Poor pharmaceutical material properties of active pharmaceutical ingredients (APIs) can result in suboptimal manufacturing and therapeutic outcomes. Rivaroxaban (RIV) was explored as a model API due to its poor pharmaceutical properties and challenging industrial processability. In this research, crystal habit modification (CHM) of RIV was explored via solvent evaporation, cooling crystallization, and sonocrystallization methods. RIV (irregular) habit was modified to cuboidal, plate, and fiber via solvent evaporation; however, these were not further explored due to their large crystal sizes (>400 µm), which could pose serious dissolution and dose uniformity issues. Cooling crystallization method yielded plate (RIV_ACT) and blade-shaped (RIV_ACN) crystals with sizes < 200 µm. Further, CHM by sonocrystallization yielded tabular (RIV_SN6) crystals < 10 µm in size, which also exhibit a lower aspect ratio, a lower span value, and a narrower crystal size distribution than RIV_ACT and RIV_ACN. No polymorphic changes in modified habits were observed, as confirmed by PXRD, DSC, and TGA. Powder flowability improved significantly in the RIV_SN6 than in RIV_ACT and RIV_ACN (p < 0.0001) due to its narrow crystal size distribution. Interestingly, the RIV_SN6 showed improved tensile strength (p < 0.05) at a compression force of 300 MPa and exhibited improved wettability due to the exposure of polar functional groups on the modified habits. Furthermore, significant improvements in polar energy (p < 0.05) and ∼1.88 fold of IDR (p < 0.0001) were observed in RIV_SN6 compared to the RIV_ACT and RIV_ACN due to the prominence of polar groups and hydrophilic components on the particular facet.

Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited therapeutic options. In the present study, folic acid-functionalized nanostructured lipid carriers (FA-NLCs) co-loaded with docetaxel (DOC) and erlotinib (ERL) were evaluated for targeted combinatorial TNBC therapy. The optimized FA-DOC/ERL-NLCs demonstrated enhanced cellular uptake and significantly improved cytotoxicity compared with free drugs and non-targeted formulations. Mechanistic studies revealed increased reactive oxygen species generation, mitochondrial membrane depolarization, apoptosis induction, and inhibition of colony formation and cell migration, confirming enhanced anticancer efficacy. Pharmacokinetic studies demonstrated prolonged systemic circulation, sustained drug release, and improved bioavailability of NLC formulations. In vivo studies using 4T1 tumor-bearing mice showed significant tumor suppression with reduced systemic toxicity following treatment with FA-functionalized NLCs. Biochemical and histopathological analyses further confirmed improved safety and preservation of organ integrity compared with free drug treatments. Collectively, FA-functionalized NLCs represent a promising targeted nanocarrier platform for effective TNBC therapy.

INTRODUCTION:Proteolysis-targeting chimeras (PROTAC) are an innovative treatment approach that selectively breaks down disease-relevant proteins by utilizing the ubiquitin-proteasome system. Other than PROTAC, Molecular glue, Lysosome-Targeting Chimaera (LYTAC), GlueTAC, Autophagy-Targeting Chimaera (AUTAC), Autophagosome Tethering Compound (ATTEC), and Antibody-based PROTAC (AbTAC) are emerging targeted protein degradation (TPD) techniques, of which PROTAC offers several benefits. AREAS COVERED:This review discusses the development of proteolysis-targeting chimeras (PROTACs) for targeted protein degradation, highlighting their mechanism of action via the ubiquitin-proteasome system. It examines key physicochemical and pharmacokinetic challenges that limit clinical translation. Advanced formulation strategies, including nanoformulations and amorphous solid dispersions, prodrug improve solubility, bioavailability, and therapeutic efficacy. Additionally, characterization techniques are summarized, and the review outlines recent progress and critical considerations for the successful clinical translation of PROTAC-based therapeutics. Relevant articles from PubMed, Scopus, and Web of Science, spanning publications up to 2026, were gathered. EXPERT OPINION:PROTACs represent a transformative therapeutic modality, enabling selective protein degradation beyond conventional inhibition. Future research should focus on improving bioavailability, targeted delivery, and stability, while advancing prodrug strategies, E3 ubiquitin ligase selectivity, oral formulations, and predictive models for clinical translation. Additionally, it should emphasize scalable manufacturing, regulatory frameworks, and integration with emerging targeted protein degradation technologies.

