Nanomedicine as potential cancer therapy via targeting dysregulated transcription factors.

Cancer as a disease possess quite complicated pathophysiological implications and is among the prominent causes of morbidity and mortality on global scales. Anti-cancer chemotherapy, surgery, and radiation therapy are some of the present-day conventional treatment options. However, these therapeutic paradigms own several retreats, including lack of specificity, non-targeted toxicological implications, inefficient drug delivery to targeted cells, and emergence of cancer resistance, ultimately causing ineffective cancer management. Owing to the advanced and better biophysical characteristic features and potentiality for the tailoring and customizations and in several fashions, nanotechnology can entirely transubstantiate the cancer identification and its managements. Additionally, nanotechnology also renders several answers to present-day mainstream limitations springing-up in anti-cancer therapeutics. Nanocarriers, owing to their outstanding physicochemical features including but not limited to their particle size, surface morphological features viz. shape etc., have been employed in nanomedicinal platforms for targeting various transcription factors leading to worthy pharmacological outcomes. This transcription targeting activates the wide array of cellular and molecular events like antioxidant enzyme-induction, apoptotic cell death, cell-cycle arrest etc. These outcomes are obtained after the activation or inactivation of several transcription factors and cellular pathways. Further, nanoformulations have been precisely calibrated and functionalized with peculiar targeting groups for improving their efficiency to deliver the drug-payload to specified and targeted cancerous cells and tissues. This review undertakes an extensive, across-the-board and all-inclusive approach consisting of various studies encompassing different types of tailored and customized nanoformulations and nanomaterials designed for targeting the transcription factors implicated in the process of carcinogenesis, tumor-maturation, growth and metastasis. Various transcription factors viz. nuclear factor kappa (NF-κB), signal transducer and activators of transcription (STAT), Cmyc and Twist-related protein 1 (TWIST1) along with several types of nanoparticles targeting these transcription factors have been summarized here. A section has also been dedicated to the different types of nanoparticles targeting the hypoxia inducing factors. Efforts have been made to summarize several other transcription factors implicated in various stages of cancer development, growth, progression and invasion, and their targeting with different kinds of nanomedicinal agents.

Future Nanotechnology-Based Strategies for Improved Management of Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) is a recalcitrant pathogen, which can cause gastric disorders. During the past decades, polypharmacy-based regimens, such as triple and quadruple therapies have been widely used against H. pylori. However, polyantibiotic therapies can disturb the host gastric/gut microbiota and lead to antibiotic resistance. Thus, simpler but more effective approaches should be developed. Here, some recent advances in nanostructured drug delivery systems to treat H. pylori infection are summarized. Also, for the first time, a drug release paradigm is proposed to prevent H. pylori antibiotic resistance along with an IVIVC model in order to connect the drug release profile with a reduction in bacterial colony counts. Then, local delivery systems including mucoadhesive, mucopenetrating, and cytoadhesive nanobiomaterials are discussed in the battle against H. pylori infection. Afterward, engineered delivery platforms including polymer-coated nanoemulsions and polymer-coated nanoliposomes are poposed. These bioinspired platforms can contain an antimicrobial agent enclosed within smart multifunctional nanoformulations. These bioplatforms can prevent the development of antibiotic resistance, as well as specifically killing H. pylori with no or only slight negative effects on the host gastrointestinal microbiota. Finally, the essential checkpoints that should be passed to confirm the potential effectiveness of anti-H. pylori nanosystems are discussed.

Self-assembled micelles loaded with itraconazole as anti-Acanthamoeba nano-formulation.

Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.

Protein coupled thionine acetate probed silica nanoparticles: An integrated laser-assisted therapeutic approach for treating cancer.

Herein, we report a multifaceted nanoformulation, developed by binding thionine acetate (TA) in silica matrix to form TA loaded silica nanoparticles (STA Nps), which were characterized using various physicochemical techniques. STA NPs were spherical shaped having size 40-50 nm and exhibited good heating efficiency, improved photostability and singlet oxygen production rate than TA alone. In PDT experiment, the rate of degradation for ABDMA was enhanced from 0.1367 min-1 for TA alone to 0.1774 min-1 for STA Nps, depicting an increase in the reactive oxygen species (ROS) generation ability of STA Nps. Further, the cytotoxicity of STA Nps was investigated by carrying out the biophysical studies with Calf thymus DNA (Ct-DNA) and Human Serum Albumin (HSA). The results indicated that the binding of STA Nps to Ct-DNA causes alterations in the double helix structure of DNA and as a result, STA Nps can impart chemotherapeutic effects via targeting DNA. STA Nps showed good binding affinity with HSA without compromising the structure of HSA, which is important for STA Nps sustainable biodistribution and pharmacokinetics. Based on this study, it is suggested that because of the synergistic effect of chemo and phototherapy, STA Nps can be extensively utilized as potential candidates for treating cancer.

