Surface engineered nanohybrids in plasmonic photothermal therapy for cancer: Regulatory and translational challenges.

Plasmonic materials as non-invasive and selective treatment strategies are gaining increasing attention in the healthcare sector due to their remarkable optical and electronic properties, where the interface between matter and light becomes enhanced and highly localized. Some attractive applications of plasmonic materials in healthcare include drug delivery to target specific tissues or cells, hence reducing the side effects of the drug and improving their efficacy; enhancing the contrast and resolution in bioimaging; and selectively heating and destroying the cancerous cells while parting the healthy cells. Despite such advancements in photothermal therapy for cancer treatment, some limitations are still challenging. These include poor photothermal conversion efficiency, heat resistance, less accumulation in the tumor microenvironment, poor biosafety of photothermal agents, damage to the surrounding healthy tissues, post-treatment inflammatory responses, etc. Even though the clinical application of photothermal therapy is primarily restricted due to poor tissue penetration of excitation light, enzyme therapy is hindered due to less therapeutic efficacy. Several multimodal strategies, including chemotherapy, radiotherapy, photodynamic therapy, and immunotherapy were developed to circumvent these side effects associated with plasmonic photothermal agents for effective mild-temperature photothermal therapy. It can be prophesied that the nanohybrid platform could pave the way for developing cutting-edge multifunctional precise nanomedicine via an ecologically sustainable approach towards cancer therapy. In the present review, we have highlighted the significant challenges of photothermal therapy from the laboratory to the clinical setting and their struggle to get approval from the Food and Drug Administration (FDA).

Targeted delivery of ursolic acid and oleanolic acid to lungs in the form of an inhaler for the management of tuberculosis: Pharmacokinetic and toxicity assessment.

INTRODUCTION: Ursolic acid (UA) and oleanolic acid (OA) are triterpenoids. They are used to treat numerous diseases, including tuberculosis. Combinations of these drugs provide new insight into the management of tuberculosis. The major obstacle is the effective delivery of these drugs to the lungs, which are mainly affected due to M. tuberculosis. A metered-dose inhaler (MDI) was developed to address this issue containing UA and OA, followed by in-vitro and in-vivo evaluation. METHODS: In the present study, MDI formulation was prepared by incorporating UA and OA at the dose level of 120 µg/ml in each actuation. In-vitro evaluation of this MDI formulation was performed to ensure its suitability to deliver UA and OA preciously. With prior approval of IAEC, a pharmacokinetic and acute inhalation toxicity study was conducted using MDI on Wistar rats. RESULTS: The pharmacokinetic study showed an increased biological half-life of UA (9.23±0.104 h) and OA (8.93±0.166 h) in combination therapy. In-vivo toxicity study demonstrated no adverse effects on body weight and vital organs in the treatment group compared with the control group. Histopathology examination of these essential organs showed no abnormalities. Mild alternation in the biochemical and hematological parameters was observed. However, these alterations did not affect the overall health of the animals. CONCLUSION: The present study documents a detailed study for the safety and pharmacokinetics of UA and OA in-vivo for their advanced application in tuberculosis disease.

Continuous flow scale-up of biofunctionalized defective ZnO quantum dots: A safer inorganic ingredient for skin UV protection.

The versatility of ZnO quantum dots (QDs) exhibiting size-tunable visible photoluminescence has propelled them to the forefront of leading-edge innovations in healthcare. At the nano-bio interface, enhancing the singly-ionized oxygen vacancy defects (VO•) through holistic, sustainable synthesis protocols driven by the synergistic influence of QDs' nucleation-growth kinetics has implications on their bioactivity, physiochemical, and optical performance. Recently, robust continuous flow platforms have transcended the conventional batch reactors by alleviating the concerns of "hot-spot" formation due to inhomogeneous heat distribution, acute energy consumption, poor quality, and yield. However, complexities exist in translating batch chemistries into flow processes. Here, a unique, rationally designed continuous flow synthesis of luminescent defect-engineered ZnO QDs (E-QDs) via helical-reactor assembly that can adequately synthesize on a large scale is reported. The crux of this lies in the amalgamation of "green chemistry" and flow synthesis, which results in Lamer-mechanism mediated monodispersed E-QDs demonstrating high photoluminescence quantum yield (PLQY) of 89% under an accurately regulated synthesis environment. Process intensification corroborated that the bio-stable E-QDs manifested admirable photostability, broad-spectrum UV-shielding (400-250 nm), colloidal stability, in vitro biocompatibility against L929 and HaCaT cells, and antioxidant activity. These attributes were better compared to the commercial ZnO nanoparticles (ZnOC-NPs) used for skin UV protection. Delving deeper, the main drivers for the high density of intrinsic VO• formation (Iv/Io∼42.5) were revealed to be the reactor's hydrodynamic performance and the improvised heating rate (2.5°C/sec). Hence, these E-QDs have potential as a new, safe, and economical multifunctional active ingredient for skin UV protection and antioxidants for treating ROS-mediated disorders. STATEMENT OF SIGNIFICANCE: UV filters exhibiting questionable UV-attenuation efficacy and phototoxicity are significant impediments to the healthcare industry emphasizing skin cancer prevention. Although least explored, VO•-governed aberrant photoactive, biological, and surface-reactive qualities of engineered ZnO QDs (E-QDs) have created ample room to investigate these hallmarks for skin UV protection. However, the bottlenecks in stereotypical ZnO QDs production confined by inefficient process control are annihilated by continuous flow strategies. Herein, the high-throughput continuous flow helical reactor assembly was designed and fabricated to successfully showcase optimized transport properties, reproducibility, yield, and quality E-QDs. Anticipating a skyrocketing demand for E-QDs as bioactive-sunscreen components, the comprehensive investigation has demonstrated unprecedented biofunctionality and ROS-scavenging behaviour, even upon UVR exposure, contrary to the traditional nanoparticulate ZnO UV filters.

