Pharmaceutical Research[JOURNAL]
Sun
200 papers
How Breathing Interruptions Influence pMDI Aerosol Delivery: A CFD Study in a Realistic Airway.
Jahed M, Kozinski J, Pakzad L
Pharm Res · 2026 Feb · PMID 41372693 · Publisher ↗
OBJECTIVE: The effectiveness of pressurized metered-dose inhalers (pMDIs) relies on correct inhalation technique. While prior studies investigated idealized breathing, the impact of real-life irregularities remains less...
OBJECTIVE: The effectiveness of pressurized metered-dose inhalers (pMDIs) relies on correct inhalation technique. While prior studies investigated idealized breathing, the impact of real-life irregularities remains less understood. This study explores how real-life irregularities-pausing, coughing, and premature exhalation-alter aerosol transport and deposition in the airways. METHODS: Large-eddy simulations combined with a discrete phase model were performed on a realistic male airway geometry extending from the oral cavity to the fourth bronchial generation. Computational predictions were validated against in vitro experiments conducted under constant inhalation. RESULTS: Breathing irregularities substantially modified airflow dynamics and shifted deposition toward the upper airways. Coughing generated the strongest vortical structures and turbulence, followed by premature exhalation. Deposition in the left lung decreased from 19.9% during standard COPD inhalation to 2.1% during exhalation and 0.9% during coughing, while mouth-throat deposition increased to 35.2% during coughing compared to 14.5% under the COPD baseline condition. Exhalation caused higher overall particle loss (27.9%) than coughing (24.1%), but coughing produced more pronounced inertial impaction in the upper airways. Fine particles (< 2 µm) were largely exhaled (approximately 80%), whereas particles in the 2-5 µm range-considered optimal for deep lung delivery-were redirected and lost under disturbed flow conditions. CONCLUSIONS: Irregular breathing patterns markedly decrease deep lung deposition and increase upper airway losses. Repeated puffs without adequate intervals may exacerbate this problem, leading to excessive upper-airway deposition and increasing the likelihood of side effects. These findings provide guidance for physicians to tailor puff number and timing, improving therapeutic efficacy while minimizing risks to patient safety.
Rational Design of a Bioconjugated Antitumor Peptide with Tumor-Selective Targeting and Microenvironment-Responsive Activation.
Feng C, Deng W, Cai M … +4 more , Hu Y, Liang W, Dong H, Rui M
Pharm Res · 2026 Jan · PMID 41372692 · Publisher ↗
OBJECTIVE: Bioactive peptides derived from natural or synthetic sources have shown significant potential for cancer therapy; however, their clinical application is often limited by poor tumor selectivity and systemic tox...
OBJECTIVE: Bioactive peptides derived from natural or synthetic sources have shown significant potential for cancer therapy; however, their clinical application is often limited by poor tumor selectivity and systemic toxicity. In this work, we aim to develop a multifunctional antitumor peptide with enhanced tumor- targeting capability and therapeutic efficacy. METHODS: A cationic antimicrobial peptide (AMP, (KKWW) K-NH) was chemically modified via cysteine-mediated conjugation with 4-vinylphenylboronic acid, yielding the phenylboronic acid-conjugated AMP (PBA-AMP). Molecular dynamics (MD) simulations were performed to evaluate peptide-membrane interactions. Cellular uptake, cytotoxicity, and in vivo tumor-targeting and antitumor efficacy were assessed using MCF-7 cells and 4T1 tumor-bearing mice. RESULTS: MD simulations demonstrated that PBA-AMP exhibited rapid and stable binding to tumor cell membranes, maintaining consistent membrane interactions over a 50 ns simulation. Cellular studies revealed enhanced cellular uptake and increased cytotoxicity of PBA-AMP against MCF-7 breast cancer cell line (IC = 38.46 μM) compared to naive AMP (IC = 110 μM). In vivo imaging confirmed selective and prolonged tumor accumulation of PBA-AMP. Treatment with PBA-AMP significantly suppressed tumor growth in 4T1 tumor-bearing mice without observable systemic toxicity. CONCLUSIONS: This study presents a rational design strategy for engineering tumor-selective, microenvironment-responsive therapeutic peptides. PBA-AMP represents a promising candidate for targeted cancer therapy, offering improved efficacy and reduced off-target effects.
