Harshita Singhai

Aim: A hypoxia-responsive drug-loaded liposomal drug delivery system was designed with the aim of effective treatment of breast cancer. This involves the synthesis and characterization of a nitroimidazole derivative incorporated within the optimized nanoprobe co-loaded with berberine and doxorubicin. Background: Breast cancer is a major global health burden, demanding innovative therapeutic strategies to improve treatment modalities with minimal adverse effects. Although conventional chemotherapy is effective to some extent, it remains constrained by limited specificity, systemic toxicity, and undesirable side effects. These limitations can be addressed by spatiotemporal targeted drug delivery with minimal contact with healthy cells. Purpose. Objective: The key objective of this study is to design a delivery system releasing the drug only in response to nitroreductase enzymes overexpressed in an altered hypoxic tumor microenvironment. This favors targeted drug release, tailoring breast cancer treatment. Methods: The nitroimidazole derivative was synthesized by a one-step nucleophilic substitution reaction, which was further characterized by FTIR and 1H NMR spectroscopy. The liposomal formulations consisting of plain, PEGylated, and hypoxia-responsive liposomes were optimized using a Box-Behnken design with the aim of achieving the desired vesicle size and entrapment efficiency of berberine and doxorubicin. The liposomal formulations were prepared using DPPC, DMPC, DSPE-PEG2000, and cholesterol, which were further characterized by physicochemical evaluation. In addition, sodium dithionite was used to evaluate the hypoxia-responsive structural distortion releasing the drug. The formulations were further assessed for hemolytic toxicity and cytotoxicity assays against MDA-MB-231 breast cancer cells. Results: The hypoxia-responsive derivative was successfully synthesized and characterized, affirming its suitability for the desired response. Liposomal formulations incorporating this nitroimidazole derivative met the desired standards, demonstrating optimal physicochemical characteristics. Notably, hypoxia-triggered drug release demonstrated a significant burst release under an induced hypoxic tumor microenvironment, with minimal hemolytic toxicity and superior cytotoxicity against the MDA-MB-231 breast cancer cell line compared to free drugs and other prepared liposomal formulations. Conclusion: These findings suggest that hypoxia-responsive co-loaded liposomal drug delivery systems offer a promising approach for targeted therapy, enhancing efficacy with reduced systemic side effects.

This descriptive review comprehensively examines recent advances in the genetic improvement of medicinal plants through the application of CRISPR-Cas9 genome-editing technology, highlighting its transformative potential in biotechnology and pharmacognosy. The review systematically discusses the fundamental principles of the CRISPR-Cas9 system, including its mechanism of action, delivery strategies, and comparative advantages over conventional genome-editing techniques. Particular emphasis is placed on the genetic enhancement of medicinal plant species to improve the qualitative and quantitative production of bioactive secondary metabolites through targeted modification of key genetic traits. In addition, the review explores the application of CRISPR-Cas9 for enhancing stress tolerance, environmental adaptability, and the regulation of metabolic biosynthetic pathways. Representative case studies involving medicinal plant species, including Artemisia annua and Catharanthus roseus, are critically evaluated to demonstrate the successful implementation of CRISPR-Cas9-mediated genome editing. Furthermore, the review discusses the synergistic integration of metabolic engineering, omics technologies, and synthetic biology for optimizing secondary metabolite biosynthesis. Finally, it highlights the growing role of next-generation genome-editing technologies, particularly CRISPR-Cas9, in advancing sustainable phytopharmaceutical and nutraceutical research and facilitating the development of high-value medicinal plant resources.

Ocular disorders such as age-related macular degeneration, cataract, dry eye disease, and diabetic retinopathy represent a growing global public health burden. Natural bioactive compounds, particularly carotenoids, flavonoids, and traditional herbal extracts, have demonstrated significant antioxidant, antiinflammatory, and neuroprotective effects on ocular tissues. However, the clinical translation of these phytomolecules is often limited by poor solubility, low stability, and inadequate ocular bioavailability. Recent advances in nanotechnology have enabled the development of targeted delivery platforms, including nanoparticles, nanoemulsions, hydrogels, and liposomes, which enhance tissue-specific delivery, bioavailability, and therapeutic efficacy. This review critically evaluates current evidence from in vitro, in vivo, and clinical studies on the role of natural compounds in ocular health, highlighting their mechanisms of action, safety profiles, and pharmacological potential. Furthermore, the integration of traditional medicinal systems with modern ophthalmic strategies, supported by personalised nanoformulation approaches, offers promising avenues for holistic and patient-centred eye care. Key challenges related to standardisation, regulatory compliance, quality control, and large-scale manufacturing are discussed, along with future directions for bioprospecting novel ocular bioactives and advancing integrative strategies for sustainable eye health management.