Multidrug-resistant Bacillus species isolated from hospital soil environment is controlled by nanobiotics incorporated nanoformulation.

Multidrug resistance is a serious hazard to the environment, it claims a large number of lives every year. Lack of drug options and easy transmission of these organisms remain the biggest threat in treating the relative infections whose causative systems have evolved and become stronger in due course of time. Hospitals serve as one of the largest breeding grounds for harbouring these organisms. This study aims to isolate and characterize multidrug-resistant microorganisms from soil samples collected from hospital waste dumping premises. Polyherbal nanoformulation was synthesized from ethno-medicinal source Triphala (three berries) and characterized using various physico-chemical characterization techniques. The antibacterial efficacy of the polyherbal nanoformulation was evaluated by employing various assays to determine MIC, MBC, and biofilm inhibition potential in isolated strains. Bacterial colonies were isolated and the DNA was sequenced. The isolated organisms were identified as Bacillus cereus, Bacillus licheniformis, and Bacillus pumilus and they were subjected to antibiotic susceptibility by using various antibiotics. It was found that all the microorganisms were multidrug-resistant and possessed resistance to various classes of antibiotics. The various antibacterial assays showed that the polyherbal nanoformulation was highly effective in controlling growth and biofilm formation even at lower concentrations when compared with commercial antibiotics. The novelty of this research work lies in combining the beneficial effects of silver and polyherbal drugs into a single Polyherbal nanoformulation. This is the first novel report to utilize polyherbal nanoformulation to control the multidrug-resistant microorganisms thriving in hospital waste dumping sites. Hence, this nanobiotics incorporated polyherbal nanoformulation can be developed into a commercial product to treat the hospital waste material before dumping it into the environment.

Testing of acute and sub-acute toxicity profile of novel naproxen sodium nanoformulation in male and female mice.

Nanodrugs offer promising alternatives to conventionally used over the counter drugs. Compared to its free form, therapeutic benefits, and gastric tissue safety of naproxen sodium nanoformulation (NpNF) were recently demonstrated. Essential regulatory safety data for this formulation are, however, not available. To address this, male and female BALB/c mice were subjected to acute and 14-day repeated-oral dose assessments. Our data indicate that NpNF was well tolerated up to 2000 mg/kg b.w. A 14-day subacute toxicity testing revealed that the oral administration of low dose (30 mg/kg) NpNF did not produce any adverse effects on blood profile and serum biochemical parameters. Levels of oxidative stress markers and antioxidant enzymes neared normal. Histology of selected tissues also showed no evidence of toxicity. In contrast, a ten-fold increase in NpNF dosage (300 mg/kg), demonstrated, irrespective of gender, mild to moderate toxicity (p < 0.05) in the brain, stomach, and heart tissues, while ROS, LPO, CAT, SOD, POD, and GSH levels remained unaffected in the liver, kidney, spleen, testis, and seminal vesicles. No effect on serum biochemical parameters, overall indicated a no-observed-adverse-effect level (NOAEL) is 300 mg/kg. Further increase in dosage (1000 mg/kg) significantly altered all parameters demonstrating that high dose is toxic.

Fisetin-loaded chitosan nanoparticles ameliorate pilocarpine-induced temporal lobe epilepsy and associated neurobehavioral alterations in mice: Role of ROS/TNF-α-NLRP3 inflammasomes pathway.

Fisetin has displayed potential as an anticonvulsant in preclinical studies yet lacks clinical validation. Challenges like low solubility and rapid metabolism may limit its efficacy. This study explores fisetin-loaded chitosan nanoparticles (NP) to address these issues. Using a murine model of pilocarpine-induced temporal lobe epilepsy, we evaluated the anticonvulsant and neuroprotective effects of fisetin NP. Pilocarpine-induced seizures and associated neurobehavioral deficits were assessed after administering subtherapeutic doses of free fisetin and fisetin NP. Changes in ROS, inflammatory cytokines, and NLRP3/IL-18 expression in different brain regions were estimated. The results demonstrate that the fisetin NP exerts protection against seizures and associated depression-like behavior and memory impairment. Furthermore, biochemical, and histological examinations supported behavioral findings suggesting attenuation of ROS/TNF-α-NLRP3 inflammasome pathway as a neuroprotective mechanism of fisetin NP. These findings highlight the improved pharmacodynamics of fisetin using fisetin NP against epilepsy, suggesting a promising therapeutic approach against epilepsy and associated behavioral deficits.

