A new insight into the Huisgen reaction: Heterogeneous Copper catalyzed azide-alkyne cycloaddition for the synthesis of 1,4-disubstitutedtriazole (from 2018-2023).

The Huisgen cycloaddition, often referred to as 1,3-Dipolar cycloaddition, is a well-established method for synthesizing 1,4-disubstituted triazoles. Originally conducted under thermal conditions [3+2] cycloaddition reactions were limited by temperature, prolonged reaction time, and regioselectivity. The copper catalyzed azide-alkyne cycloaddition (CuAAC) has emerged as a prominent method for producing 1,2,3-triazole with excellent yields and exceptional regioselectivity. Copper catalysts conventionally facilitate azide-alkyne cycloadditions, but challenges include instability and recycling issues. In recent years, there has been a growing demand for heterogeneous catalysts in various chemical reactions. The present review covers recent advancements from year 2018 to 2023 in the field of click reactions for obtaining 1,2,3-triazoles through Cu catalyzed 1,3-dipolar azide-alkyne cycloaddition and the properties of the catalyst, reaction conditions such as solvent, temperature, reaction time, and the impact of different heterogeneous copper catalysts on product yield.

Guanidinium-based Integrated Peptide Dendrimers: Pioneer Nanocarrier in Cancer Therapy.

The landscape of cancer therapy has witnessed a paradigm shift with the emergence of innovative delivery systems, and Guanidinium-based Peptide Dendrimers have emerged as a vanguard in this transformative journey. With their unique molecular architecture and intrinsic biocompatibility, these dendrimers offer a promising avenue for the targeted delivery of therapeutic cargo in cancer treatment. This comprehensive review delves into the intricate world of Guanidinium- based Peptide Dendrimers, unraveling their structural intricacies, mechanisms of action, and advancements that have propelled them from laboratory curiosities to potential clinical champions. Exploiting the potent properties of guanidinium, these dendrimers exhibit unparalleled precision in encapsulating and transporting diverse cargo molecules, ranging from conventional chemotherapeutics to cutting-edge nucleic acids. The review navigates the depths of their design principles, investigating their prowess in traversing the complex terrain of cellular barriers for optimal cargo delivery. Moreover, it delves into emerging trends, such as personalized therapeutic approaches, multimodal imaging, and bioinformatics-driven design, highlighting their potential to redefine the future of cancer therapy. Crucially, the review addresses the pivotal concerns of biocompatibility and safety, examining cytotoxicity profiles, immune responses, and in vivo studies. It underscores the importance of aligning scientific marvels with the stringent demands of clinical applications. Through each section, the narrative underscores the promises and possibilities that Guanidinium-based Peptide Dendrimers hold and how they can potentially reshape the landscape of precision cancer therapy.

Aptamer as a targeted approach towards treatment of breast cancer.

Aptamers, a novel type of targeted ligand used in drug delivery, have quickly gained popularity due to their high target specificity and affinity. Different aptamer-mediated drug delivery systems, such as aptamer-drug conjugate (ApDC), aptamer-siRNA, and aptamer-functionalised nanoparticle systems, are currently being developed for the successful treatment of cancer based on the excellent properties of aptamers. These systems can decrease potential toxicity and enhance therapeutic efficacy by targeting the drug moiety. In this review, we provide an overview of recent developments in aptamer-mediated delivery systems for cancer therapy, specifically for breast cancer, and talk about the potential applications and current issues of novel aptamer-based techniques. This study in aptamer technology for breast cancer therapy highlights key aptamers targeting well-established biomarkers such as HER2, oestrogen receptor, and progesterone receptor. Additionally, we explore the potential of aptamers in overcoming various challenges such as drug resistance and improving the delivery of therapeutic agents. This review aims to provide a deeper understanding of the present aptamer-based targeted delivery applications through in-depth analysis to increase efficacy and create new therapeutic approaches that may ultimately lead to better treatment outcomes for cancer patients.

Nanoparticles toxicity: an overview of its mechanism and plausible mitigation strategies.

Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.

An Expedition on Synthetic Methodology of FDA-approved Anticancer Drugs (2018-2021).