Drugs repurposing for SARS-CoV-2: new insight of COVID-19 druggability.

INTRODUCTION: The ongoing epidemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) creates a massive panic worldwide due to the absence of effective medicines. Developing a new drug or vaccine is time-consuming to pass safety and efficacy testing. Therefore, repurposing drugs have been introduced to treat COVID-19 until effective drugs are developed. AREA COVERED: A detailed search of repurposing drugs against SARS-CoV-2 was carried out using the PubMed database, focusing on articles published 2020 years onward. A different class of drugs has been described in this article to target hosts and viruses. Based on the previous pandemic experience of SARS-CoV and MERS, several antiviral and antimalarial drugs are discussed here. This review covers the failure of some repurposed drugs that showed promising activity in the earlier CoV-pandemic but were found ineffective against SARS-CoV-2. All these discussions demand a successful drug development strategy for screening and identifying an effective drug for better management of COVID-19. EXPERT OPINION: Repurposed drugs have been used since COVID-19 to eradicate disease propagation. Drugs found effective for MERS and SARS may not be effective against SARS-CoV-2. Drug libraries and artificial intelligence are helpful tools to screen and identify different molecules targeting viruses or hosts.

Designing nanoformulation for the nose-to-brain delivery in Parkinson's disease: Advancements and barrier.

Parkinson's disease (PD), a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, which results in the loss of motor activity. In the management of PD, the primary aim is to increase the dopamine content in the brain either by delivering the precursors of dopamine or by inhibiting the molecules responsible for dopamine degradation. Due to the low bioavailability, a higher dosage of drugs needs to be administered repeatedly for achieving the desired therapeutic effect. This repeated high dose not only increases the severe side effects but also produces tolerance in the body. Often, direct administration of drugs fails to ameliorate the symptoms as the unmodified drugs cannot cross the blood-brain barrier (BBB). Nanotherapeutic is at the forefront of the alternative treatment against the central nervous system (CNS) disorders due to the ability to circumvents the BBB. Here, all the available treatments for PD have been discussed with their limitation. The current trends of nanotherapeutics for PD have been explored. Suitability and formulation prospects for nasal delivery have been analyzed in detail to explore new research scope. The most effective approach is the nose-to-brain delivery for targeting drugs directly to the brain. This delivery bypasses the BBB and concentrates more drugs at the target site. Thus, developments of nose-to-brain delivery of nanoformulations explicit the new scope to manage PD better. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Opportunistic etiological agents causing lung infections: emerging need to transform lung-targeted delivery.

Lung diseases continue to draw considerable attention from biomedical and public health care agencies. The lung with the largest epithelial surface area is continuously exposed to the external environment during exchanging gas. Therefore, the chances of respiratory disorders and lung infections are overgrowing. This review has covered promising and opportunistic etiologic agents responsible for lung infections. These pathogens infect the lungs either directly or indirectly. However, it is difficult to intervene in lung diseases using available oral or parenteral antimicrobial formulations. Many pieces of research have been done in the last two decades to improve inhalable antimicrobial formulations. However, very few have been approved for human use. This review article discusses the approved inhalable antimicrobial agents (AMAs) and identifies why pulmonary delivery is explored. Additionally, the basic anatomy of the respiratory system linked with barriers to AMA delivery has been discussed here. This review opens several new scopes for researchers to work on pulmonary medicines for specific diseases and bring more respiratory medication to market.

Intervention of 3D printing in health care: transformation for sustainable development.

INTRODUCTION: Three-dimensional (3D) technology is the practice of dropping material layer-by-layer in the construction of the desired object. The application of the 3D printing technique has been observed in miscellaneous domains. Personalized medicine becomes the most demanding trend in the health-care segment. Several advancements have been observed in the progress of 3D printing. However, the availability of finished products in the marketplace is very less. There is an utmost requirement to improve the knowledge and skills in the sustainable development of pharmaceutical and medical products by selecting suitable techniques and materials. AREAS COVERED: This article covers the fundamental process of 3D printing, types, pharmaceutical-medical application, benefits, and challenges. EXPERT OPINION: This technology is capable of designing the complex geometry of an organ. It is feasible to produce drug products by incorporating multiple drugs in various compartments in such a fashion that these drugs can release from the compartment at a predetermined rate. Additionally, this 3D process has the potential to revolutionize personalized therapy to different age-groups through design flexibility and accurate dosing. In the upcoming years, the potential application of this technology can be seen in a clinical setting where patients will get individualized medicine as per their needs.

