Implication of metabolomics and transporter modulation based strategies to minimize multidrug resistance and enhance site-specific bioavailability: a needful consideration toward modern anticancer drug discovery.

Induction of drug-metabolizing enzymes and efflux transporters (DMET) through activation of pregnane x receptor (PXR) is the primary factor involved in almost all bioavailability and drug resistance-related problems of anticancer drugs. PXR is a transcriptional regulator of many metabolizing enzymes and efflux transporters proteins like p-glycoprotein (p-gp), multidrug resistant protein 1 and 2 (MRP 1 and 2), and breast cancer resistant protein (BCRP), etc. Several anticancer drugs are potent activators of PXR receptors and can modulate the gene expression of DMET proteins. Involvement of anticancer drugs in transcriptional regulation of DMET can prompt increased metabolism and efflux of their own or other co-administered drugs, which leads to poor site-specific bioavailability and increased drug resistance. In this review, we have discussed several novel strategies to evade drug-induced PXR activation and p-gp efflux including assessment of PXR ligand and p-gp substrate at early stages of drug discovery. Additionally, we have critically discussed the chemical structure and drug delivery-based approaches to avoid PXR binding and inhibit the p-gp activity of the drugs at their target sites.

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model.

Diabetic nephropathy (DN), a chronic progressive kidney disease, is a significant complication of diabetes mellitus. Dysregulation of the histone deacetylases (HDACs) gene has been implicated in the pathogenesis of DN. Hence, the HDAC-inhibitors have emerged as a critical class of therapeutic agents in DN; however, the currently available HDAC4-inhibitors are mostly nonselective in nature as well as inhibit multiple HDACs. RNA interference of HDAC4 (HDAC4 siRNA) has shown immense promise, but the clinical translation has been impeded due to lack of a targeted, specific, and in vivo applicable delivery modality. In the present investigation, we examined Cyclo(RGDfC) (cRGD) truncated polymeric nanoplex with dendrimeric templates for targeted HDAC4 Gene Silencing. The developed nanoplex exhibited enhanced encapsulation of siRNA and offered superior protection against serum RNase nucleases degradation. The nanoplex was tested on podocytes (in vitro), wherein it showed selective binding to the αvß3 integrin receptor, active cellular uptake, and significant in vitro gene silencing. The in vivo experiments showed remarkable suppression of the HDAC4 and inhibition in the progression of renal fibrosis in the Streptozotocin (STZ) induced DN C57BL/6 mice model. Histopathological and toxicological studies revealed nonsignificant abnormality/toxicity with the nanoplex. Conclusively, nanoplex was found as a promising tactic for targeted therapy of podocytes and could be extended for other kidney-related ailments.

Discovery of boronic acid-based potent activators of tumor pyruvate kinase M2 and development of gastroretentive nanoformulation for oral dosing.

Several studies have established that cancer cells explicitly over-express the less active isoform of pyruvate kinase M2 (PKM2) is critical for tumorigenesis. The activation of PKM2 towards tetramer formation may increase affinity towards phosphoenolpyruvate (PEP) and avoidance of the Warburg effect. Herein, we describe the design, synthesis, and development of boronic acid-based molecules as activators of PKM2. The designed molecules were inspired by existing anticancer scaffolds and several fragments were assembled in the derivatives. 6a-6d were synthesized using a multi-step synthetic strategy in 55-70% yields, starting from cheap and readily available materials. The compounds were selectively cytotoxic to kill the cancerous cells at 80 nM, while they were non-toxic to the normal cells. The kinetic studies established the compounds as novel activators of PKM2 and (E/Z)-(4-(3-(2-((4-chlorophenyl)amino)-4-(dimethylamino)thiazol-5-yl)-2-(ethoxycarbonyl)-3-oxoprop-1-en-1-yl) phenyl)boronic acid (6c) emerged as the most potent derivative. 6c was further evaluated using various in silico tools to understand the molecular mechanism of tetramer formation. Docking studies revealed that 6c binds to the PKM2 dimer at the dimeric interface. Further to ascertain the binding site and mechanism of action, rigorous MD (molecular dynamics) simulations were undertaken, which led to the conclusion that 6c stabilizes the center of the dimeric interface that possibly promotes tetramer formation. We further planned to make a tablet of the developed molecule for oral delivery, but it was seriously impeded owing to poor aqueous solubility of 6c. To improve aqueous solubility and retain 6c at the lower gastrointestinal tract, thiolated chitosan-based nanoparticles (TCNPs) were prepared and further developed as tablet dosage form to retain anticancer potency in the excised goat colon. Our findings may provide a valuable pharmacological mechanism for understanding metabolic underpinnings that may aid in the clinical development of new anticancer agents targeting PKM2.

