Emerging Trends of Nanomedicines in the Management of Prostate Cancer: Perspectives and Potential Applications.

Prostate cancer is one of the most life-threatening disorders that occur in males. It has now become the third most common disease all over the world, and emerging cases and spiking mortality rates are becoming more challenging day by day. Several approaches have been used to treat prostate cancer, including surgery, radiation therapy, chemotherapy, etc. These are painful and invasive ways of treatment. Primarily, chemotherapy has been associated with numerous drawbacks restricting its further application. The majority of prostate cancers have the potential to become castration-resistant. Prostate cancer cells exhibit resistance to chemotherapy, resistance to radiation, ADT (androgen-deprivation therapy) resistance, and immune stiffness as a result of activating tumor-promoting signaling pathways and developing resistance to various treatment modalities. Nanomedicines such as liposomes, nanoparticles, branched dendrimers, carbon nanotubes, and quantum dots are promising disease management techniques in this context. Nanomedicines can target the drugs to the target site and enhance the drug's action for a prolonged period. They may also increase the solubility and bioavailability of poorly soluble drugs. This review summarizes the current data on nanomedicines for the prevention and treatment of prostate cancer. Thus, nanomedicine is pioneering in disease management.

Multifunctional curcumin mediated zinc oxide nanoparticle enhancing biofilm inhibition and targeting apoptotic specific pathway in oral squamous carcinoma cells.

BACKGROUND: Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties. METHODS: In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity. RESULTS: ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40 µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10 µg/mL, 20 µg/mL, 40 µg/mL, and 80 µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells. CONCLUSIONS: This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.

In-situ gel: A smart carrier for drug delivery.

In-situ gel technology is a promising drug delivery strategy that undergoes a 'sol to gel' transition upon administration, providing controlled and prolonged drug release. These gels are composed of cross-linked 3D networks of polymers, with hydrogels being a specific type of absorbing water while retaining their shape. Gelation can be triggered by various stimuli, such as temperature, pH, ions, and light. They offer several advantages like improved patient compliance, extended drug residence time, localized drug delivery, etc, but also have some disadvantages like drug degradation and limited mechanical strength. In-situ gel falls into three categories: temperature-sensitive, ion-sensitive, and pH-sensitive, but multi-responsive gels that respond to multiple stimuli have better drug release characteristics. The mechanism of in-situ gel formation involves physical and chemical mechanisms. There are various applications of in-situ gel, like ocular drug delivery, nose-to-brain delivery, etc. In this review, we have discussed the types, and mechanisms of in-situ gel & use of in-situ gel in the treatment of different diseases through various routes like buccal, vaginal, ocular, nasal, etc., along with its use in targeted drug delivery.

Nanosponge: A promising and intriguing strategy in medical and pharmaceutical Science.

The complicated chemical reactions involved in the production of the newer drug delivery systems have mainly impeded efforts to build successful targeted drug delivery systems for a prolonged duration of time. Nanosponges, a recently created colloidal system, have the potential to overcome issues with medication toxicity, decreased bioavailability, and drug release over a wide area because they can be modified to work with both hydrophilic and hydrophobic types of drugs. Nanosponges are small sized with a three-dimensional network having a porous cavity. They can be prepared easily by crosslinking cyclodextrins with different compounds. Due to Cyclodextrin's outstanding biocompatibility, stability, and safety, a number of Cyclodextrin-based drug delivery systems have been developed promptly. The nanosponge drug delivery system possesses various applications in various ailments such as cancer, autoimmune diseases, theranostic applications, enhanced bioavailability, stability, etc. This review elaborates on benefits and drawbacks, preparation techniques, factors affecting their preparation, characterization techniques, applications, and most current developments in nanosponges.

Current Trends in Nanotechnology-based Drug Delivery Systems for the Diagnosis and Treatment of Malaria: A Review.