New drugs being established in the market every year produce specified structures for selective biological targeting. With medicinal insights into molecular recognition, these begot molecules open new rooms for designing potential new drug molecules. In this review, we report the compilation and analysis of a total of 56 drugs including 33 organic small molecules (Mobocertinib, Infigratinib, Sotorasib, Trilaciclib, Umbralisib, Tepotinib, Relugolix, Pralsetinib, Decitabine, Ripretinib, Selpercatinib, Capmatinib, Pemigatinib, Tucatinib, Selumetinib, Tazemetostat, Avapritinib, Zanubrutinib, Entrectinib, Pexidartinib, Darolutamide, Selinexor, Alpelisib, Erdafitinib, Gilteritinib, Larotrectinib, Glasdegib, Lorlatinib, Talazoparib, Dacomitinib, Duvelisib, Ivosidenib, Apalutamide), 6 metal complexes (Edotreotide Gallium Ga-68, fluoroestradiol F-18, Cu 64 dotatate, Gallium 68 PSMA-11, Piflufolastat F-18, 177Lu (lutetium)), 16 macromolecules as monoclonal antibody conjugates (Brentuximabvedotin, Amivantamab-vmjw, Loncastuximabtesirine, Dostarlimab, Margetuximab, Naxitamab, Belantamabmafodotin, Tafasitamab, Inebilizumab, SacituzumabGovitecan, Isatuximab, Trastuzumab, Enfortumabvedotin, Polatuzumab, Cemiplimab, Mogamulizumab) and 1 peptide enzyme (Erwiniachrysanthemi-derived asparaginase) approved by the U.S. FDA between 2018 to 2021. These drugs act as anticancer agents against various cancer types, especially non-small cell lung, lymphoma, breast, prostate, multiple myeloma, neuroendocrine tumor, cervical, bladder, cholangiocarcinoma, myeloid leukemia, gastrointestinal, neuroblastoma, thyroid, epithelioid and cutaneous squamous cell carcinoma. The review comprises the key structural features, approval times, target selectivity, mechanisms of action, therapeutic indication, formulations, and possible synthetic approaches of these approved drugs. These crucial details will benefit the scientific community for futuristic new developments in this arena.

A Complete Sojourn of Current Trends in Gastro-retentive Drug Delivery System: Recent Advances and Patent Survey.

The current work aims to provide a complete sojourn on gastro-retentive drug delivery system (GRDDS) along with formulation methods, polymer selection, and in vitro/ in vivo challenges with finished dosage forms. Ideally, a biopharmaceutical-hindered drug has a rapid clearance and erratic bioavailability due to its low aqueous solubility and permeability. Additionally, it also suffers from high first-pass metabolism and pre-systemic gut wall clearance. Gastro-retentive drug delivery systems have become an emerging technology where newer methodologies and scientific approaches have been used to provide the controlled release of drugs and provide a protective mechanism in the stomach. By the virtue of utilizing GRDDS as a dosage form, these formulations increase Gastroretention time (GRT) which prolongs the controlled release of the drug in the dosage form. GRDDS contribute to increased drug bioavailability and targeting at a site of action, which enhances therapeutic action and offers significant patient compliance. Furthermore, the present work also highlighted the critical role of polymers in favoring drug retention across GIT with the mechanism of gastro-retention and recommended concentration ranges. The emerging technology is also highlighted by the approved drug products and patented formulations in the recent decade which is depicted in a justified manner. GRDDS formulations have demonstrated clinical efficacy, which is supported by a compilation of patents for cutting-edge innovations in dosage forms that can be held in the stomach for an extended period of time.

Hydroxamic acid derivatives as selective HDAC3 inhibitors: computer-aided drug design strategies.