Generation dependent safety and efficacy of folic acid conjugated dendrimer based anticancer drug formulations.

PURPOSE: Folate conjugated poly(propyleneimine) (PPI) dendrimer (FPPI) mediated anticancer therapy is being extensively discovered throughout the world. The present investigation was aimed at exploring the targeting potential of Melphalan loaded FPPI of different generations (MP-FPPI) for effective management of cancer. METHODS: The MP-FPPI formulations were compared for drug entrapment efficiency, in vitro release profile, toxicology, folate receptor blockage assay, cell uptake assay, stability studies, and in vivo studies. RESULTS: Upon increasing the dendrimer generation from fourth to fifth, the drug delivery parameters improved negligibly except the toxicological profile that improved exponentially. MTT assay in case of MCF-7 cells depicted the IC 50 values of 8 ± 0.15, 0.9 ± 0.02, 0.2 ± 0.01 and 10 ± 0.17 µM, respectively in case of MP-FPPI3, MP-FPPI4, MP-FPPI5, and free Melphalan suggesting folate based targeting to be the efficacious approach to kill cancer cells. The median survival time for tumor bearing mice treated with MP-FPPI3, MP-FPPI4, MP-FPPI5 and free drug was found to be 23, 59, 62 and 26 days, respectively. CONCLUSIONS: The study concludes fourth generation PPI dendrimer to be superior carrier for folate based tumor targeting compared to third and fifth generation based formulations. This work is expected to provide a significant clue in the selection of "dendrimer generation" for folate mediated cancer targeting therapy.

Dendrimer-stabilized smart-nanoparticle (DSSN) platform for targeted delivery of hydrophobic antitumor therapeutics.

PURPOSE: To formulate dendrimer-stabilized smart-nanoparticle (DSSN; pD-ANP-f) for the targeted delivery of the highly hydrophobic anticancer drug, Paclitaxel (PTXL). METHOD: The developed nanoformulations were evaluated for particle size, surface-charge, loading efficiency, particle density, in-vitro drug release, SEM/TEM, cytotoxicity assay, fluorescence uptake, HPLC quantitative cell uptake assay, flow cytometry, tubulin polymerization, and stability assessments. RESULTS: The developed pD-ANP-f nanoformulation (135.17 ± 7.39 nm; -2.05 ± 0.37 mV and 80.11 ± 4.39% entrapment) exhibited a pH-dependent drug release; remained stable in physiological pH, while rapid releasing PTXL under tumorous environment (pH 5.5). The cytotoxicity assay performed in cervical, breast, blood, and liver cancer cell lines showed pD-ANP-f to be strongly suppressing the growth of cancer cells. We investigated the fluorescence based intracellular trafficking and HPLC based cellular uptake of nanoformulated drug and the result indicates higher cellular uptake of pD-ANP-f compared to other formulations. pD-ANP-f prominently induced apoptosis (73.11 ± 3.84%) and higher polymerization of tubulins (59.73 ± 6.22%). DSSN nanoformulation was found to be extremely biocompatible (<1% hemolytic) compared to naked PTXL (19.22 ± 1.01%) as well as PTXL-dendrimer nanocomplex (8.29 ± 0.71%). CONCLUSION: DSSN strategy is a novel and promising platform for biomedical applications that can be effectively engaged for the delivery of drug/gene/siRNA targeting.

Glycyrrhizin Conjugated Dendrimer and Multi-Walled Carbon Nanotubes for Liver Specific Delivery of Doxorubicin.

The purpose of the present investigation was to investigate the drug targeting potential of glycyrrhizin (GL) conjugated dendrimers (GL-PPI) and multi walled carbon nanotubes (GL-MWCNTs) towards liver targeting of a model anti-cancer agent, doxorubicin (DOX). The synthesis was confirmed by FTIR, 1H-NMR and morphology analysis. Higher DOX loading was observed in case of GL-PPI-DOX and GL-MWCNT-DOX (43.02 ± 0.64% and 87.26 0.57%, respectively) than parent nanocarriers. GL attachment considerably reduced the haemolytic toxicity of DOX by 12.38 ± 1.05 and 7.30 ± 0.63% by GL-PPI-DOX and GL-MWCNT-DOX, respectively. MTT cytotoxicity studies, flow cytometry and cell morphology assessment was done in HepG2 cell. The IC50 of DOX was reduced from 4.19±0.05 µM to 2.0±0.01 and 2.7±0.03 µM, respectively by GL-PPI-DOX and GL-MWCNT-DOX, respectively. Flow cytometry and phase contrast microscopy confirmed GL conjugated formulations to be significantly dragging higher cancer cell number of cells in early apoptosis as well as in early apoptotic phase.