Development and optimisation of Polyelectrolyte Complex Nanoparticles Loaded with Sorafenib by Central Composite Design (CCD): In Vitro and In Vivo Studies for the Treatment of Triple Negative Breast Cancer.
Kale SA, Deokar SS, Shaikh KS
Pharm Res · 2025 Dec · PMID 41372691 · Publisher ↗
INTRODUCTION: Sorafenib (SOR) is a low-dose multikinase inhibitor that suppresses angiogenesis by blocking vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors. The aim of the pre...
INTRODUCTION: Sorafenib (SOR) is a low-dose multikinase inhibitor that suppresses angiogenesis by blocking vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors. The aim of the present study was to develop Sorafenib-loaded chitosan (CS) and hyaluronic acid (HA) polyelectrolyte complex nanoparticles (SCH-NP) for triple negative breast cancer (TNBC). METHODS: For TNBC therapy, SCH-NP were formulated and optimized using Central Composite Design (CCD). The prepared SCH-NP were characterized by particle size, zeta potential, Polydispersity index, Fourier Transform Infrared Spectroscopy (FTIR), entrapment efficiency, invitro drug release study, in-vitro and in vivo studies. RESULTS: SCH-NP were formulated and optimized using CCD. The developed SCH-NP showed particle size of 125 nm, zeta potential of -13.7 mV, PDI value 0.21 and entrapment efficiency of 82.07%. FTIR study confirmed no interaction between drug and polysaccharide. The cumulative release percentage of SOR from SCH-NP was 81.73%. SOR's IC50 value was much larger than, SCH-NP's in both MDA-MB 231 & 4T1 cell lines. After treatment for 18 days, the tumor volumes in mice increased to 447.4 mm (Phosphate buffer solution), 263.6 mm (pure SOR), treatment with SCH-NP results in a noteworthy decrease in the tumor volumes in mice by 66.1% (151.3 mm). CONCLUSIONS: The present study suggests that SCH-NP might be effective for the tumor-targeted delivery of Sorafenib and it might be a suitable nanocarrier for enhancing SOR cytotoxicity in vitro and may be useful for the tumor-targeted delivery of SOR.
Particle-Size-Determined Crystallization and Dissolution Behavior of Amorphous Griseofulvin.
Košťálová D, Svoboda R, Kozlová K … +2 more , Nevyhoštěná M, Komersová A
Pharm Res · 2026 Jan · PMID 41372690 · Full text
PURPOSE: Amorphous active pharmaceutical ingredients (APIs) are generally considered to have significantly higher bioavailability, compared to their crystalline counterpart, due to the enhanced solubility of the disorder...
PURPOSE: Amorphous active pharmaceutical ingredients (APIs) are generally considered to have significantly higher bioavailability, compared to their crystalline counterpart, due to the enhanced solubility of the disordered phase. However, an akin functionality can be also adopted by the particle size of the powdered API. In this case study, a detailed investigation of the particle-size-influenced properties of amorphous griseofulvin powders will be introduced. METHODS: The crystallization of amorphous griseofulvin powders in the range 20 - 1000 μm (+ 2 - 10 μm only for crystalline form) was studied calorimetrically, spectroscopically, and microscopically. Dissolution profiles of pharmaceutical tablets with incorporated either amorphous or crystalline griseofulvin were obtained under conditions simulating the path through the gastrointestinal tract. RESULTS: Standard crystal growth regime was accompanied by the rapid diffusionless growth mode, which was detected at low heating rates for the finest griseofulvin powders. The dissolution profiles of the pharmaceutical tablets with incorporated individual griseofulvin powder fractions were described in terms of the Korsmeyer-Peppas model (indicating the release by super case II transport). CONCLUSION: Particle size was found to play dominant role in the dissolution kinetics, whereas the difference in the dissolution rates of the crystalline and amorphous particles was rather negligible. This is a beneficial finding, considering the very low stability of finely powdered amorphous griseofulvin, but at the same time, it negates the primary purpose of amorphization. Main benefit is thus that of the coarse amorphous griseofulvin powder, which can be utilized to fine-tune the dissolution profile due to its delayed dissolution.