ABSTRACT The integration of artificial intelligence (AI), and machine learning (ML) with nanomedicine represents a transformative approach in cancer drug delivery, offering solutions to long‐standing challenges such as formulation optimization, targeted delivery, and predictive efficacy. While nanocarriers like liposomes, dendrimers, and polymeric nanoparticles have enhanced site‐specific delivery, their development remains constrained by trial‐and‐error formulation methods. In this review, we critically examine how ML algorithms, including support vector machines, artificial neural networks, and deep learning models which are widely being applied to streamline nanoparticle design, predict drug release profiles, and personalize therapeutic regimens based on patient data. We highlight case studies where ML has accelerated nanoparticle fabrication, improved internalization modeling, and supported the development of self‐driving labs for formulation screening. We also discuss computational workflows, data handling strategies, and the operational principles behind commonly used ML models in pharmaceutical research. Importantly, the review addresses key limitations such as data scarcity, lack of model interpretability, and regulatory hurdles that hinder clinical translation. By synthesizing recent advances and identifying ongoing gaps, this article offers a roadmap for future interdisciplinary research at the interface of AI and nanomedicine.

Istradefylline (IDF), a selective adenosine A2A receptor antagonist, is used as adjunct therapy to manage motor fluctuations in Parkinson's disease. However, its clinical efficacy is limited by poor aqueous solubility, as it belongs to Biopharmaceutical Classification System (BCS) Class II. To overcome this limitation, IDF nanocrystals (IDF-NC) were developed using the nanoprecipitation technique with polyvinyl alcohol (PVA) as a stabilizer. Formulation parameters were initially screened using Plackett-Burman design and subsequently optimized via Box-Behnken design under Response Surface Methodology. The optimized IDF-NC demonstrated an average particle size of 185.33 +/- 20.85 nm, a polydispersity index of 0.212 +/- 0.050, and cuboidal morphology was confirmed by electron microscopic analysis. Thermal and structural characterization confirmed the preservation of crystallinity and absence of chemical interactions. In vitro drug release studies showed a similar to 6-fold increase in dissolution rate for IDF-NC compared to IDF. The nanocrystals were incorporated into a hydrogel base, which exhibited pseudoplastic behavior and suitable spreadability for transdermal application. Ex vivo permeation studies revealed that microneedling significantly enhanced drug permeation, achieving 62.16 +/- 1.73% permeation compared to 23.49 +/- 1.82% without microneedling. Overall, the combination of nanocrystal technology and microneedle-assisted delivery represents a promising strategy to enhance the transdermal bioavailability of poorly soluble drugs. These findings support further exploration through in vivo pharmacokinetic and pharmacodynamic evaluations.

Powder flowability of active pharmaceutical ingredients (APIs) plays a paramount role during tablet manufacturing as many APIs show poor flowability and compressibility. Coprocessing of drugs by quasi-emulsion solvent diffusion (QESD) process is an effective strategy to improve its powder flowability and compressibility. In this study, ethambutol hydrochloride (ETB), an anti-tubercular drug was coprocessed with hydroxypropyl methyl cellulose (HPMC) E15 at 2.5 % w/v concentration following the novel QESD methodology. Optimization of process parameters is an essential step before proceeding for scale-up batches. Hence, the effect of process parameters on the spherical agglomerates was explored by design of experiment (DoE) approach. Central composite design (CCD) was employed to study the effect of important process parameters on the quality attributes of the spherical agglomerates. Statistical analysis by standard least square method revealed that aqueous phase: organic phase (AP:OP) ratio and stirring rate had most significant impact (p < 0.05) on span, bulk density, circularity, and yield of the agglomerates. The powder flowability was predominantly dependent on the agglomerate circularity, followed by bulk density and span. It was found that powder samples with reduced circularity showed cohesive nature as indicated by Carr's index calculation. Spectral and thermal analysis of the agglomerates revealed no changes in the solid-state of ETB. Also, no changes were noticed in the dissolution profile of tablets prepared from the spherical agglomerates of different batches. The influence of QESD process parameters on the quality attributes of agglomerates were statistically evaluated and a desirability of 0.88 was obtained indicating good prediction accuracy.