Histone deacetylases (HDACs) are critical epigenetic drug targets that have gained significant attention in the scientific community for the treatment of cancer. The currently marketed HDAC inhibitors lack selectivity for the various HDAC isoenzymes. Here, we describe our protocol for the discovery of novel potential hydroxamic acid based HDAC3 inhibitors through pharmacophore modeling, virtual screening, docking, molecular dynamics (MD) simulation and toxicity studies. The ten pharmacophore hypotheses were established, and their reliability was validated by different ROC (receiving operator curve) analysis. Among them, the best model (Hypothesis 9 or RRRA) was employed for searching SCHEMBL, ZINC and MolPort database to screen out hit molecules as selective HDAC3 inhibitors, followed by different docking stages. MD simulation (50 ns) and MMGBSA study were performed to study the stability of ligand binding modes and with the help of trajectory analysis, to calculate the ligand-receptor complex RMSD (root-mean-square deviation), RMSF (root-mean-square fluctuation) and H-bond distance, etc. Finally, in-silico toxicity studies were performed on top screened molecules and compared with reference drug SAHA and established structure-activity relationship (SAR). The results indicated that compound 31, with high inhibitory potency and less toxicity (probability value 0.418), is suitable for further experimental analysis.Communicated by Ramaswamy H. Sarma.

Pharmacophore modeling and virtual screening were performed with hydroxamic acid derivatives as HDAC3 inhibitors.MD simulation was performed for 50 ns time duration for selected protein-ligand complexes.SAR and toxicity studies (using TOPKAT tool) were performed.The results of these studies might be valuable in the further design and development of more potent HDAC3 inhibitors.

NOTCH Signaling Pathway: Occurrence, Mechanism, and NOTCH-Directed Therapy for the Management of Cancer.

It is now well understood that many signaling pathways are vital in carrying out and controlling essential pro-survival and pro-growth cellular functions. The NOTCH signaling pathway, a highly conserved evolutionary signaling pathway, has been thoroughly studied since the discovery of NOTCH phenotypes about 100 years ago in Drosophila melanogaster. Abnormal NOTCH signaling has been linked to the pathophysiology of several diseases, notably cancer. In tumorigenesis, NOTCH plays the role of a "double-edged sword," that is, it may act as an oncogene or as a tumor suppressor gene depending on the nature of the context. However, its involvement in several cancers and inhibition of the same provides targeted therapy for the management of cancer. The use of gamma (γ)-secretase inhibitors and monoclonal antibodies for cancer treatment involved NOTCH receptors inhibition, leading to the possibility of a targeted approach for cancer treatment. Likewise, several natural compounds, including curcumin, resveratrol, diallyl sulfide, and genistein, also play a dynamic role in the management of cancer by inhibition of NOTCH receptors. This review outlines the functions and structure of NOTCH receptors and their associated ligands with the mechanism of the signaling pathway. In addition, it also emphasizes the role of NOTCH-targeted nanomedicine in various cancer treatment strategies.

Quality by design-assisted development of D-α-tocopherol polyethylene glycol 1000 succinate-incorporated gefitinib-loaded cationic liposome(s).

Aim: Gefitinib-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes (GEF-TPGS-LIPO+) were developed and optimized by the quality by design (QbD) approach for its potential anticancer effect. Methods/materials: Box-Behnken design (BBD) a systematic design of experiments was added to screen and optimize the formulation variables. Results: GEF-TPGS-LIPO+ shows vesicle size (210 ± 4.82 nm), polydispersity index (0.271 ± 0.002), zeta potential (22.2 ± 0.84 mV) and entrapment efficiency (82.3 ± 1.95). MTT result shows the enhanced cytotoxicity and higher intracellular drug uptake with highest and lowest levels of the reactive oxygen species and NF-κB expressions on A549 lung cancer cells, determined by fluorescence-activated cell sorting flow cytometry. Conclusion: Potential anticancer effect on A549 cells might be found due to cationic liposomal interaction with cancer cells.

α-Tocopherol Polyethylene Glycol 1000 Succinate-Based Cationic Liposome for the Intracellular Delivery of Doxorubicin in MDA-MB-231 Triple-Negative Breast Cancer Cell Line.