One platform comparison of solubilization potential of dendrimer with some solubilizing agents.

OBJECTIVE: To compare various solubilizing agents for their solubilizing propensity as well as effect of pH, concentration and time on solubility of a highly hydrophobic drug. MATERIALS AND METHODS: Dendrimers were synthesized by divergent method. Solubilization studies were carried out at different pH, concentration and time using Paclitaxel (PTX) as model drug. Hemolytic toxicity study was also performed. RESULTS: The solubility of PTX was increased with increasing concentration of solubilizing agents and the order of solubility enhancement effect of different solubilizing agents was found to be in the following order: fifth generation (5.0 G) poly(propylene imine) (PPI) dendrimers > ß-CD > Tween 80 > polyethylene glycol 6000. The solubility of PTX was found to be highest at pH 5.0 followed by pH 7.4 than pH 9.2. The result of hemolytic toxicity studies displayed that when these solubilizing agents are given in combination with PTX, the toxicity was found to be reduced as compare to plain drug. CONCLUSIONS: The solubility of PTX was found to be significantly higher in the presence of 5.0 G PPI dendrimers as compared to the other solubilizing agents. It is also concluded that 5.0 G PPI dendrimers not only enhanced the solubility of PTX many folds but also reduced the toxicity of PTX.

Designing hybrid onconase nanocarriers for mesothelioma therapy: a Taguchi orthogonal array and multivariate component driven analysis.

Onconase (ONC) is a member of a ribonuclease superfamily that has cytostatic activity against malignant mesothelioma (MM). The objective of this investigation was to develop bovine serum albumin (BSA)-chitosan based hybrid nanoformulations for the efficient delivery of ONC to MM while minimizing the exposure to normal tissues. Taguchi orthogonal array L9 type design was used to formulate ONC loaded BSA nanocarriers (ONC-ANC) with a mean particle size of 15.78 ± 0.24 nm (ζ = -21.89 ± 0.11 mV). The ONC-ANC surface was hybridized using varying chitosan concentrations ranging between 0.100 and 0.175% w/v to form various ONC loaded hybrid nanocarriers (ONC-HNC). The obtained data set was analyzed by principal component analysis (PCA) and principal component regressions (PCR) to decode the effects of investigated design variables. PCA showed positive correlations between investigated design variables like BSA, ethanol dilution, and total ethanol with particle size and entrapment efficiency (EE) of formulated nanocarriers. PCR showed that the particle size depends on BSA, ethanol dilution, and total ethanol content, while EE was only influenced by BSA content. Further analysis of chitosan and TPP effects used for coating of ONC-ANC by PCR confirmed their positive impacts on the particle size, zeta potential, and prolongation of ONC release compared to uncoated ONC-ANC. PCR analysis of preliminary stability studies showed increase in the particle size and zeta potential at lower pH. However, particle size, zeta potential, and EE of developed HNC were below 63 nm, 31 mV, and 96%, respectively, indicating their stability under subjected buffer conditions. Out of the developed formulations, HNC showed enhanced inhibition of cell viability with lower IC50 against human MM-REN cells compared to ONC and ONC-ANC. This might be attributed to the better cell uptake of HNC, which was confirmed in the cell uptake fluorescence studies. These studies indicated that a developed nanotherapeutic approach might aid in reducing the therapeutic dose of ONC, minimizing adverse effects by limiting the exposure of ONC to normal tissues, and help in the development of new therapeutic forms and routes of administration.

On-demand Opto-Laser activatable nanoSilver ThermoGel for treatment of full-thickness diabetic wound in a mouse model.