Essential oils and their nanoformulations for breast cancer therapy.

Breast Cancer (BC) is the most prevalent type of cancer in the world. Current treatments include surgery, radiation, and chemotherapy but often are associated with high toxicity to normal tissues, chemoresistance, and relapse. Thus, developing novel therapies which could combat these limitations is essential for effective treatment. In this context, phytochemicals are increasingly getting popular due to their safety profile, ability to efficiently target tumors, and circumvent limitations of existing treatments. Essential Oils (EOs) are mixtures of various phytochemicals which have shown potential anticancer activity in preclinical BC models. However, their clinical translation is limited by factors such as high volatility, low stability, and poor solubility. Nanotechnology has facilitated their encapsulation in a variety of nanostructures and proven to overcome these limitations. In this review, we have efficiently summarized the current knowledge on the anticancer effect of EOs and constituents in both in in vitro and in in vivo BC models. Further, we also provide a descriptive account on the potential of nanotechnology in enhancing the anti-BC activity of EOs and their constituents. The papers discussed in this review were selected using the keywords "antiproliferative Essential Oils in breast cancer," "anticancer activity of Essential Oil in breast cancer," and "cytotoxicity of Essential Oils in breast cancer" performed in PubMed and ScienceDirect databases.

Comprehensive exploration of Biochanin A as an oncotherapeutics potential in the treatment of multivarious cancers with molecular insights.

Cancer is considered a leading cause of mortality. This rising cancer death rate and several existing limitations like side effects, poor efficacies, and high cost of the present chemotherapeutic agents have increased the demand for more potent and alternative cancer treatments. This review elucidated a brief overview of Biochanin A (BCA) and its potentiality on various cancers with details of anticancer mechanism. According to our review, a number of studies including in silico, in vitro, pre-clinical, and clinical trials have tested to evaluate the efficacy of BCA. This compound is effective against 15 types of cancer, including breast, cervical, colorectal, gastric, glioblastoma, liver, lung, melanoma, oral, osteosarcoma, ovarian, pancreatic, pharynx, prostate, and umbilical vein cancer. The general anticancer activities of this compound are mediated via several molecular processes, including regulation of apoptosis, cell proliferation, metastasis and angiogenesis, signaling, enzymatic pathways, and other mechanisms. Targeting both therapeutic and oncogenic proteins, as well as different pathways, makes up the molecular mechanism underlying the anticancer action. Many signaling networks and their components, such as EFGR, PI3K/Akt/mTOR, MAPK, MMP-2, MMP-9, PARP, Caspase-3/8/9, Bax, Bcl2, PDL-1, NF-κB, TNF-α, IL-6, JAK, STAT3, VEGFR, VEGF, c-MY, Cyclin B1, D1, E1 and CDKs, Snail, and E-cadherin proteins, can be regulated in cancer cells by BCA. Such kind of anticancer properties of BCA could be a result of its correct structural chemistry. The use of BCA-based therapies as nano-carriers for the delivery of chemotherapeutic medicines has the potential to be very effective. This natural compound synergises with other natural compounds and standard drugs, including sorafenib, 5-fluorouracil, temozolomide, doxorubicin, apigenin, and genistein. Moreover, proper use of this compound can reverse multidrug resistance through numerous mechanisms. BCA has better drug-likeness and pharmacokinetic properties and is nontoxic (eye, liver, kidney, skin, cardio) in human bodies. As having a wide range of cancer-fighting mechanisms, synergistic effects, and good pharmacokinetic properties, BCA can be used as a supplementary food until standard drugs are available at pharma markets.

Influence of nano-formulations of clove bud (Syzygium aromaticum) extract on freezing ability, antioxidant capacity, caspase-3 activity, acrosome reaction and fertility of frozen rabbit semen.