ABSTRACT Persistent petroleum‐derived plastics have presented environmental problems, and this has amplified the world's interest in biodegradable and renewable alternatives. Bioplastic nanoparticles, as a novel class of materials with sustainability and improved performance, are among them. This review presents the main categories of bioplastics derived from natural, microbial, and chemically modified sources, highlighting their structural features and physicochemical properties. Special attention is paid to the role of nanotechnology in overcoming the drawbacks generally associated with traditional bioplastics, such as low mechanical strength, inadequate thermal stability, and barrier performance. Different fabrication strategies such as top‐down, bottom‐up, and green synthesis approaches and their impact on size, morphology, and functionality of nanoparticles are discussed. Moreover, the review also includes surface engineering and functionalization techniques that provide better stability, targeting, and response to external stimuli. The study discusses the degradability of bioplastics in composting, soil, and aqueous environment along with the processes involved in making bioplastics useful for lab and industrial scale manufacture. Moreover, the review also considers the fate of residual bioplastics under environmental conditions in which bioplastics may not completely degrade, pointing out the possible risks from ecotoxicology and drawbacks of biodegradable claims under natural environmental conditions. Specific focus is placed on issues related to the translation of technology into clinical and industrial setting. In addition, the increasing applications of bioplastic nanoparticles in drug delivery, gene therapy, vaccine systems, food packaging, agriculture, and environmental remediation are reviewed critically. While significant progress has been achieved, scalability, economic feasibility, safety assessment, and regulatory compliance still pose challenges to large‐scale implementation. Emerging developments in synthetic biology, artificial intelligence‐assisted formulation design, and evolving regulatory frameworks are discussed as key factors expected to influence the future advancement and commercialization of nanoengineered bioplastic systems. This review summarizes the paradigm shifting impact of nanoengineered bioplastics on sustainable material science and discusses future prospects for their safe and effective implementation in a variety of industrial sectors.

ABSTRACT Liposomal nanocarriers are clinically established platforms for targeted drug delivery due to their biocompatibility and ability to encapsulate both hydrophilic and hydrophobic agents. However, conventional single‐drug liposomes are limited by suboptimal efficacy, systemic toxicity, and multidrug resistance. Dual‐drug‐loaded liposomes (DDLs) address these limitations by enabling co‐delivery of synergistic agents within a single nanocarrier. This review provides an integrated analysis of DDL systems, focusing on formulation design, drug loading strategies, and key physicochemical parameters governing encapsulation efficiency and controlled release. Mechanistic insights into therapeutic enhancement are highlighted, including modulation of efflux transporters, reversal of epithelial–mesenchymal transition, and synchronized intracellular delivery. The impact of ligand‐mediated functionalization on tumor targeting and cellular uptake is also critically evaluated. Unlike existing reviews, this work provides a unified framework integrating formulation design, mechanistic insights into drug synergy, and translational challenges specific to DDLs, addressing a critical gap in the existing literature. Preclinical and clinical evidence, including approved formulations such as Vyxeos, is discussed. Remaining barriers include scale‐up, reproducibility, immune interactions, and regulatory complexity. Future directions emphasize personalized and stimulus‐responsive nanomedicine for improved cancer therapy.

Endosulfan is a broad-spectrum organochlorine pesticide widely used in many developing countries despite its high toxicity potential. Endosulfan, listed as potent endocrine-disrupting chemical and xenoestrogen, gains importance for its potential to cause reproductive and developmental dysfunction. In females, endosulfan disrupts ovarian and uterine development, leading to infertility, miscarriage, and developmental toxicity. It acts by mimicking estrogen and interferes with estrogen and androgen pathways, impacting hormone regulation and gene expression, including estrogen receptor α (ERα) and progesterone receptors. Endosulfan triggers oxidative stress in ovaries, reduces follicle count, and impairs uterine differentiation, affecting embryo implantation. Additionally, it alters gene expression and causes epigenetic modifications, contributing to reproductive dysfunctions. In males, endosulfan affects spermatogenesis by causing oxidative stress, mitochondrial dysfunction, and lipid peroxidation. It reduces sperm quality, motility, and quantity, with effects on testicular tissues, sperm chromatin condensation, and enzymatic activity. Oxidative damage, increased reactive oxygen species (ROS), and disrupted energy metabolism are central to its toxicity. Epidemiological studies also link pesticide exposure to reduced sperm counts, higher DNA fragmentation, and infertility. Moreover, endosulfan can cross the placental barrier, leading to fetal resorption, malformations, and maternal toxicity. This review provides a comprehensive overview of the reproductive toxicity of endosulfan in males and females. We also highlight the various possible mechanisms of reproductive toxicity of endosulfan and its potential to impart deleterious effects over HPG axis, gonads, and uterine differentiation and development and implantation.