Patients suffering from diabetes mellitus are prone to develop diabetic wounds that are non-treatable with conventional therapies. Hence, there is an urgent need of hour to develop the therapy that will overcome the lacunas of conventional therapies. This investigation reports the Quality by Design-guided one-pot green synthesis of unique Opto-Laser activatable nanoSilver ThermoGel (OL→nSil-ThermoGel) for hyperthermia-assisted treatment of full-thickness diabetic wounds in mice models. The characterization findings confirmed the formation of spherical-shaped nanometric Opto-Laser activatable nanoSilver (30.75 ± 2.7 nm; ∆T: 37 ± 0.2 °C â†’ 66.2 ± 0.1 °C; at 1.8 W/cm2 NIR laser density). The findings indicated acceptable in vitro cytocompatibility and significant keratinocyte migration (95.04 ± 0.07 %) activity of OL→nSil towards HaCaT cells. The rheological data of OL→nSil hybridized in situ thermoresponsive gel (OL→nSil-ThermoGel) showed the gelling temperature at 32 ± 2 °C. In vivo studies on full-thickness diabetic wounds in a Mouse model showed OL→nSil-ThermoGel accelerated wound closure (94.42 ± 1.03 %) and increased collagen synthesis, angiogenesis, and decreased inflammatory markers. Similarly, immunohistochemistry study showed significant angiogenesis and faster phenotypic switching of fibroblasts to myofibroblasts in OL→nSil-ThermoGel treated diabetic wounds. Histological evaluation revealed a marked rise in keratinocyte migration, organized collagen deposition, and early regeneration of the epithelial layer compared to the diabetic wound control. In conclusion, the OL→nSil-ThermoGel modulates the cytokines, re-epithelialization, protein expression, and growth factors, thereby improving the repair and regeneration of diabetic wounds in mice.

Refinement of safety and efficacy of anti-cancer chemotherapeutics by tailoring their site-specific intracellular bioavailability through transporter modulation.

Low intracellular bioavailability, off-site toxicities, and multi drug resistance (MDR) are the major constraints involved in cancer chemotherapy. Many anticancer molecules fail to become a good lead in drug discovery because of their poor site-specific bioavailability. Concentration of a molecule at target sites is largely varied because of the wavering expression of transporters. Recent anticancer drug discovery strategies are paying high attention to enhance target site bioavailability by modulating drug transporters. The level of genetic expression of transporters is an important determinant to understand their ability to facilitate drug transport across the cellular membrane. Solid carrier (SLC) transporters are the major influx transporters involved in the transportation of most anti-cancer drugs. In contrast, ATP-binding cassette (ABC) superfamily is the most studied class of efflux transporters concerning cancer and is significantly involved in efflux of chemotherapeutics resulting in MDR. Balancing SLC and ABC transporters is essential to avoid therapeutic failure and minimize MDR in chemotherapy. Unfortunately, comprehensive literature on the possible approaches of tailoring site-specific bioavailability of anticancer drugs through transporter modulation is not available till date. This review critically discussed the role of different specific transporter proteins in deciding the intracellular bioavailability of anticancer molecules. Different strategies for reversal of MDR in chemotherapy by incorporation of chemosensitizers have been proposed in this review. Targeted strategies for administration of the chemotherapeutics to the intracellular site of action through clinically relevant transporters employing newer nanotechnology-based formulation platforms have been explained. The discussion embedded in this review is timely considering the current need of addressing the ambiguity observed in pharmacokinetic and clinical outcomes of the chemotherapeutics in anti-cancer treatment regimens.

Advancement in Analytical Strategies for Quantification of Biomarkers with a Special Emphasis on Surrogate Approaches.

Accurate quantification of biomarkers has always been a challenge for many bioanalytical scientists due to their endogenous nature and low concentration in biological matrices. Different analytical approaches have been developed for quantifying biomarkers including enzyme-linked immunosorbent assay, immunohistochemistry, western blotting, and chromatographic techniques assisted with mass spectrometry. Liquid chromatography-tandem mass spectrometry-based quantification of biomarkers has gained more attention over other traditional techniques due to its higher sensitivity and selectivity. However, the primary challenge lies with this technique includes the unavailability of a blank matrix for method development. To overcome this challenge, different analytical approaches are being developed including surrogate analyte and surrogate matrix approach. Such approaches include quantification of biomarkers in a surrogate matrix or quantification of an isotopically labeled surrogate analyte in an authentic matrix. To demonstrate the authenticity of the surrogate approach, it is mandatory to establish quantitative parallelism through validation employing respective surrogate analytes and surrogate matrices. In this review, different bioanalytical approaches for biomarker quantification and recent advancements in the field aiming for improvement in the specificity of the techniques have been discussed. Liquid chromatography-tandem mass spectrometry-based surrogate approaches for biomarker quantification and significance of parallelism establishment in both surrogate matrix and surrogate analyte-based approaches have been critically discussed. In addition, different methods for demonstrating parallelism in the surrogate method have been explained.