Malaria is still a major endemic disease transmitted in humans via Plasmodium-infected mosquitoes. The eradication of malarial parasites and the control measures have been rigorously and extensively deployed by local and international health organizations. Malaria's recurrence is a result of the failure to entirely eradicate it. The drawbacks related to malarial chemotherapy, non-specific targeting, multiple drug resistance, requirement of high doses, intolerable toxicity, indefinable complexity of Plasmodium's life cycle, and advent of drug-resistant strains of P. falciparum are the causes of the ineffective eradication measures. With the emergence of nanotechnology and its application in various industrial domains, the rising interest in the medical field, especially in epidemiology, has skyrocketed. The applications of nanosized carriers have sparked special attention, aiming towards minimizing the overall side effects caused due to drug therapy and avoiding bioavailability. The applications of concepts of nanobiotechnology to both vector control and patient therapy can also be one of the approaches. The current study focuses on the use of hybrid drugs as next-generation antimalarial drugs because they involve fewer drug adverse effects. The paper encompasses the numerous nanosized delivery-based systems that have been found to be effective among higher animal models, especially in treating malarial prophylaxis. This paper delivers a detailed review of diagnostic techniques, various nanotechnology approaches, the application of nanocarriers, and the underlying mechanisms for the management of malaria, thereby providing insights and the direction in which the current trends are imparted from the innovative and technological perspective.

A Glance on Nanovaccine: A Potential Approach for Disease Prevention.

There are several vaccines available for preventing various bacterial and viral infections, but still, there are many challenges that require the development of noninvasive, more efficient, and active vaccines. The advancement in biotechnological tools has provided safer antigens, such as nucleic acids, proteins etc., but due to their lower immunogenic property, adjuvants of stronger immune response are required. Nanovaccines are effective vaccines when compared with conventional vaccines as they can induce both Humoral and cell-mediated immune responses and also provide longer immunogenic memory. The nanocarriers used in vaccines act as adjuvant. They provide site-specific delivery of antigens and can be used in conjugation with immunostimulatory molecules for enhancing adjuvant therapy. The nanovaccines avoid degrading cell pathways and provide effective absorption into blood vessels. The higher potential of nanovaccines to treat various diseases, such as Acquired Immuno Deficiency Syndrome, Cancer, Tuberculosis, Malaria and many others, along with their immunological mechanisms and different types, have been discussed in the review.

A Comprehensive Review on Niosomes as a Tool for Advanced Drug Delivery.

Over the past few decades, advancements in nanocarrier-based therapeutic delivery have been significant, and niosomes research has recently received much interest. The self-assembled nonionic surfactant vesicles lead to the production of niosomes. The most recent nanocarriers, niosomes, are self-assembled vesicles made of nonionic surfactants with or without the proper quantities of cholesterol or other amphiphilic molecules. Because of their durability, low cost of components, large-scale production, simple maintenance, and high entrapment efficiency, niosomes are being used more frequently. Additionally, they enhance pharmacokinetics, reduce toxicity, enhance the solubility of poorly water-soluble compounds, & increase bioavailability. One of the most crucial features of niosomes is their controlled release and targeted diffusion, which is utilized for treating cancer, infectious diseases, and other problems. In this review article, we have covered all the fundamental information about niosomes, including preparation techniques, niosomes types, factors influencing their formation, niosomes evaluation, applications, and administration routes, along with recent developments.

A Snapshot of Current Updates and Future Prospects of 3D Printing in Medical and Pharmaceutical Science.