Aprepitant (APT), an antiemetic drug used for chemotherapy-induced nausea and vomiting (CINV), exhibits poor compressibility, solubility, and micromeritic properties. Crystal habit modification was studied using solvent evaporation, conventional antisolvent crystallization (APT_AS), cooling crystallization (APT_CC), and the advanced sonocrystallization technique (APT_SN). Morphological analysis of the sonocrystallized crystals revealed small, platy crystals exhibiting an aspect ratio of 1.35 ± 0.04 and a span value of 1.06. The APT_SN showed improved micromeritics as compared to APT_AS (1.59 ± 0.03) and APT_CC (1.48 ± 0.04) (antisolvent-crystallized APT and cooling crystallized APT, respectively). All modified crystals exhibited a plate-shaped crystal habit with no agglomeration. The angle of repose, Carr’s index, and Hausner’s ratio exhibit that the APT_SN showed improvement in powder properties. Solid-state characterization using differential scanning calorimetry (DSC), Powder X-ray Diffraction Spectroscopy (PXRD), and Thermogravimetric Analysis (TGA) proved no change in polymorph. Contact angle-driven wettability was as follows: APT > APT_AS > APT_SN > APT_CC, and the results were corroborated by X-ray photon spectroscopy (XPS) and intrinsic dissolution profiles. The XPS studies revealed a decrease in the surface polar component of APT_SN, resulting in reduced wettability. APT_SN showed the highest tensile strength at 20 kg/cm2 among all other crystals. All the modified crystals exhibited a reduced IDR profile, resulting from a reduction in the polar component at the surface.

Carbon quantum dots (CQDs) are widely explored for bioimaging, drug delivery, and theranostic applications due to their tunable fluorescence, biocompatibility, and adaptable surface chemistry. Nevertheless, precise hydrophobic-hydrophilic tuning from a single precursor remains underdeveloped, as most approaches depend on postsynthetic modification or multiple carbon sources, which can introduce additional processing steps and variability in surface composition. A single-precursor strategy may help simplify the synthesis and provide more consistent control over surface functionalities, offering a more direct route to polarity-tuned CQDs. Herein, we report a single-precursor-directed strategy to generate CQDs with distinct surface polarities, enabling controlled spatial organization within liposomal nanostructures. Curcumin was utilized as the carbon source in a solvothermal process conducted in the absence and presence of 3-aminopropyltrimethoxysilane, producing hydrophobic (Hb-CQD) and hydrophilic (Hp-CQD) carbon dots, respectively. The engineered polarity contrast dictated their interfacial behavior: Hb-CQDs preferentially embedded within the hydrophobic lipid bilayer (L-Hb-CQD), Hp-CQDs localized in the aqueous core of liposomes (L-Hp-CQD), and liposome-in-liposome (L-Hb-CQD-in-L-Hb-CQD) system. Encapsulation conditions were optimized to ensure homogeneous dispersion, improved colloidal stability, and enhanced intrinsic fluorescence of both CQD systems. Encapsulation efficiency, structural integrity, and spatial localization were systematically verified using fluorescence spectroscopy, TEM, and confocal laser scanning microscopy. The polarity control from a unified precursor platform demonstrates a rational route for directing nanoscale positioning of carbon dots within biomimetic architectures. The approach provides a versatile framework for designing multifunctional nanohybrids with potential applications in advanced bioimaging, controlled drug delivery, integrated theranostics, and mechanistic studies of nanoparticle-membrane interactions.

The atomic-level crystal structure is crucial in determining the physicochemical characteristics of pharmaceutical solids; therefore, accurate crystal structure determination is essential for pharmaceutical development. Many active pharmaceutical ingredients (APIs) and multi-component systems exist only as micro or nanocrystalline material, which limits the applicability of conventional single-crystal X-ray diffraction. Co-crystals, which offer a multitude of pharmaceutical and biopharmaceutical upper edge are a major part of these multi-component systems and face the issue that they are obtained in micron-sized crystals. Recent progress in three-dimensional electron diffraction (3DED) has addressed this challenge by enabling structure determination from tiny crystals. This review delves into the relationship between atomic-level structure and physicochemical properties of pharmaceuticals, highlighting how MicroED (Microcrystal Electron Diffraction) enables atomic-resolution structure determination from sub-micron crystals. Primary applications include polymorph identification and characterization, structural analysis of pharmaceutical co-crystals, and the detection of trace or hidden crystallinity in materials previously classified as amorphous. In addition, this review features representative case studies demonstrating the successful application of MicroED to pharmaceutical solids and emphasizes its integration with complementary analytical methods such as Raman spectroscopy, Solid-state NMR, and Powder X-ray diffraction (PXRD). The authors have discussed in detail how MicroED is an effective approach for solid-state characterisation, supporting early-stage decision-making, quality control, and systematic solid form development in pharmaceuticals. Authors have emphasized and provide detailed explanation how MicroED is going to be a game changer once it becomes easily accessible to pharmaceutical scientists.