Stimuli-Responsive Nanotherapeutics for Treatment and Diagnosis of Stroke.

Stroke is the second most common medical emergency and constitutes a significant cause of global morbidity. The conventional stroke treatment strategies, including thrombolysis, antiplatelet therapy, endovascular thrombectomy, neuroprotection, neurogenesis, reducing neuroinflammation, oxidative stress, excitotoxicity, hemostatic treatment, do not provide efficient relief to the patients due to lack of appropriate delivery systems, large doses, systemic toxicity. In this context, guiding the nanoparticles toward the ischemic tissues by making them stimuli-responsive can be a turning point in managing stroke. Hence, in this review, we first outline the basics of stroke, including its pathophysiology, factors affecting its development, current treatment therapies, and their limitations. Further, we have discussed stimuli-responsive nanotherapeutics used for diagnosing and treating stroke with challenges ahead for the safe use of nanotherapeutics.

Ethosomes and ultradeformable liposomes for transdermal delivery of clotrimazole: A comparative assessment.

THE OBJECTIVE OF WORK WAS TO FORMULATE, EVALUATE AND COMPARE THE TRANSDERMAL POTENTIAL OF NOVEL VESICULAR NANOCARRIERS: ethosomes and ultradeformable liposomes, containing clotrimazole (CLT), an anti-fungal bioactive. The ethosomal formulation (ET4) and ultradeformable liposomal (UL) formulation (TT3) showed highest entrapment 68.73 ± 1.4% and 55.51 ± 1.7%, optimal nanometric size range 132 ± 9.5 nm and 121 ± 9.7 nm, and smallest polydispersity index 0.027 ± 0.011 and 0.067 ± 0.009, respectively. The formulation ET4 provided enhanced transdermal flux 56.25 ± 5.49 µg/cm(2)/h and decreased the lag time of 0.9 h in comparison to TT3 formulation (50.16 ± 3.84 µg/cm(2)/h; 1.0 h). Skin interaction and FT-IR studies revealed greater penetration enhancing effect of ET4 than TT3 formulation. ET4 formulation also had the highest zone of inhibition (34.6 ± 0.57 mm), in contrast to TT3 formulation (29.6 ± 0.57 mm) and marketed cream formulation (19.0 ± 1.00 mm) against candidal species. Results suggested ethosomes to be the most proficient carrier system for dermal and transdermal delivery of clotrimazole.

A Critical Review on Advancement in Analytical Strategies for the Quantification of Clinically Relevant Biological Transporters.

Success of a drug discovery program is highly dependent on rapid scientific advancement and periodic inclusion of sensitive and specific analytical techniques. Biological membrane transporters can significantly alter the bioavailability of a molecule in its actual site of action. Expression of transporter proteins responsible for drug transport is extremely low in the biological system. Therefore, proper scientific planning in selection of their quantitative analytical technique is essential. This article discusses critical advancement in the analytical strategies for quantification of clinically relevant biological transporters for the drugs. Article cross-talked key planning and execution strategies concerning analytical quantification of the transporters during drug discovery programs.

Cancer targeting potential of some ligand-anchored poly(propylene imine) dendrimers: a comparison.

The present investigation was aimed at developing and comparing the cancer-targeting potential of ligand-anchored dendrimers. Folate-, dextran-, and galactose-anchored poly(propylene imine) dendrimers were synthesized and characterized. Dendritic formulations were evaluated for ex vivo cytotoxicity on HeLa and SiHa cell lines. Flow cytometry studies were performed on the HeLa cell line. An ex vivo MTT assay on HeLa cells indicated IC(50) values of 0.05, 0.2, 0.8, and 0.08 µM for folate, dextran, and galactose formulations, and for free paclitaxel (PTX), respectively. An analogous observation was carried out in SiHa cells, where IC(50) values of 0.6, 0.8, 10, and 6 µM were observed by folate, dextran, and galactose formulations, and free PTX, respectively. The outcome of the MTT assay and flow cytometry suggested the order of targeting potential of various ligands under investigation as folate > dextran > galactose. The outcome is deemed to be of scientific value and is believed to assist drug delivery scientists during selection of targeting ligands. FROM THE CLINICAL EDITOR: The cancer targeting potential of folate, dextran and galactose functionalized polypropyleneimine (PPI) dendrimers was studied by this group of investigators, reporting the order of targeting potential as folate > dextran > galactose.