3D printing in other fields, such as aviation, is quite old, but in the pharmaceutical area, it is an emerging technique. 3D printing is used to formulate various drug delivery systems and dosage forms with complex geometry. It allows large and fast production of products according to the need of the patient. Today, it is the widely used manufacturing technique in the healthcare field for the engineering of tissues and tissue models, production of medicines and medical devices, organ and tissue bioprinting, implant manufacturing, and production of polypills, vaginal rings, orodispersible films, etc. It allows the production of various dosage forms with complex release profiles containing multiple active ingredients. It is used for manufacturing medicines according to the need of individual patients focusing on the concept of personalized medicines. The idea of customized medicines allows change of dosage and design of the product as per individual and with decreased side effects. This review details various techniques of 3D printing used, such as stereolithography, fused deposition modeling, inkjet printing, etc., and applications and dosage forms developed with the latest patents. The significant challenges in the emergence of the 3D printing technique are the involvement of complex combinations to achieve desired properties, and also, the bioprinter involved provides slow and less resolution. The materials prepared by this technique are both biocompatible and printable, due to which additive manufacturing is increasing in the field of medicine.

A highly stable terbium(III) metal-organic framework MOF-76(Tb) for hydrogen storage and humidity sensing.

The present study described the synthesis and characterization of MOF-76(Tb) for hydrogen storage and humidity sensing applications. The structure and morphology of as-synthesized material were studied using powder X-ray diffraction, scanning, and transmission electron microscopy. The crystal structure of MOF-76(Tb) consists of terbium(III) and benzene-1,3,5-tricarboxylate(-III) ions, one coordinated aqua ligand and one crystallization N,N´-dimethylformamide molecule. The polymeric framework of MOF-76(Tb) contains 1D sinusoidally shaped channels with sizes of 6.6 × 6.6 Å propagating along c crystallographic axis. The thermogravimetric analysis of the prepared material exhibited thermal stability up to 600 °C. At 77 K and pressure up to 20 bar; 0.6 wt.% hydrogen storage capacity for MOF-76(Tb) was observed. Finally, the humidity sensing measurements (water adsorption experiments) were performed, and the results indicate that MOF-76(Tb) is not a suitable material for moisture sensing applications.

Freeform 3D Ice Printing (3D-ICE) at the Micro Scale.

Water is one of the most important elements for life on earth. Water's rapid phase-change ability along with its environmental and biological compatibility also makes it a unique structural material for 3D printing of ice structures reproducibly and accurately. This work introduces the freeform 3D ice printing (3D-ICE) process for high-speed and reproducible fabrication of ice structures with micro-scale resolution. Drop-on-demand deposition of water onto a -35 °C platform rapidly transforms water into ice. The dimension and geometry of the structures are critically controlled by droplet ejection frequency modulation and stage motions. The freeform approach obviates layer-by-layer construction and support structures, even for overhang geometries. Complex and overhang geometries, branched hierarchical structures with smooth transitions, circular cross-sections, smooth surfaces, and micro-scale features (as small as 50 µm) are demonstrated. As a sample application, the ice templates are used as sacrificial geometries to produce resin parts with well-defined internal features. This approach could bring exciting opportunities for microfluidics, biomedical devices, soft electronics, and art.

Gd(III) metal-organic framework as an effective humidity sensor and its hydrogen adsorption properties.

Metal-organic frameworks (MOFs) represent a class of nanoporous materials built up by metal ions and organic linkers with several interesting potential applications. The present study described the synthesis and characterization of Gd(III)-based MOF with the chemical composition [Gd(BTC)(H2O)]·DMF (BTC - trimesate, DMF = N,N'-dimethylformamide), known as MOF-76(Gd) for hydrogen adsorption/desorption capacity and humidity sensing applications. The structure and morphology of as-synthesized material were studied using powder X-ray diffraction, scanning and transmission electron microscopy. The crystal structure of MOF-76(Gd) consists of gadolinium (III) and benzene-1,3,5-tricarboxylate ions, one coordinated aqua ligand and one crystallization DMF molecule. The polymeric framework of MOF-76(Gd) contains 1D sinusoidally shaped channels with sizes of 6.7 × 6.7 Å propagating along c crystallographic axis. The thermogravimetric analysis, heating infrared spectroscopy and in-situ heating powder X-ray diffraction experiments of the prepared framework exhibited thermal stability up to 550 °C. Nitrogen adsorption/desorption measurement at -196 °C showed a BET surface area of 605 m2 g-1 and pore volume of 0.24 cm3 g-1. The maximal hydrogen storage capacity of MOF-76(Gd) was 1.66 wt % and 1.34 wt % -196 °C and -186 °C and pressure up to 1 bar, respectively. Finally, the humidity sensing measurements (water adsorption experiments) were performed, and the results indicate that MOF-76(Gd) is a suitable material for moisture sensing application with a fast response (11 s) and recovery time (2 s) in the relative humidity range of 11-98%.

