenium nanoparticles modified by chitosan and hyaluronic acid to sustain the release of siRNAs to bladder cancer cells. The results of this study demonstrated that this nanosystem successfully silenced the PLK1 gene and reduced the proliferation in vitro and in vivo. These findings suggest that hyaluronic acid-chitosan-selenium nanoparticles may open a new insight for targeted gene therapy for bladder cancer.

Domino protocol for the synthesis of diversely functionalized derivatives of a novel fused pentacyclic antioxidant/anticancer fluorescent scaffold: Pyrazolo[5'',1'':2',3']pyrimido[4',5':5,6][1,4]thiazino[2,3-b]quinoxaline.

Rising to the challenge of formidable multi-step reaction needed for the synthesis of polycyclic compounds, an efficient one-pot two-step procedure for the synthesis of densely functionalized novel pyrazolo[5″,1'':2',3']pyrimido[4',5':5,6] [1,4]thiazino[2,3-b]quinoxalines from synthetically accessible starting materials 6-bromo-7-chloro-3-cyano-2-(ethylthio)-5-methylpyrazolo[1,5-a]pyrimidine, 3-aminoquinoxaline-2-thiol and some readily accessible alkyl halides was established. The domino reaction pathway involves cyclocondensation/N-alkylation sequence in K2CO3/N,N-dimethyl formamide under heating condition. DPPH free radical scavenging activity of all synthesized pyrazolo[5″,1'':2',3']pyrimido[4',5':5,6][1,4]thiazino[2,3-b]quinoxalines was evaluated to determine their antioxidant potentials. IC50 values were recorded in the range of 29-71 µM. N-benzyl substituted derivative represented the most effective antioxidant activity as well as antiproliferative activity against MCF-7 cells. Moreover, fluorescence in solution for these compounds exhibited strong red emission in the visible region (λflu. = 536-558 nm) with good to excellent quantum yields (61-95%). Due to their interesting fluorescence properties, these novel pentacyclic fluorophores can be used as fluorescent markers and probes for studies in biochemistry and pharmacology.

A critical review of the recent concept of artificial mechanical uterus design in relation to the maternal microbiome: An Update to past researches.

The microbiome in the female reproductive tract plays an essential role in immune modulation and reproductive health. However, various microbes become established during pregnancy, the balance of which plays a crucial role in embryonic development and healthy births. The contribution of disturbances in the microbiome profile to embryo health is poorly understood. A better understanding of the relationship between reproductive outcomes and the vaginal microbiota is needed to optimize the chances of healthy births. In this regards, microbiome dysbiosis refers to conditions in which the pathways of communication and balance within the normal microbiome are imbalanced due to the intrusion of pathogenic microorganisms into the reproductive system. This review summarizes the current state of knowledge on the natural human microbiome, with a focus on the natural uterine microbiome, mother-to-child transmission, dysbiosis, and the pattern of microbial change in pregnancy and parturition, and reviews the effects of artificial uterus probiotics during pregnancy. These effects can be studied in the sterile environment of an artificial uterus, and microbes with potential probiotic activity can be studied as a possible therapeutic approach. The artificial uterus is a technological device or biobag used as an incubator, allowing extracorporeal pregnancy. Establishing beneficial microbial communities within the artificial womb using probiotic species could modulate the immune system of both the fetus and the mother. The artificial womb could be used to select the best strains of probiotic species to fight infection with specific pathogens. Questions about the interactions and stability of the most appropriate probiotics, as well as dosage and duration of treatment, need to be answered before probiotics can be a clinical treatment in human pregnancy.

In-vitro and in-vivo evaluation of sustained-release buprenorphine using in-situ forming lipid-liquid crystal gels.

AIMS: Sustained-release systems reduce the incidence of drug side effects and the need for frequent drug consumption, thus increasing patient compliance with treatment. In this study, we aimed to produce sustained-release buprenorphine (BP) using lipid-liquid crystal gels. MAIN METHODS: The three experimental groups in this study included: group I: lipid-liquid crystal formulation 5 (F5) containing BP, group II: BP-free F5, group III: BP solution in NMP, and group IV: control (no treatment). The formulations were injected subcutaneously into the rabbits' back neck. KEY FINDINGS: The results showed that the time required to reach the drug's maximum concentration (Tmax) was longer in group I than in group III. The maximum BP concentration (Cmax) and the constants of the drug removal rate and drug absorption rate (Ka) were significantly higher in group III compared to group I. The half-life (t1/2) of the drug in blood circulation was significantly longer in group I than in group III. Histopathological analysis revealed no histological abnormalities in the skin and heart in group I (BP-containing F5); however, mild hyperemia was observed in interstitial vessels in group III (BP-containing NMP). The kidney and liver tissues showed normal structure in the control group, as well as groups I and II. However, in the group receiving BP-containing NMP, significant congestion, tissue damage, necrosis, and fibrosis were observed in the kidney and liver. SIGNIFICANCE: The results showed that the lipid-liquid crystal system can be used to design slow-release platforms for BP, minimizing the side effects associated with the use of its conventional forms.