Present research work reports the development of doxorubicin (DOX) loaded α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes. The developed formulation was evaluated for its anticancer potential and intracellular uptake against the MDA-MB-231 breast cancer cell line. Moreover, hemocompatibility studies were also done on human blood red blood cells for the determination of blood compatibility. The prepared doxorubicin-loaded TPGS liposomes (DOX-LIPO-TPGS) and doxorubicin-loaded cationic liposomes (DOX-LIPO+-TPGS) reveal vesicle size (177.5 ± 2.5 and 201.7 ± 2.3 nm), polydispersity index (0.189 ± 0.01 and 0.218 ± 0.02), zeta potential (-36.9 ± 0.7 and 42 ± 0.9 mv), and % entrapment efficiency (65.88% ± 3.7% and 74.5% ± 3.9%). Furthermore, in vitro, drug release kinetics of the drug alone and drug from formulation shows sustained release behavior of developed formulation with 99.98% in 12 h and 80.98% release of the drug in 72 h, respectively. In addition, cytotoxicity studies and cellular DOX uptake on the MDA-MB-231 breast cancer cell line depict higher cytotoxic and drug uptake potential with better hemocompatibility of DOX-LIPO+-TPGS with respect to DOX. The data from the study revealed that TPGS plays an important role in enhancing the formulation's quality attributes like stability, drug release, cytotoxicity, and hemocompatibility behavior. This may serve that TPGS-coated cationic liposome as a vital candidate for the treatment of cancer and drug delivery in case of breast cancer.

Development and Method Validation of Design of Experiments-Optimized Tablet Formulation for Simultaneous Detection of Exemestane and Everolimus.

The development and analysis of pharmaceutical formulations often involves the determination of multiple active ingredients in a dosage form. The aim of the present study is to develop a convenient method for simultaneous estimation of Exemestane (EXE) and Everolimus (EVE) in bulk and in systemically designed tablet dosage form. Methanol was used as a solvent for developing linear curves and validated in terms of various parameters, such as selectivity, sensitivity, linearity, precision, accuracy, and robustness. Method validation observed that the proposed method is reliable and reproducible, meeting the regulatory requirements for pharmaceutical analysis with a relative standard deviation of <2%. The developed method was found to be sensitive and selective in simultaneous equation method. The unknown concentrations of EVE and EXE were found to be 10.431 and 10.232, respectively. The next step is to systematically design a tablet formulation for EXE and EVE containing ß-cyclodextrin as a polymer. Microcrystalline cellulose (X1), sodium starch glycolate (X2), and beta-cyclodextrin (X3) are the critical variables and hardness (Y2) and friability (Y3) were selected as prime responses. Analysis of variance provides significance of the model, and the predicted batch gives a high desirability value of 0.862. In vitro dissolution profiles of optimized batch (OB1) were signified by high drug release profile as 89.47% and 96.00% for EVE and EXE in tablet formulation, as compared with pure API, respectively. This study signifies enhancement in biopharmaceutical attributes of EXE and EVE in tablet formulation and robust simultaneous estimation by the UV method. In a nutshell, this study provides the simultaneous estimation method in tablet dosage form, and further research is crucial for the advancement of pharmaceutical analysis and the formulation of effective medicines.

Multifunctional nanotherapeutics for intracellular trafficking of doxorubicin against breast cancer.

Aims: To develop an estrone-targeted d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based liposomal system for enhanced intracellular delivery of doxorubicin (DOX). Materials & methods: Zetasizer, transmission electron microscopy, energy dispersive x-ray, Fourier-transform infrared spectroscopy, differential scanning calorimetry, x-ray diffraction, confocal laser scanning microscopy and FACS analysis were used for formulation characterization and evaluation. Results: The DOX-LIPO-TPGS and DOX-LIPO-TPGS-estrone formulations had vesicle sizes (117.6 ± 3.51; 144 ± 5.00 nm), zeta potential (-36.4 ± 0.75; -35.8 ± 0.76), polydispersity index (0.123 ± 0.005; 0.169 ± 0.005) and percent entrapment efficiency (73.56 ± 3.55; 77.16 ± 3.83%) with improved cytotoxicity and cellular uptake, confirming the targeted potential of the developed formulations. Conclusion: The results suggest that the developed liposomal formulation with desired characteristics is potentially capable of nonimmunogenic, site-specific drug delivery to targeted cancer sites and reduced DOX-associated cardiac toxicity.