The current study aimed to investigate the impact of nano-formulations of clove bud ethanolic extract (CBENF) in the extender on sperm characteristics, antioxidant capacity, oxidative biomarkers, enzymatic activity, apoptosis and fertility of post-thawed rabbit semen. Twelve mature male rabbits semen samples were pooled and cryopreserved in a Tris-egg yolk-based extender containing varying concentrations of CBENF (0, 25, 50, 75 and 100 µg/mL). After the equilibration and freezing-thawing process, CBENF (100 µg /mL) significantly enhanced progressive motility, viability and membrane integrity. Conversely, sperm abnormality was significantly reduced by CBENF supplementation. Total antioxidant capacity was increased in the post-thawed sperm medium, while nitric oxide and malondialdehyde were decreased in all CBENF concentrations. The lactic dehydrogenase and caspase-3 activities were decreased, whereas the number of live spermatozoa with an intact acrosome was increased in all CBENF concentrations. Conception rate and litter size per doe were higher in doe rabbits inseminated with semen supplemented with 100 µg CBENF/mL than un-supplemented group (76% vs. 52% and 8.4 vs. 7.7/doe), with no statistical differences. These findings suggest that supplementing rabbit extenders with 100 µg of CBENF/mL could be an effective strategy for enhancing freeze-thawing rabbit sperm attributes and fertility.

Unveiling the Role of Nano-Formulated Red Algae Extract in Cancer Management.

Cancer is one of the major causes of death, and its negative impact continues to rise globally. Chemotherapy, which is the most common therapy, has several limitations due to its tremendous side effects. Therefore, developing an alternate therapeutic agent with high biocompatibility is indeed needed. The anti-oxidative effects and bioactivities of several different crude extracts of marine algae have been evaluated both in vitro and in vivo. In the present study, we synthesized the aqueous extract (HA) from the marine algae Amphiroa anceps, and then, a liposome was formulated for that extract (NHA). The extracts were characterized using different photophysical tools like dynamic light scattering, UV-visible spectroscopy, FTIR, scanning electron microscopy, and GC-MS analysis. The SEM image revealed a size range of 112-185 nm for NHA and the GC-MS results showed the presence of octadecanoic acid and n-Hexadecanoic acid in the majority. The anticancer activity was studied using A549 cells, and the NHA inhibited the cancer cells dose-dependently, with the highest killing of 92% at 100 µg/mL. The in vivo studies in the zebrafish model showed that neither the HA nor NHA of Amphiroa anceps showed any teratogenic effect. The outcome of our study showed that NHA can be a potential drug candidate for inhibiting cancer with good biocompatibility up to a dose of 100 µg/mL.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

Pharmacokinetics and Histotoxic Profile of a Novel Azithromycin-Loaded Lipid-Based Nanoformulation.

Azithromycin traditional formulations possesses poor oral bioavailability which necessitates development of new formulation with enhanced bioavailability of the drug. The objective of current research was to explore the kinetics and safety profile of the newly developed azithromycin lipid-based nanoformulation (AZM-NF). In the in-vitro study of kinetics profiling, azithromycin (AZM) release was assessed using dialysis membrane enclosing equal quantity of either AZM-NF, oral suspension of azithromycin commercial product (AZM-CP), or azithromycin pure drug (AZM-PD) in simulated intestinal fluid. The ex-vivo study was performed using rabbit intestinal segments in physiological salts solution in a tissue bath. The in-vivo study was investigated by oral administration of AZM to rabbits while taking blood samples at predetermined time-intervals, followed by HPLC analysis. The toxicity study was conducted in rats to observe histopathological changes in rat's internal organs. In the in-vitro study, maximum release was 95.38 ± 4.58% for AZM-NF, 72.79 ± 8.85% for AZM-CP, and 46.13 ± 8.19% for AZM-PD (p < 0.0001). The ex-vivo investigation revealed maximum permeation of 85.68 ± 5.87 for AZM-NF and 64.88 ± 5.87% for AZM-CP (p < 0.001). The in-vivo kinetics showed Cmax 0.738 ± 0.038, and 0.599 ± 0.082 µg/ml with Tmax of 4 and 2 h for AZM-NF and AZM-CP respectively (p < 0.01). Histopathological examination revealed compromised myocardial fibers integrity by AZM-CP only, liver and kidney showed mild aberrations by both formulations, with no remarkable changes in the rest of studied organs. The results showed that AZM-NF exhibited significantly enhanced bioavailability with comparative safer profile to AZM-CP investigated.

Advent of phytobiologics and nano-interventions for bone remodeling: a comprehensive review.