Hypercoagulopathy in COVID-19, Deep Venous Thrombosis After Extra-Corporeal Membrane Oxygenation Therapy: A Case Report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has caused a pandemic across the world in the years 2019 - 2020 with over 100 countries reporting high infection rates. The virus is unique in the wide spectrum of disease manifestations it can cause; one of the worst of which is the hypercoagulable state induced by severe infection. This case report focuses on a 33-year-old Hispanic male who developed severe acute respiratory syndrome requiring management with extracorporeal membrane oxygenation (ECMO) and developed deep venous thromboses during severe coronavirus disease 2019 (COVID-19) pneumonia. Since there are no current guideline(s) for routine screening for venous thromboembolism (VTE) in ECMO patients, we aim to highlight a proposed benefit of routine screening for VTE in patients with severe COVID-19 treated with ECMO pre-cannulation and post-decannulation, which minimizes the risk of cannulation-associated complications, as well as the risk of post-decannulation VTE respectively. While VTE is a known complication of ECMO therapy, the rates of increased incidence of VTE in patients with severe COVID-19 make the detection of such complications even more important to reduce overall morbidity and mortality.

Literature Review of COVID-19, Pulmonary and Extrapulmonary Disease.

In December 2019 novel coronavirus-Severe Acute Respiratory Syndrome-Corona Virus2 (SARS-CoV2)-originated from Wuhan, China, and spread rapidly around the world. This literature review highlights the dynamic nature of COVID-19 transmission and presentation. Analyzing 59 relevant articles up to May 1st, 2020 reflects that the main reported clinical manifestation of COVID-19 pandemic is fever and respiratory involvement. Also, current literature demonstrates a wide spectrum of different and atypical presentation(s) of COVID-19. The definite route of SARS-CoV2 transmission is respiratory droplets, however, virus nucleic acid has been detected in the stool and urine specimens as well. The severity of symptoms and outcomes of COVID-19 vary based on the patient's medical background, age, sex, and concurrent medical conditions (e.g. pregnancy). This is the first review that classifies all essential points regarding COVID-19 manifestations at a glance to improve the outcome of the patients by a better insight into diagnosis and management.

3D In Vitro Neuron on a Chip for Probing Calcium Mechanostimulation.

The evolution of tissue on a chip systems holds promise for mimicking the response of biological functionality of physiological systems. One important direction for tissue on a chip approaches are neuron-based systems that could mimic neurological responses and lessen the need for in vivo experimentation. For neural research, more attention has been devoted recently to understanding mechanics due to issues in areas such as traumatic brain injury (TBI) and pain, among others. To begin to address these areas, a 3D Nerve Integrated Tissue on a Chip (NITC) approach combined with a Mechanical Excitation Testbed (MET) System is developed to impose external mechanical stimulation toward more realistic physiological environments. PC12 cells differentiated with nerve growth factor, which were cultured in a controlled 3D scaffolds, are used. The cells are labeled in a 3D NITC system with Fluo-4-AM to examine their calcium response under mechanical stimulation synchronized with image capture. Understanding the neural responses to mechanical stimulation beyond 2D systems is very important for neurological studies and future personalized strategies. This work will have implications in a diversity of areas including tissue-on-a-chip systems, biomaterials, and neuromechanics.