Melatonin, traditionally recognized for its role in regulating circadian rhythms and sleep, has emerged as a multifunctional molecule with significant implications in dermatology. Melatonin is described here as a pleiotropic, context-dependent modulator with antioxidant-related and immunomodulatory actions that are supported by both direct chemical scavenging in cell-free systems and indirect, enzyme-mediated effects in cells and tissues; its antitumor activity in dermatology is primarily preclinical and remains to be confirmed in large clinical trials. Melatonin protects skin cells from oxidative stress, UV radiation, and environmental damage by directly scavenging free radicals and activating endogenous defense systems. It also modulates immune responses, making it relevant in inflammatory dermatoses such as atopic dermatitis, while promoting tissue repair in wound healing and reducing signs of skin aging. Particular attention is given to topical formulations, including gels, creams, and patches, which enable localized delivery, improved skin penetration, and reduced systemic side effects. The review also discusses ongoing clinical trials, delivery technologies, and the potential for combinatorial therapies with established dermatological agents.

A standardized polyphenol-enriched fraction (IPHRFPPEF) was formulated into a phospholipid complex (IPHRFPPEF-PC) to enhance oral bioavailability and evaluate stability, toxicity, and in vivo anti-inflammatory activity in Sprague Dawley rats. IPHRFPPEF was prepared from crude extract using XAD-HP7/Diaion-HP20 resin column chromatography and analyzed via HPLC and NMR. Total phenolic and flavonoid contents were quantified, with IPHRFPPEF showing higher values than the crude fraction. The phospholipid complex was prepared via solvent evaporation and assessed for bioavailability, stability, and toxicity. Key results demonstrated a 1.99-fold, 2.03-fold, and 1.66-fold increase in plasma concentrations of isorhamnetin, kaempferol and quercetin respectively. Acute oral toxicity testing showed an LD50 of 5000 mg/kg (GHS Category 5), and repeated-dose studies confirmed safety. IPHRFPPEF-PC exhibited enhanced pharmacokinetics and potent in vivo anti-inflammatory effects. In conclusion, the development of IPHRFPPEF-PC from a standardized polyphenol-enriched fraction offers a safe and effective therapeutic approach, with significant potential for future applications in treating inflammatory conditions.

Breast cancer continues to be a predominant cause of death among women globally, necessitating the development of more effective and targeted treatment strategies. While current therapies have shown efficacy, they are often associated with notable adverse effects and inadequate tumor targeting. This review explores the potential of stimuli-responsive zeolitic imidazole framework-8 (ZIF-8) metal-organic frameworks (MOFs) in the treatment of breast cancer. Composed of zinc ions and imidazolate linkers, ZIF-8’s structure offers pH-sensitive degradation, making it ideal for precise medication delivery in the acidic tumor microenvironment. We investigate various synthesis methods and emphasize the advantages of ZIF-8 in enhancing drug bioavailability and precision targeting. The stimuli-responsive properties of ZIF-8 MOFs—such as responsiveness to pH, light, temperature, ultrasound, redox conditions, and enzymes—enable controlled and site-specific drug release. Furthermore, we examine the integration of ZIF-8 MOFs with existing breast cancer therapies and their applications in diagnostics and imaging. Consideration is also given to the biocompatibility of ZIF-8 to ensure safe and effective clinical use. This review article offers a comprehensive analysis of the function of stimuli-responsive ZIF-8 MOFs in transforming breast cancer therapy and facilitating novel treatment approaches.

Crystal habit modification potentially improves the pharmaceutical and biopharmaceutical properties related to active pharmaceutical ingredients (APIs) and is an important aspect of crystal engineering.