Expression and Functional Evaluation of ABC and SLC Transporters in Human Choroid Plexus Papilloma (HIBCPP) Cells: A Human Blood-Cerebrospinal Fluid Barrier Model.
Kurosawa T, Ohtsuki S, Ishikawa H … +4 more , Schroten H, Schwerk C, Kubo Y, Deguchi Y
Pharm Res · 2026 Jan · PMID 41372689 · Full text
PURPOSE: Human choroid plexus papilloma (HIBCPP) cells derived from choroid plexus papilloma in the lateral ventricle are considered suitable model cells for the blood-cerebrospinal fluid barrier (BCSFB). Therefore, in t...
PURPOSE: Human choroid plexus papilloma (HIBCPP) cells derived from choroid plexus papilloma in the lateral ventricle are considered suitable model cells for the blood-cerebrospinal fluid barrier (BCSFB). Therefore, in this study, the transporters expressed in HIBCPP cells were identified, and the functions of representative transporters were evaluated. METHODS: Transporter protein and mRNA expression were analyzed in HIBCPP cells using quantitative proteomics and quantitative reverse transcription-PCR. Transporter functions were evaluated by cellular uptake and transcellular transport studies using typical substrates. RESULTS: The following solute carrier (SLC) and ATP-binding cassette (ABC) transporters involved in drug and nutrient transport were expressed in HIBCPP cells: glucose transporter 1 (GLUT1), monocarboxylate transporter 1 (MCT1), L-type amino acid transporter 1 (LAT1), cationic amino acid transporter 1 (CAT1), glutamate transporter (GLAST), SLC35F2, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). Furthermore, the mRNA of organic anion/cation transporters, such as organic anion transporting polypeptide 1B3 (OATP1B3) and plasma membrane monoamine transporter (PMAT), were detected. Additionally, uptake of representative substrates of the SLC transporters LAT1, CAT1, GLAST, GLUT1, MCT1, and SLC35F2 in HIBCPP cells occurred in a time- and temperature-dependent manner and decreased in the presence of specific inhibitors. Furthermore, the representative substrates of these transporters were transported in a symmetric or asymmetric manner through HIBCPP cells between the apical (cerebrospinal fluid [CSF]) and basolateral (blood) sides. CONCLUSION: Various nutrient and drug transporters are functionally expressed in HIBCPP cells. Therefore, HIBCPP cells could serve as a useful human BCSFB model to evaluate nutrient and drug transport between the CSF and blood.
Investigation of Phytol as an Inhibitor of the Efflux Pump (QacA/B) in Staphylococcus aureus: in silico and in vitro Studies.
Almeida-Bezerra JW, Dos Santos CAL, Menezes SA … +15 more , de Morais Oliveira-Tintino CD, da Cruz RP, Costa AR, Rocha JE, Alves DS, de Sousa SG, de Sousa Rodrigues EY, Alencar GG, Filho JMB, da Silva VB, Tintino SR, de Menezes IRA, da Costa Silva JT, Morais-Braga MFB, Coutinho HDM
Pharm Res · 2026 Jan · PMID 41372688 · Publisher ↗
OBJECTIVE: Staphylococcus aureus is a microorganism that can behave as a commensal or as a life-threatening pathogen. Its remarkable capacity to acquire resistance to antimicrobial agents, particularly through mechanisms...
OBJECTIVE: Staphylococcus aureus is a microorganism that can behave as a commensal or as a life-threatening pathogen. Its remarkable capacity to acquire resistance to antimicrobial agents, particularly through mechanisms such as efflux pumps, places it among the major contributors to global morbidity and mortality. In this study, the acyclic diterpene phytol was investigated for its potential as an efflux pump inhibitor (EPI). Molecular docking was performed to evaluate its interaction with the QacA/B efflux pump, followed by in silico prediction of ADMET properties. In addition, the inhibitory effect of phytol on efflux activity was assessed in vitro against S. aureus. METHODS: To this end, the Minimum Inhibitory Concentration (MIC) was determined through serial microdilution in broth. The evaluation of efflux pump inhibition was assessed by measuring the reduction in MIC of ampicillin and ethidium bromide (EtBr) when combined with phytol at sub-inhibitory concentrations (MIC/8). RESULTS: Docking results showed that phytol has an average binding affinity of -4.7 kcal/mol with QacA, interacting with several amino acids at the binding site, additionally, the ADMET evaluation reveals Phytol as a promising compound for demonstrating low toxicological capacity. CONCLUSIONS: However, despite the in silico interactions, the diterpene did not demonstrate direct antibacterial activity nor did it reduce the MIC of ampicillin or ethidium bromide, indicating that it does not function as an EPI.