Duration of Dual Antiplatelet Therapy Following Drug-Eluting Stent Implantation: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

To evaluate the efficacy and safety of long-duration dual antiplatelet therapy (L-DAPT) compared to short-duration dual antiplatelet therapy (S-DAPT) after drug-eluting stent implantation. We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials assessing the clinical effect of L-DAPT vs S-DAPT after drug-eluting stent. Efficacy end points were all-cause mortality, cardiac mortality, myocardial infarction (MI), stent thrombosis (ST), and target vessel revascularization (TVR). Safety end points were TIMI major bleeding and stroke. Event rates were compared using a random-effects model. We identified 11 randomized controlled trials in which 33,520 patients were randomized to S-DAPT (N = 16,687) and L-DAPT (n = 16,833), respectively. Compared with L-DAPT, S-DAPT was associated with higher rate of MI and lower rate of TIMI major bleeding (1.40 [1.08-1.81] and 0.60 [0.41-0.89], respectively), without any significant differences in the rate of all-cause mortality, cardiac mortality, ST, TVR, and stroke (0.88 [0.75-1.04], 0.98 [0.79-1.22], 1.54 [0.95-2.50], 0.99 [0.73-1.34], and 1.01 [0.78-1.32], respectively). Our results showed that compared with L-DAPT, S-DAPT was associated with higher rate of MI and lower rate of major bleeding without any significant difference in the rates of all-cause mortality, cardiac mortality, ST, TVR, and stroke.

Changes in parameters of right ventricular function with cardiac resynchronization therapy.

BACKGROUND: Studies have shown that cardiac resynchronization therapy (CRT) significantly improves right ventricle (RV) size and function in patients with heart failure (HF). HYPOTHESIS: CRT does not lead to improvement in RV function independent of baseline clinical variables. METHODS: A systematic search of studies published between 1966 to August 31, 2015 was conducted using Pub Med, CINAHL, Cochrane CENTRAL and the Web of Science databases. Studies reporting tricuspid annular plane systolic excursion (TAPSE) or RV basal strain or RV long axis diameter or RV short axis diameter or RV fractional area change (FAC), before and after CRT, were identified. A meta-analysis was performed using random effects with inverse variance method to determine the pooled mean difference in various parameters of RV function after CRT. Meta-regression analysis was performed to test the relationship between change in various parameters of RV functions after CRT and covariates- age, QRS duration, and left ventricular ejection fraction (LVEF). RESULTS: Thirteen studies (N=1541) were selected for final analysis. CRT therapy led to statistically significant increases in TAPSE [1.21 (95% CI 0.55-1.86; p<0.001)], RV FAC [2.26 (95% CI 0.50-4.01; p<0.001)] and basal strain [2.82 (95% CI 0.59-5.05; p<0.001)] and statistically significant decreases in mean RV long axis diameter [-2.94 (95% CI -5.07- -0.82; p=0.005)] and short axis diameter [-1.39 (95% CI -2.10- -0.67; p=0.876)] after a mean follow up period of 9 months. However, after meta-regression analysis for age, QRS duration, and baseline LVEF as covariates, there was no significant improvement in any of the parameters of RV function after CRT. CONCLUSION: There was a statistically significant improvement in TAPSE, RV basal strain, RV fractional area, RV long axis and short axis with CRT. However, improvement in these echocardiographic parameters of RV function after CRT was not independent of baseline clinical variables but statistically dependent on age, QRS duration and baseline LVEF.

Duration of Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Patients With and Without Acute Coronary Syndrome: A Systematic Review of Randomized Controlled Trials.