Preparation of porous PCL-PEG-PCL scaffolds using supercritical carbon dioxide.

In this study, the Supercritical Carbon Dioxide (scCO2) gas foaming procedure was used in the preparation of scaffolds containing the model drug dexamethasone (DXMT). The method used did not include an organic solvent thus making it a safe method. The ring-opening polymerization of PCL-PEG-PCL (PCEC) triblock was conducted using an organocatalyst [1,8 diazabicyclo [5.4.0] undec-7-ene (DBU)]. After mixing 5.0 g of DXMT with 50.0 g of PCEC, hydraulic pressure was applied to compress the mixed powder into disc-like tablets. The tablet-like scaffold of the triblock containing DXMT was inserted into a scCO2 gas-foaming device. The peak porosity percentage of the synthesized triblock was found to be 55.58 %. Pressure, temperature, soaking time and the time required to depressurize were recorded as 198 bar, 50 °C, 2.0 h, and 28 min respectively. After treatment with scCO2, the scaffolds experienced an almost full release of DXMT in vitro after 30 days (83.74 ± 1.54 % vs 52.24 ± 2.03 % before scCO2 treatment). In conclusion, the results proved that the scCO2 gas foaming procedure could be employed for constructing modifiable PCEC scaffolds with plausible porosity and structural and morphological features which can manipulate drug release.

Targeted delivery of 5-fluorouracil, miR-532-3p, and si-KRAS to the colorectal tumor using layer-by-layer liposomes.

Co-delivery of siRNA or miRNA with chemotherapeutic drugs into tumor sites is an attractive synergetic strategy for treating colorectal cancer (CRC) due to their complementary mechanisms. In the current work, a liposome nanoparticle (Huang et al., Cancer Metastasis Rev., 2018, 37, 173-187) coated by cationic chitosan (CS) using a controlled layer-by-layer (LbL) process was designed to deliver simultaneous si-KRAS, miRNA-532-3p, and 5-Fluorouracil (5-FU) into CRC cells. The LbL NPs exhibited a spherical structure with an average size of 165.9 nm and effectively protected si-KRAS and miRNA-532-3p against degradation by serum and nucleases. Interestingly, the LbL NPs were successfully entered into cells and efficiently promoted cytotoxicity and suppressed cancer cell migration and invasion. In vivo, the LbL NPs reduced tumor growth in SW480-tumor-bearing mice models. In conclusion, these results suggested that the LbL NPs co-loaded with 5-FU and miR-532-3p/si-KRAS might provide a promising potential strategy for inhibiting the malignant phenotypes of CRC cells.

Conductive and Semiconductive Nanocomposite-Based Hydrogels for Cardiac Tissue Engineering.

Cardiovascular disease is the leading cause of death worldwide and the most common cause is myocardial infarction. Therefore, appropriate approaches should be used to repair damaged heart tissue. Recently, cardiac tissue engineering approaches have been extensively studied. Since the creation of the nature of cardiovascular tissue engineering, many advances have been made in cellular and scaffolding technologies. Due to the hydrated and porous structures of the hydrogel, they are used as a support matrix to deliver cells to the infarct tissue. In heart tissue regeneration, bioactive and biodegradable hydrogels are required by simulating native tissue microenvironments to support myocardial wall stress in addition to preserving cells. Recently, the use of nanostructured hydrogels has increased the use of nanocomposite hydrogels and has revolutionized the field of cardiac tissue engineering. Therefore, to overcome the limitation of the use of hydrogels due to their mechanical fragility, various nanoparticles of polymers, metal, and carbon are used in tissue engineering and create a new opportunity to provide hydrogels with excellent properties. Here, the types of synthetic and natural polymer hydrogels, nanocarbon-based hydrogels, and other nanoparticle-based materials used for cardiac tissue engineering with emphasis on conductive nanostructured hydrogels are briefly introduced.