Doxorubicin (DOX) is an effective chemotherapy drug to treat breast cancer. However, DOX can cause unwanted side effects such as damage to the heart. This is due to side effects in healthy body tissues. This study was designed to develop nanoparticles that target cancer cells specifically to improve the delivery of DOX to these cells and prevent side effects elsewhere. Nanoparticles called liposomes were used as the platform for delivering DOX. Liposomes are sometimes coated with d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS), a synthetic vitamin D derivative. This helps the liposome evade the immune system and release the drug more effectively. TPGS was tethered with estrone (ES), a type of estrogen. Certain breast cancer cells have many more estrogen receptors on their cell surface than healthy cells. TPGS-ES was coated on DOX-loaded liposomes to achieve enhanced intracellular delivery of DOX to breast cancer cells specifically. These liposomes were called DOX-LIPO-TPGS-ES. This liposome proved more toxic to cells in a breast cancer cell line than free DOX or liposomes without tethered ES. When tested in rats, DOX-LIPO-TPGS-ES showed increased tumor uptake compared with free DOX or liposomes without tethered ES. Rats treated with either liposomal drug showed normal levels of key markers associated with heart function, whereas those treated with free DOX showed increased levels of these markers. These results suggest that DOX-LIPO-TPGS-ES is capable of highly targeted delivery of DOX with limited side effects.

Emerging targeted therapeutic strategies for the treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC), a subtype of breast cancer that lacks expression of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), has clinical features including a high degree of invasiveness, an elevated risk of metastasis, tendency to relapse, and poor prognosis. It constitutes around 10-15% of all breast cancer, and having heredity of BRCA1 mutated breast cancer could be a reason for the occurrence of TNBC in women. Overexpression of cellular and molecular targets, i.e. CD44 receptor, EGFR receptor, Folate receptor, Transferrin receptor, VEGF receptor, and Androgen receptor, have emerged as promising targets for treating TNBC. Signalling pathways such as Notch signalling and PI3K/AKT/mTOR also play a significant role in carrying out and managing crucial pro-survival and pro-growth cellular processes that can be utilised for targeted therapy against triple-negative breast cancer. This review sheds light on various targeting strategies, including cellular and molecular targets, signalling pathways, poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors PARP, immunotherapy, ADCs have all found a place in the current TNBC therapeutic paradigm. The role of photothermal therapy (PTT) and photodynamic therapy (PDT) has also been explored briefly.

Recent advances in drug delivery approaches for rheumatoid arthritis.

Morbidity, disability, and healthcare expenses associated with rheumatoid arthritis (RA) impose a considerable health and economical burden on both patients and healthcare systems. This review aimed to examine the pathophysiological aspects of RA that may help design different types of drugs and drug delivery systems. These include monoclonal antibodies, immunoglobulins, tiny chemicals, and transgenes for gene therapy. These novel nanocarrier-based therapies target the underlying biological processes involved in RA while minimizing the systemic adverse effects of drugs.

A short appraisal of polylactic-co-glycolic acid based polymer nanotechnology for colon cancer: recent advances and literature evidences.

The currently available formulations provided non-targeted treatment of colon cancer, the deadliest cancer variant. Due to biopharmaceutical hindrances, the majority of the drugs are unable to reach the target site. Polylactic-co-glycolic acid (PLGA) is one of the versatile polymers in cancer treatment, diagnostics and theranostics. The unique mechanism of surface modifications in PLGA properties in colon cancer has been a keen interest to be used in different nanoparticles for improving biopharmaceutical attributes. The ongoing use of these smart nano-carriers has allowed targeted delivery of several active components on a wide scale. The main goal of this review is to compile information on PLGA-based nanocarriers which possess several desirable properties for drug delivery applications, including biocompatibility, biodegradability and tunable drug-release kinetics.

Recent advancements in novel formulations of anti-psoriatic agents for effective delivery: clinical importance and patent survey.