Candida albicans remains a major clinical threat because of its highly invasive nature, affecting mucosal surfaces and superficial tissues and possessing the ability to progress to life-threatening systemic infections, particularly in immunocompromised individuals. The extensive use of conventional antifungal agents has contributed to the emergence of antifungal resistance and dose-limiting toxicity, highlighting the need for alternative therapeutic strategies. Recent studies have demonstrated that combining plant-derived phytoconstituents with conventional antifungal drugs enhances therapeutic efficacy against C. albicans while reducing the development of antifungal resistance. This review explores the synergistic interactions between phytochemicals and standard antifungal agents, emphasizing their mechanistic roles in potentiating the activity of azoles, polyenes, and echinocandins through multi-targeted mechanisms. These mechanisms include disruption of fungal cell membrane integrity, inhibition of drug efflux pumps, induction of mitochondrial dysfunction, and generation of oxidative stress. Collectively, these effects impair fungal virulence, inhibit biofilm formation, enhance antifungal susceptibility, and improve treatment outcomes. Furthermore, such combinatorial approaches permit dose reduction of conventional antifungal agents, thereby minimizing drug-associated toxicity and slowing the emergence and progression of antifungal resistance.

The growing global burden of cardiovascular diseases necessitates the exploration of novel and complementary therapeutic strategies. Hawthorn (Crataegus spp.), a traditional herbal medicine, has gained considerable attention for its potential cardioprotective properties. This review provides a comprehensive overview of the botanical profile, phytochemical composition, and pharmacological activities of hawthorn, highlighting its role as a naturally derived cardiotonic agent. The therapeutic effects of hawthorn are primarily attributed to its bioactive constituents, particularly flavonoids and oligomeric proanthocyanidins, which exhibit vasodilatory, antioxidant, mild positive inotropic, and antiarrhythmic properties. Evidence from preclinical studies and selected clinical investigations suggests that hawthorn may support cardiovascular function, including improvements in exercise tolerance, endothelial function, and symptom management in conditions such as mild-tomoderate heart failure, hypertension, and angina. However, it is important to note that the current evidence is largely derived from secondary sources, including preclinical data and limited clinical trials, and does not establish hawthorn as a curative or standalone therapy. Compared with synthetic cardiotonic agents, hawthorn demonstrates a favorable safety profile, though variability in extract composition and dosing remains a significant limitation. Overall, while hawthorn shows promise as an adjunctive therapy in cardiovascular disease management, further well-designed, large-scale clinical studies and standardized formulations are required to validate its efficacy, clarify mechanisms of action, and support its integration into evidence-based clinical practice.

Bone regeneration remains a major clinical challenge due to the limited bioactivity, high cost, and adverse effects associated with current grafts and synthetic therapeutics. Herbal phytometabolites, including flavonoids, alkaloids, and terpenoids, have emerged as promising multitarget agents capable of modulating key pathways involved in skeletal repair. These natural compounds exert osteoinductive effects by activating Runx2/Osterix and stimulating BMP2/Smad and Wnt/β- catenin signaling; reducing bone resorption through RANKL/OPG regulation and NFATc1/NF-κB suppression; enhancing angiogenesis via VEGF upregulation and HIF-1α stabilization; and supporting osteoconduction by promoting collagen synthesis and alkaline phosphatase-mediated mineralization. This review systematically evaluates the structural diversity, biological mechanisms, and therapeutic potential of phytochemicals in bone healing, along with advancements in their delivery through polymeric nanoparticles/microspheres, bioactive glass and calcium phosphate scaffolds, thermosensitive hydrogels, functionalized implants, and emerging stimuli-responsive and 3D/4Dprinted biomaterials. By integrating traditional botanical knowledge with modern biomaterial engineering, we provide a comprehensive translational framework for developing phytochemical-based bone therapeutics as cost-effective, biocompatible alternatives to recombinant growth factors in the expanding global bone graft market.

Breast cancer (BC) remains a significant global health challenge, with existing treatments often accompanied by severe side effects and high recurrence rates. This review explores the potential of natural products as complementary therapies for breast cancer management, highlighting their bioactive compounds' diverse therapeutic effects, including antioxidant, anti-inflammatory, and apoptosis-inducing properties. Key classes of natural compounds, such as polyphenols (green tea, curcumin, resveratrol), flavonoids (quercetin, genistein), terpenoids (limonene, lycopene), and alkaloids (berberine, vincristine), are discussed for their anticancer efficacy. These natural agents have demonstrated a promising preclinical efficacy with the ability to inhibit tumor growth, modulating cell signalling pathways, and enhancing conventional cancer treatment modalities. Additionally, the review covers dietary sources rich in these bioactives, including fruits, vegetables, and herbs, as well as supplements, which offer practical ways to incorporate these compounds into cancer prevention and treatment strategies. While preclinical studies and clinical trials show promising results, challenges such as bioavailability, standardization, and regulatory approval remain obstacles to the clinical use of natural products. Future research focuses on overcoming these limitations by integrating the natural products in breast cancer management. This review underscores the potential of natural products to contribute significantly to innovative and less toxic approaches to breast cancer treatment and prevention.