Bone metabolism constitutes the intricate processes of matrix deposition, mineralization, and resorption. Any imbalance in these processes leads to traumatic bone injuries and serious disease conditions. Therefore, bone remodeling plays a crucial role during the regeneration process maintaining the balance between osteoblastogenesis and osteoclastogenesis. Currently, numerous phytobiologics are emerging as the new therapeutics for the treatment of bone-related complications overcoming the synthetic drug-based side effects. They can either target osteoblasts, osteoclasts, or both through different mechanistic pathways for maintaining the bone remodeling process. Although phytobiologics have been widely used since tradition for the treatment of bone fractures recently, the research is accentuated toward the development of osteogenic phytobioactives, constituent-based drug designing models, and efficacious delivery of the phytobioactives. To achieve this, different plant extracts and successful isolation of their phytoconstituents are critical for osteogenic research. Hence, this review emphasizes the phytobioactives based research specifically enlisting the plants and their constituents used so far as bone therapeutics, their respective isolation procedures, and nanotechnological interventions in bone research. Also, the review enlists the vast array of folklore plants and the newly emerging nano-delivery systems in treating bone injuries as the future scope of research in the phytomedicinal orthopedic applications.

Enhancement of bioavailability and bioactivity of diet-derived flavonoids by application of nanotechnology: a review.

Flavonoids, which are a class of polyphenols widely existing in food and medicine, have enormous pharmacological effects. The functional properties of flavonoids are mainly distributed to their anti-oxidative, anticancer, and anti-inflammatoryeffects, etc. However, flavonoids' low bioavailability limits their clinical application, which is closely related to their intestinal absorption and metabolism. In addition, because of the short residence time of oral bioactive molecules in the stomach, low permeability and low solubility in the gastrointestinal tract, flavonoids are easy to be decomposed by the external environment and gastrointestinal tract after digestion. To tackle these obstacles, technological approaches like microencapsulation have been developed and applied for the formulation of flavonoid-enriched food products. In the light of these scientific advances, the objective of this review is to establish the structural requirements of flavonoids for appreciable anticancer, anti-inflammatory, and antioxidant effects, and elucidate a comprehensive mechanism that can explain their activity. Furthermore, the novelty in application of nanotechnology for the safe delivery of flavonoids in food matrices is discussed. After a literature on the flavonoids and their health attributes, the encapsulation methods and the coating materials are presented.

Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections.

With the rapid outbreak of respiratory viral infections, various biological (e.g. vaccines, peptides, recombinant proteins, antibodies and genes) and antiviral agents (e.g. ribavirin, palivizumab and valaciclovir) have been successfully developed for the treatment of respiratory virus infections such as influenza, respiratory syncytial virus and SARS-CoV-2 infections. These therapeutics are conventionally delivered via oral, intramuscular or injection route and are associated with several adverse events due to systemic toxicity. The inherent in vivo instability of biological therapeutics may hinder them from being administered without proper formulations. Therefore, we have witnessed a boom in nanotechnology coupled with a needle-free administration approach such as the inhalation route for the delivery of complex therapeutics to treat respiratory infections. This review discussed the recent advances in the inhalation strategies of nanoformulations that target virus respiratory infections.

An overview on nanoplatforms for statins delivery: Perspectives for safe and effective therapy.

Statins are the most widely used pharmacological agents for reducing blood cholesterol levels and treating atherosclerotic cardiovascular diseases. Most of the statins' derivatives have been limited by water solubility, bioavailability, and oral absorption, which has led to adverse effects on several organs, especially at high doses. As an approach to reducing statin intolerance, achieving a stable formulation with improved efficacy and bioavailability at low doses has been suggested. Nanotechnology-based formulations may provide a therapeutic benefit over traditional formulations in terms of potency and biosafety. Nanocarriers can provide tailored delivery platforms for statins, thereby enhancing the localized biological effects and lowering the risk of undesired side effects while boosting statin's therapeutic index. Furthermore, tailored nanoparticles can deliver the active cargo to the desired site, which culminates in reducing off-targeting and toxicity. Nanomedicine could also provide opportunities for therapeutic methods by personalized medicine. This review delves into the existing data on the potential improvement of statin therapy using nano-formulations.

In vitro antibacterial activity of green tea-loaded chitosan nanoparticles on caries-related microorganisms and dentin after Er:YAG laser caries removal.