Objectives An autoimmune-mediated dermatological ailment featuring recurrent episodes is acknowledged as psoriasis. Around the world, 2-3% of people suffer from this autoimmune skin condition. The primary goal of the current review is to analyse and determine the effectiveness of conventional and emerging nano technological strategies to alleviate psoriasis and discuss future perspectives. Evidence acquisition A thorough search of numerous electronic databases, including Science Direct, Scopus, Google Scholar, Clinical Trials, Google Patents, Research Gate, and PubMed, yielded all the data used in this review paper about the management of psoriasis via various anti-psoriatic agent and nanotechnology approaches. Keywords such as topical, liposomes, niosomes, micro needles, clinical trials, patents, pathogenesis, biosimilars, cytokines, and other pertinent words were investigated. Results Nano technological approaches are gaining prominence since they enable targeted delivery, rapid onset of action with limited systemic exposure. Researchers have investigated innovative, alternative therapeutic approaches that are both secure and efficient for treating psoriatic conditions. Further, the potential role of numerous psoriatic conventional therapies has been explored. The patents granted or in process to address psoriasis via topical route have been well explored. Modern nanotechnology has made it possible for pharmaceuticals to be delivered with improved physical, chemical, pharmacokinetic, and pharmacodynamic qualities. Despite extensive research complete cure for psoriasis is hampered. Conclusion Relying on the extensive literature review, it can be inferred that nanoparticles based novel delivery strategies have the possibility of enhancing the pharmacological activity and eliminating or resolving problems associated with this ailment. The different drug delivery systems available for the treatment of psoriasis along with the clinical trials in different stages, patents in process and granted, the commercialized status of therapeutic molecules, and the future of research in this area have been thoroughly reviewed.

Recent Advances in Nanocarrier-based Approaches to Atopic Dermatitis and Emerging Trends in Drug Development and Design.

Atopic dermatitis (AD), commonly known as Eczema, is a non-communicable skin condition that tends to become chronic. The deteriorating immunological abnormalities are marked by mild to severe erythema, severe itching, and recurrent eczematous lesions. Different pharmacological approaches are used to treat AD. The problem with commercial topical preparations lies in the limitation of skin atrophy, systemic side effects, and burning sensation that decreases patient compliance. The carrier-based system promises to eliminate these shortcomings; thus, a novel approach to treating AD is required. Liposomes, microemulsions, solid lipid nanoparticles (SLNs), nanoemulsions, etc., have been developed recently to address this ailment. Despite extensive research in the development method and various techniques, it has been challenging to demonstrate the commercial feasibility of these carrier-based systems, which illustrates a gap among the different research areas. Further, different soft wares and other tools have proliferated among biochemists as part of a cooperative approach to drug discovery. It is crucial in designing, developing, and analyzing processes in the pharmaceutical industry and is widely used to reduce costs, accelerate the development of biologically innovative active ingredients, and shorten the development time. This review sheds light on the compilation of extensive efforts to combat this disease, the product development processes, commercial products along with patents in this regard, numerous options for each step of computer-aided drug design, including in silico pharmacokinetics, pharmacodynamics, and toxicity screening or predictions that are important in finding the drug-like compounds.

Advancement in Solubilization Approaches: A Step towards Bioavailability Enhancement of Poorly Soluble Drugs.

A drug's aqueous solubility is defined as the ability to dissolve in a particular solvent, and it is currently a major hurdle in bringing new drug molecules to the market. According to some estimates, up to 40% of commercialized products and 70-90% of drug candidates in the development stage are poorly soluble, which results in low bioavailability, diminished therapeutic effects, and dosage escalation. Because of this, solubility must be taken into consideration when developing and fabricating pharmaceutical products. To date, a number of approaches have been investigated to address the problem of poor solubility. This review article attempts to summarize several conventional methods utilized to increase the solubility of poorly soluble drugs. These methods include the principles of physical and chemical approaches such as particle size reduction, solid dispersion, supercritical fluid technology, cryogenic technology, inclusion complex formation techniques, and floating granules. It includes structural modification (i.e., prodrug, salt formation, co-crystallization, use of co-solvents, hydrotrophy, polymorphs, amorphous solid dispersions, and pH variation). Various nanotechnological approaches such as liposomes, nanoparticles, dendrimers, micelles, metal organic frameworks, nanogels, nanoemulsions, nanosuspension, carbon nanotubes, and so forth have also been widely investigated for solubility enhancement. All these approaches have brought forward the enhancement of the bioavailability of orally administered drugs by improving the solubility of poorly water-soluble drugs. However, the solubility issues have not been completely resolved, owing to several challenges associated with current approaches, such as reproducibility in large scale production. Considering that there is no universal approach for solving solubility issues, more research is needed to simplify the existing technologies, which could increase the number of commercially available products employing these techniques.