In this systemic review we evaluated the efficacy and safety of long duration dual anti-platelet therapy (DAPT) (L-DAPT) compared with short duration DAPT (S-DAPT) after drug-eluting stent (DES) implantation in patients who presented with or without acute coronary syndromes (ACS). We identified 8 randomized controlled trials in which 30,975 patients were randomized to S-DAPT versus L-DAPT (12,421 ACS and 18,554 non-ACS). Short duration dual anti-platelet therapy was associated with an increase in target vessel revascularization (TVR) in ACS patients, but the difference was not significant for non-ACS patients (odds ratio [OR] 5.04 [95% CI, 1.28-19.76], and OR, 0.89 [95% CI, 0.51-1.55], respectively). The risk of cardiac mortality was not significantly different with S-DAPT and L-DAPT for ACS (OR, 1.69 [95% CI, 0.82-3.50]) and non-ACS patients (OR, 0.89 [95% CI, 0.57-1.37]). For all cause mortality, myocardial infarction, and stent thrombosis, most of the events were derived from the DAPT study, thus a meta-analysis was not performed for these end points. Based on our review of the literature, we conclude that S-DAPT was associated with higher rates of stent thrombosis and myocardial infarction, and non-significant differences in all-cause mortality, with no significant interactions according to ACS vs non-ACS. However, in non-ACS patients, the benefit-risk profile favored S-DAPT, with lower all-cause mortality, whereas the trends were reversed in ACS. Additional studies are required to determine if the benefit-risk profile of S-DAPT vs L-DAPT varies according to clinical syndrome.

Duration of dual antiplatelet therapy after various drug-eluting stent implantation.

OBJECTIVE: To evaluate efficacy and safety of long duration dual anti-platelet therapy i.e., >12months (L-DAPT) and short duration DAPT i.e., ≤12months (S-DAPT) after various drug-eluting stent (DES) implantation. METHODS: We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) assessing the effect of L-DAPT versus S-DAPT after sirolimus-eluting (Cypher®); paclitaxel-eluting stents (Taxus®); zotarolimus-eluting (Endeavor®) and everolimus-eluting stents (Xience V®) implantation. Odds ratio (OR) and 95% confidence intervals (CI) were calculated using random-effects models. Subgroup analyses were performed comparing two second generation DES and for RCTs comparing S-DAPT and L-DAPT. RESULTS: We included six RCTs that randomized 19,012 patients to S-DAPT versus L-DAPT (4638 in first generation DES; 14,374 in second generation DES; 8099 EES; 4876 in ZES). Compared with L-DAPT, S-DAPT was associated with a higher rate of myocardial infarction (MI) and stent thrombosis (ST) after first [2.65 (1.88, 3.73) and 3.85 (2.14-6.93) respectively] and a higher rate of MI after second generation DES [1.33 (1.06, 1.67)]. There were no significant differences in the rates of all cause mortality, cardiovascular (CV) mortality and stroke with L-DAPT and S-DAPT after implantation of first [0.97 (0.52, 1.81); 1.19 (0.52-2.70); and 1.12 (0.36-3.52) respectively] and second generation DES [0.93 (0.69, 1.25); 0.93 (0.63, 1.36); and 0.58 (0.19, 1.75), respectively]. On further analysis of type of second generation DES, S-DAPT continues to show a higher rate of MI and ST after EES implantation [1.54 (1.11, 2.13) and 2.68 (1.20-5.94) respectively]; however there was no significant difference in the rate of MI and ST with S-DAPT and L-DAPT after ZES implantation [1.07 (0.44, 2.61) and 1.11(0.39, 3.13), respectively]. CONCLUSION: 1) Compared with L-DAPT, S-DAPT was associated with a higher rate of MI without any significant difference in the rate of all cause mortality, CV mortality and stroke after first and second generation DES. 2) Rate of ST was also higher with S-DAPT compared to L-DAPT after first generation DES implantation; however, it was not significantly different after second generation DES. 3) On further subgroup analysis of second-generation stent there was no significant difference in the rate of all cause mortality, CV mortality, MI, ST and stroke with S-DAPT and L-DAPT after ZES implantation. S-DAPT may be optimal for newer generation stents particularly ZES.