This study aimed to determine the inhibitory effects of green tea (Gt), EGCG, and nanoformulations containing chitosan (Nchi) and chitosan+green tea (Nchi+Gt) against Streptococcus mutans and Lactobacillus casei. In addition, the antibacterial effect of nanoformulations was evaluated directly on dentin after the selective removal of carious lesion. At first, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against S. mutans and L. casei isolates were investigated. In parallel, dentin specimens were exposed to S. mutans to induce carious lesions. Soft dentin was selectively removed by Er:YAG laser (n=33) or bur (n=33). Remaining dentin was biomodified with Nchi (n=11) or Gt+Nchi (n=11). Control group (n=11) did not receive any treatment. Dentin scraps were collected at three time points. Microbiological analyses were conducted and evaluated by agar plate counts. Gt at 1:32 dilution inhibited S. mutans growth while 1:16 was efficient against L. casei. EGCG at 1:4 dilution completely inhibited S. mutans and L. casei growth. Independently of the association with Gt, Nchi completely inhibited S. mutans at 1:4 dilution. For L. casei, different concentrations of Nchi (1:32) and Nchi+Gt (1:8) were required to inhibit cell growth. After selective carious removal, viability of S. mutans decreased (p<0.001), without difference between bur and Er:YAG laser (p>0.05). Treatment with Nchi and Nchi+Gt did not influence the microbial load of S. mutans on dentin (p>0.05). Although variations in concentrations were noticed, all compounds showed antibacterial activity against S. mutans and L. casei. Both bur and Er:YAG laser have effectively removed soft dentin and reduced S. mutans counts. Nanoformulations did not promote any additional antibacterial effect in the remaining dentin.

Liver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications.

Hepatocytes exert pivotal roles in metabolism, protein synthesis and detoxification. Non-parenchymal liver cells (NPCs), largely comprising macrophages, dendritic cells, hepatic stellate cells and liver sinusoidal cells (LSECs), serve to induce immunological tolerance. Therefore, the liver is an important target for therapeutic approaches, in case of both (inflammatory) metabolic diseases and immunological disorders. This review aims to summarize current preclinical nanodrug-based approaches for the treatment of liver disorders. So far, nano-vaccines that aim to induce hepatitis virus-specific immune responses and nanoformulated adjuvants to overcome the default tolerogenic state of liver NPCs for the treatment of chronic hepatitis have been tested. Moreover, liver cancer may be treated using nanodrugs which specifically target and kill tumor cells. Alternatively, nanodrugs may target and reprogram or deplete immunosuppressive cells of the tumor microenvironment, such as tumor-associated macrophages. Here, combination therapies have been demonstrated to yield synergistic effects. In the case of autoimmune hepatitis and other inflammatory liver diseases, anti-inflammatory agents can be encapsulated into nanoparticles to dampen inflammatory processes specifically in the liver. Finally, the tolerance-promoting activity especially of LSECs has been exploited to induce antigen-specific tolerance for the treatment of allergic and autoimmune diseases.

Anti-arthritic effects of geranium essential oil loaded chitosan nanoparticles in Freund's complete adjuvant induced arthritic rats through down-regulation of inflammatory cytokines.

Geranium essential oil (GEO) has been widely used in aromatherapy and traditional medicines. Nanoencapsulation, a novel technique has emerged to overcome the environmental degradation and less oral bioavailability of essential oils. This work was undertaken to encapsulate geranium essential oil in chitosan nanoparticles (GEO-CNPs) by ionic gelation technique and to explore anti-arthritic and anti-inflammatory potential in FCA-induced arthritic model in rats. The GEO was characterized by gas chromatography flame ionization detector (GCFID) and the nanosuspension was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-rays diffraction (XRD). The Wistar albino rats (n = 32) were separated into four groups; Group 1 and 2 were considered as normal and arthritic controls. Group 3 was positive control that received oral celecoxib for 21 days while Group 4 was treated with oral GEO-CNPs after the induction of arthritis. Hind paw ankle joints diameters were weekly measured throughout the study and significant decrease (5.5 ± 0.5 mm) was observed in GEO-CNPs treatment group in comparison to arthritic group (9.17 ± 0.52 mm). Blood samples were drawn at end for evaluation of hematological, biochemical and inflammatory biomarkers. A significant upregulation of red blood cells and hemoglobin while downregulation of white blood cells, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and rheumatoid factor (RF) was observed. Ankles were transected for the histopathological and radiographic examination after animals were sacrificed which confirmed the alleviation of necrosis along cellular infiltration. It was concluded that GEO-CNPs were found to possess excellent therapeutic potential and promising candidates to reduce FCA-induced arthritis.