Engineered nanoplex mediated targeted miRNA delivery to rescue dying podocytes in diabetic nephropathy.

MicroRNAs (miRNA) is vital for gene expression regulation and normal kidney function. Mainly, miRNA-30a is responsible for the homeostasis of podocytes. In the diabetic nephropathic condition, miRNA-30a is directly and primarily suppressed by hyperglycemic kidney induced Notch signaling pathway leads to podocyte damage and apoptosis. Thus, transferring the exogenous miRNA-30a to podocytes might improve albuminuria as well as podocytes injury. The deprived stability, poor targetability, and low specificity in vivo are critical limitations to attain this objective. This investigation reports the specific and efficient delivery of miRNA-30a mimic via cyclo(RGDfC)-gated polymeric-nanoplexes with dendrimer templates to alleviate podocyte conditions. The nanoplexes able to protect RNase enzyme and to exhibit greater cellular uptake viaαvß3 receptor selective binding in HG treated podocytes. The nanoplexes up-regulated the expression level of miRNA-30a and repress the elevated Notch-1 signaling in HG exposed podocytes. The critical results of in vivo experimentation attribute marked suppression of Notch-1 in streptozotocin (STZ) induced diabetic C57BL/6 mice and reduced glomerular expansion and fibrosis in the glomerular area. Developed nanoplexes represents an efficient platform for the targeted delivery of exogenous miRNA to podocytes. The approach developed herein could be extrapolated to other gene therapeutics and other kidney-related diseases.

Multifunctional polymeric micellar nanomedicine in the diagnosis and treatment of cancer.

Polymeric micelles are a prevalent topic of research for the past decade, especially concerning their fitting ability to deliver drug and diagnostic agents. This delivery system offers outstanding advantages, such as biocompatibility, high loading efficiency, water-solubility, and good stability in biological fluids, to name a few. The multifunctional polymeric micellar architect offers the added capability to adapt its surface to meet the looked-for clinical needs. This review cross-talks the recent reports, proof-of-concept studies, patents, and clinical trials that utilize polymeric micellar family architectures concerning cancer targeted delivery of anticancer drugs, gene therapeutics, and diagnostic agents. The manuscript also expounds on the underlying opportunities, allied challenges, and ways to resolve their bench-to-bedside translation for allied clinical applications.

Advancements in practical and scientific bioanalytical approaches to metabolism studies in drug development.

Advancement in metabolism profiling approaches and bioanalytical techniques has been revolutionized over the last two decades. Different in vitro and in vivo approaches along with advanced bioanalytical techniques are enabling the accurate qualitative and quantitative analysis of metabolites. This review summarizes various modern in vitro and in vivo approaches for executing metabolism studies with special emphasis on the recent advancement in the field. Advanced bioanalytical techniques, which can be employed in metabolism studies, have been discussed suggesting their particular application based on specific study objectives. This article can efficiently guide the researchers to scientifically plan metabolism studies and their bioanalysis during drug development programs taking advantage of a detailed understanding of instances of failure in the past.

Artificial intelligence in drug discovery and development.

Artificial intelligence-integrated drug discovery and development has accelerated the growth of the pharmaceutical sector, leading to a revolutionary change in the pharma industry. Here, we discuss areas of integration, tools, and techniques utilized in enforcing AI, ongoing challenges, and ways to overcome them.

Nanomedicines accessible in the market for clinical interventions.

Nanomedicines refers to nanotechnology inspired pharmaceutical products often referred to as 'nanopharmaceuticals.' It has displayed commendable potential in enhancing therapeutic efficacy as well as in reducing the side effects associated with conventional drug counterpart. Recent years have monitored the entry of a large amount of nanomedicine in the market with an appreciable market share to date. Despite this, the development of nanomedicine is posing challenges (i.e., safety, regulatory hurdles, cost, scale-up issues, etc.) that need to be resolved for their market entry. This review presents a cross-sectional discussion on the nanomedicine-derived products available in the market for both clinical and diagnostic applications. An overview of its market potential, market size, and the products that are currently in the clinical stages is also provided. The review also expounds on the challenges faced by nano-drug products at the time of their commercialization.