Polymers of natural origin have garnered significant attention in pharmaceutical sciences due to their eco-friendly, biocompatible, and sustainable nature. This review explores the diverse applications of natural polymers, focusing on their roles as excipients in drug formulation and delivery. Derived from plant, animal, and protein sources, these polymers are instrumental in designing novel drug delivery systems such as controlled, sustained, and targeted therapies. The review highlights the properties of natural polymers, including biodegradability, biocompatibility, and cost-effectiveness, while also addressing challenges like variability in chemical composition and microbial contamination. Recent advancements in polymeric innovations, such as hydrogel and nanoparticle-based systems, are discussed for their potential in enhancing drug stability, solubility, and bioavailability. The applications extend to wound healing, tissue engineering, and regenerative medicine, where these polymers mimic biological environments to promote cellular growth and repair. Additionally, the review sheds light on emerging polymers, including Moringa seed mucilage and fenugreek gum, as promising candidates for pharmaceutical innovation. By bridging the gap between natural resource utilization and modern therapeutic needs, this work underscores the critical role of herbal polymers in advancing sustainable and effective pharmaceutical solutions.

The increasing global burden of antimicrobial resistance (AMR) has stimulated renewed interest in plant-derived phytochemicals and polyherbal formulations as potential adjuncts to conventional antimicrobial therapy. This article presents a narrative review, supported by a structured literature search, that synthesizes mechanistic and translational evidence on plant-based strategies targeting resistant bacterial pathogens. Literature was identified through searches of major scientific databases, including PubMed, Scopus, and Web of Science, with emphasis on studies published over the past two decades. Evidence is critically organised according to experimental level, distinguishing in vitro findings, in vivo observations, and available clinical data. Plant-derived compounds, including alkaloids, flavonoids, terpenoids, phenolics, and saponins, exhibit diverse antimicrobial and antibiofilm activities. Reported mechanisms include membrane disruption, inhibition of quorum sensing and biofilm formation, interference with nucleic acid and protein synthesis, modulation of efflux pumps, and attenuation of resistance-associated pathways. While reproducible antibacterial activity is frequently observed under laboratory conditions, animal studies remain limited, and robust clinical trials are scarce. Polyherbal formulations derived from traditional medical systems propose multi-target synergistic effects; however, pharmacodynamic validation and dose standardization remain insufficient. Key translational challenges include variability in extract composition, incomplete pharmacokinetic and pharmacodynamic characterization, limited bioavailability, potential toxicity, and clinically relevant herb–drug interactions. Many antimicrobial effects reported in vitro occur at concentrations that have not yet been demonstrated to be achievable or safe in humans. Emerging approaches such as nano-enabled delivery systems and omics-guided phytochemical characterisation may improve therapeutic precision but require rigorous validation. Overall, plant-derived products are best positioned as adjunctive resistance-modifying strategies rather than replacements for conventional antibiotics, pending standardised development and high-quality clinical evaluation.

Lipid-Polymer Hybrid Nanoparticles (LPHNPs) have emerged as a revolutionary drug delivery platform in oncology, addressing critical challenges such as poor drug bioavailability, nonspecific distribution, and systemic toxicity. These hybrid systems combine the complementary advantages of polymeric nanoparticles and liposomes, offering improved biocompatibility, high drugloading capacity, and precise tumor targeting. Their unique structural composition facilitates controlled drug release and enhanced stability, enabling sustained therapeutic effects. This review focuses on the characteristics, synthesis methods, and tumor-targeting mechanisms of LPHNPs, highlighting their pivotal role in advancing solid tumor drug delivery. Various preparation techniques, including traditional two-step, modified two-step, and single-step approaches, are discussed to elucidate their contributions to nanoparticle formulation and optimization. LPHNPs employ both passive and active targeting strategies, capitalizing on tumor microenvironment-specific factors, such as pH, enzymes, and temperature, for passive targeting, and leveraging specific ligands, such as folate, antibodies, and aptamers, for active targeting. These mechanisms enhance therapeutic precision and minimize off-target effects, significantly improving treatment outcomes. With advancements in emerging nanotechnologies, LPHNPs demonstrate immense potential as next-generation drug delivery systems, providing solutions to longstanding challenges in cancer therapy. They offer a promising path toward more effective, safe, and patient-specific treatments for solid tumors. This review provides a comprehensive overview of LPHNPs, highlighting their current applications and future prospects for transforming cancer therapeutics.