Status of inhalable antimicrobial agents for lung infection: progress and prospects.

Introduction: Available parenteral and oral administration of antimicrobial agents (AMAs) in respiratory infections often show less penetration into the lung parenchyma. Due to inappropriate dose availability, the rate of antibiotic resistance is increasing gradually. Inhaled antibiotics intensely improve the availability of drugs at the site of respiratory infections. This targeted delivery minimizes systemic exposure and associated toxicity.Area covers: This review was performed by searching in the scientific database like PubMed and several trusted government sites like fda.gov, cdc.gov, ClinicalTrials.gov, etc. For better understanding, AMAs are classified in different stages of approval. Mechanism and characterization of pulmonary drug deposition section helps to understand the effective delivery of AMAs to the respiratory tract. There is a need for proper adoption of delivery devices for inhalable AMAs. Thus, delivery devices are extensively explained. Inspiratory flow has a remarkable impact on the delivery device that has been explained in detail.Expert opinion: Pulmonary delivery restricts the bulk administration of drugs in comparison with other routes. Therefore, novel AMAs with higher bactericidal activity at lower concentrations need to be synthesized. Extensive research is indeed in developing innovative delivery devices that would able to deliver higher doses of AMAs through the pulmonary route.

Emerging therapeutics for the management of COVID 19.

INTRODUCTION: The coronavirus-19 (COVID-19) disease pandemic can be characterized as the most critical and changeable hazard to healthcare systems in eras. The high fatality rate associated with coronavirus infection underlines the urgent need for an effective treatment to reduce disease severity and mortality. AREAS COVERED: A detailed search for treatments related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) was carried out using PubMed. Components of the virus relevant to the infectious mechanism were identified. We have highlighted all the latest emerging and repurposed drugs that were found to be active against this novel coronavirus and classified these drugs according to their category. Different drug targets are discussed in order to identify new molecules or new combinations as candidates to manage SARS-CoV2/COVID-19 infections. EXPERT OPINION: The development of novel molecules and vaccines has been a challenge during this urgent crisis. Nucleoside analogs and IL-6 receptor antagonists have been identified as the best candidates for treatment of this disease. Multi-drug therapy by targeting different pathways will need to be corroborated and then confirmed through clinical trials. Until a vaccine is available, an alternative drug regimen needs to be adopted by clinicians in the management of coronavirus symptoms.

Development and evaluation of Chitosan nanoparticles based dry powder inhalation formulations of Prothionamide.

Prothionamide (PTH), a second line antitubercular drug is used to administer in conventional oral route. However, its unpredictable absorption and frequent administration limit its use. An alternate approach was thought of administering PTH through pulmonary route in a form of nanoparticles, which can sustain the release for several hours in lungs. Chitosan, a bio-degradable polymer was used to coat PTH and further freeze dried to prepare dry powder inhaler (DPI) with aerodynamic particle size of 1.76µm. In vitro release study showed initial burst release followed by sustained release up to 96.91% in 24h. In vitro release further correlated with in vivo study. Prepared DPI maintained the PTH concentration above MIC for more than 12h after single dose administration and increased the PTH residency in the lungs tissue more than 24h. Animal study also revealed the reduction of dose in pulmonary administration, which will improve the management of tuberculosis.

PLGA Ethionamide Nanoparticles for Pulmonary Delivery: Development and in vivo evaluation of dry powder inhaler.

PLGA (50:50) nanoparticles were prepared to sustain the release of Ethionamide in order to decrease the dose and dosing frequency. It further modified in the form of dry powder inhaler to make suitable for pulmonary administration and increase drug residency in lungs. Ethionamide loaded PLGA nanoparticles were prepared by solvent evaporation method. Freeze dried nanoparticles and anhydrous inhalable grade lactose were mixed manually using geometrical dilution process to modify the nanoparticles in the form of dry powder inhaler. Animal study was conducted to correlate between in-vivo and in-vitro. PLGA nanoparticles showed initial burst release followed by zero order release up to 95.17±3.59% in 24h. Aerodynamic particle size of optimized dry powder inhaler was found as 1.79µm. There was no significant aggregation of dry powder inhaler during 6 months of stability study. Area under the concentration-time curve from 0h to infinity (AUC0-∞) signifies the prolong residency of ETH in body compartment, revealed from animal study. PLGA 50:50 coated nanoparticles released Ethionamide for the period of 24h in simulated lungs fluid. Correlation between in-vitro dissolution and in-vivo study was established after performing animal study. Prepared dry powder inhaler maintained Ethionamide concentration above minimum inhibitory concentration for more than 12h after single dose administration.