From Clinical Trials to Commercialization: Perspectives in Human Vaccine.
Mehrotra N, Manchikanti P
Pharm Res · 2026 Jan · PMID 41372687 · Publisher ↗
Although India ranks among the largest producers and exporters of human vaccines, the delay in launch of newer therapeutics is larger than the average in G20 nations. This study aims to assess the stakeholders' perspecti...
Although India ranks among the largest producers and exporters of human vaccines, the delay in launch of newer therapeutics is larger than the average in G20 nations. This study aims to assess the stakeholders' perspective on the coherence, clarity, and operational impact of the New Drugs and Clinical Trial (NDCT) Rules 2019. The analysis revealed a nuanced appraisal of the NDCT Rules wherein three major clusters of challenges faced by pharmaceutical companies are regulatory, operational, and systemic. The regulatory barriers encompass prolonged approval timelines, ambiguous legal mechanisms, fragmented oversight across agencies. Operational factors include uneven distribution of trial sites, inadequate site capacity, ethics committee delays. Systemic challenges centred on non-uniform trial protocols, inconsistent documentation practices and absence of harmonized operational guidelines.
Trimorphism in riluzole salicylate: screening, crystal structures and solution thermodynamics.
Voronin AP, Ramazanova AG, Vologzhanina AV … +1 more , Perlovich GL
Pharm Res · 2026 Jan · PMID 41366189 · Publisher ↗
PURPOSE: This study investigated the phenomenon of polymorphism in the pharmaceutical salt riluzole salicylate with the aim to modify the aqueous solubility and dissolution rate of riluzole. METHODS: Preparation routes a...
PURPOSE: This study investigated the phenomenon of polymorphism in the pharmaceutical salt riluzole salicylate with the aim to modify the aqueous solubility and dissolution rate of riluzole. METHODS: Preparation routes and transformation pathways were investigated using mechanoactivation, sonication, sublimation and melt crystallization. The thermal-induced phase transformations were interpreted by thermal microscopy and ex situ PXRD analysis. The crystal structure of Form 3 was solved from powder diffraction data. The differences in non-covalent interactions in crystals of Form 1 and Form 3 and their role in structure stabilization were studied by QTAIMC analysis, fingerprint plots, energy frameworks and lattice energy calculations. Cocrystallization thermodynamic functions and relationships between three polymorphs were established based on DSC, solubility and lattice energy data. RESULTS: Two novel polymorphs of riluzole salicylate with higher melting points were discovered and characterized in addition to reported Form 1. The stable Form 3 can be obtained easily by milling or from the slurry, while the metastable Form 2 forms only by melt crystallization or resublimation. Form 3 has stronger hydrogen bonding and more balanced non-covalent interactions than Form 1, making it thermodynamically favored at room temperature, while Form 1 is more stable near absolute zero. CONCLUSION: Polymorphism significantly affects the pharmaceutical properties of riluzole salicylate. Selective preparation of polymorphs enables tuning of solubility and dissolution, linking crystal structure and thermodynamics to drug delivery optimization. Slower release kinetics of Form 1 compared to Form 3 and parent RLZ indicates its potential use as a prolonged form.
Transdermal Drug Delivery Systems: A Comprehensive Review of Mechanisms, Technologies, and Clinical Applications.
Xu F, Qiu Z, Zhang M … +6 more , Ren Y, Kong L, Liu Y, Zhang T, Wang C, Wang P
Pharm Res · 2025 Dec · PMID 41350970 · Publisher ↗
BACKGROUND: Transdermal Drug Delivery Systems (TDDS) offer a non-invasive route for sustained systemic or localized drug delivery. By bypassing hepatic first-pass metabolism and improving bioavailability, TDDS enhances p...