Recent advances in nanoparticle-based photothermal therapy for breast cancer.

Breast cancer is one of the most common cancers among women that is associated with high mortality. Conventional treatments including surgery, radiotherapy, and chemotherapy, which are not effective enough and have disadvantages such as toxicity and damage to healthy cells. Photothermal therapy (PTT) of cancer cells has been took great attention by researchers in recent years due to the use of light radiation and heat generation at the tumor site, which thermal ablation is considered a minimally invasive method for the treatment of breast cancer. Nanotechnology has opened up a new perspective in the treatment of breast cancer using PTT method. Through NIR light absorption, researchers applied various nanostructures because of their specific nature of penetrating and targeting tumor tissue, increasing the effectiveness of PTT, and combining it with other treatments. If PTT is used with common cancer treatments, it can dramatically increase the effectiveness of treatment and reduce the side effects of other methods. PTT performance can also be improved by hybridizing at least two different nanomaterials. Nanoparticles that intensely absorb light and increase the efficiency of converting light into heat can specifically kill tumors through hyperthermia of cancer cells. One of the main reasons that have increased the efficiency of nanoparticles in PTT is their permeability and durability effect and they can accumulate in tumor tissue. Targeted PTT can be provided by incorporating specific ligands to target receptors expressed on the surface of cancer cells on nanoparticles. These nanoparticles can specifically target cancer cells by maintaining the surface area and increasing penetration. In this study, we briefly introduce the performance of light therapy, application of metal nanoparticles, polymer nanoparticles, carbon nanoparticles, and hybrid nanoparticles for use in PTT of breast cancer.

Recent advances in development of nano-carriers for immunogene therapy in various complex disorders.

Immunotherapy is a novel preference for the treatment of various complex diseases. Considering the application of varying agents for suppression or activation of the immune system, immunogene therapy was confirmed to stand as a proper alternative for other immunotherapeutic strategies due to its capability in targeting cells with more specificity that leads to controlling the expression of therapeutic genes. This method facilitates the local and single-dose application of most gene therapies that result in the usage of high therapeutic doses with a low risk of systemic side effects while being cost-efficient in long-term administrations. However, the existing barriers between the administration site and cell nucleus limited the clinical uses of genetic materials. These challenges can be overcome through the promising method of exerting non-carriers with high stability, low toxicity/immunogenicity, and simple modifications. In this study, we attempted to review the potential of nanoparticle application throughout the immunogene therapy of different diseases including cancer, microbial diseases, allergies, inflammatory bowel disease, rheumatoid arthritis, and respiratory infections. We included the outline of some challenges and opportunities in regards to the delivery of genetic materials that are based on nano-systems through immunotherapy of these disorders. Next to the promising future of these vectors, more detailed analyses are required to overcome the current limitations in clinical approaches.

Preparation and in vitro evaluation of injectable formulations of levothyroxine sodium using in situ forming hydrogel temperature-responsive systems based on PLA-PEG-PLA and PLGA-PEG-PLGA triblock copolymers.

Objectives: Recently, great attention has been paid to developing new drug delivery systems to manage the rate, time, and site of drug release. We aimed to design a novel drug delivery system to support targeted and gradual delivery of levothyroxine sodium. Materials and Methods: The triblock copolymers of PLA-PEG-PLA and PLGA-PEG-PLGA were constructed using the ring-opening copolymerization method and then purified and characterized by 1H-NMR, DSC, and GPC techniques. The phase transition temperature of the polymers was determined, and levothyroxine sodium stability was investigated in a phosphate-based buffer (pH 7.4). In vitro drug release into the PBS was measured at different concentrations of the triblocks for one month. Results: The results of NMR and GPC showed successful fabrication of the copolymers with low molecular weight dispersion and Tg points of -8.19 °C and -5.19 °C for PLA-PEG-PLA and PLGA-PEG-PLGA, respectively. Stability tests showed that during one month, most of the triblocks' masses degraded at 37 °C while levothyroxine sodium remained stable. Initial burst release of the drug in both copolymers is inversely correlated with the concentration of the polymer. Evaluation of drug release for 35 days showed that PLA-PEG-PLA had a slower drug release rate than PLGA-PEG-PLGA. Conclusion: Considering the low initial burst release, as well as continuous and long-term release kinetics of PLA-PEG-PLA and PLGA-PEG-PLGA copolymers, they can be used to gradually deliver levothyroxine sodium, obviating the need for frequent administrations and concerns over drug-food interactions.