BACKGROUND: Transdermal Drug Delivery Systems (TDDS) offer a non-invasive route for sustained systemic or localized drug delivery. By bypassing hepatic first-pass metabolism and improving bioavailability, TDDS enhances patient compliance, especially in the management of chronic diseases. Drug permeation across the skin is mediated through pathways involving the complex skin barrier, predominantly the stratum corneum, with efficacy influenced by both drug properties and skin physiology. METHODS: This review systematically integrates the fundamental mechanisms underlying TDDS, highlights cutting-edge technological advancements developed to overcome the skin barrier, and discusses their expanding clinical applications. The advanced technologies covered include permeation enhancers, vesicular systems (liposomes, transfersomes, ethosomes), microemulsions, microneedles (MNs), responsive systems (pH-, temperature-, enzyme-sensitive), and 3D printing. RESULTS: These innovative technologies effectively enhance drug flux, enable targeted delivery, and achieve spatiotemporal control of drug release. Clinically, FDA-approved TDDS formulations have been successfully applied to manage various conditions, including chronic pain (fentanyl, buprenorphine), neurological disorders (rotigotine, rivastigmine), cardiovascular diseases (nitroglycerin, clonidine), hormone replacement, and substance dependence (nicotine). Despite significant clinical value, TDDS still faces challenges such as limitations in delivering macromolecules, potential skin irritation, and inter-individual variability. CONCLUSION: Future directions in TDDS research focus on integrating nanotechnology, AI-driven optimization, wearable sensors, and closed-loop smart systems. These integrations aim to achieve greater precision, personalization, and efficiency in transdermal drug delivery, providing valuable insights for future research and translational development.
QbD Optimized Nanoemulsion Based Topical Formulation of Jatyadi Taila: Unveiling its In Vitro and In Vivo Efficacy for Enhanced Wound Healing.
Chavan SV, Guha S, Raza K … +4 more , Pandit RK, Pandit K, Pandey MM, Chitkara D
Pharm Res · 2025 Dec · PMID 41350969 · Publisher ↗
BACKGROUND: Jatyadi Taila (JT) is an Ayurvedic herbal formulation traditionally used for wound healing. However, its oily nature restricts clinical use due to greasy texture, slower absorption, occlusiveness, and applica...
BACKGROUND: Jatyadi Taila (JT) is an Ayurvedic herbal formulation traditionally used for wound healing. However, its oily nature restricts clinical use due to greasy texture, slower absorption, occlusiveness, and application difficulties, resulting in poor patient compliance. OBJECTIVES: To develop and optimize a JT containing nanoemulsion (JT-NE) and incorporate it into a Carbopol-based hydrogel for enhanced wound healing efficacy. METHODS: JT-NE was developed using a Quality by Design (QbD) approach and incorporated into a Carbopol-based hydrogel. The formulations were characterized for physicochemical properties, rheology, and morphology. In vitro fibroblast proliferation and migration assays, along with in vivo wound healing studies in full-thickness wound-bearing Wistar rats, were performed to evaluate therapeutic efficacy. RESULTS: The optimized JT-NE formulations exhibited a globule size range of 220-300 nm, polydispersity index (0.245-0.380), and zeta potential values of -25.94 ± 1.01 mV, 18.14 ± 1.20 mV, and -26.10 ± 1.25 mV. Hydrogels containing JT-NE demonstrated thixotropic behavior with an average viscosity of 88748 mPa, pH 4.5-5.5, a porous mesh-like morphology with entrapped JT-NE, and ~70% water loss within 4 h. In vitro, JT-NE significantly promoted fibroblast proliferation and migration. In vivo, the formulation enhanced wound closure, increased collagen biosynthesis, downregulated TNF-α, and upregulated KI-67 expression compared to untreated and JT treated groups. CONCLUSION: The JT-NE hydrogel significantly improved the therapeutic efficacy of JT, offering a novel, patient-compliant delivery system for effective wound management.
Photosensitizer-Antibody Conjugates (PhotoBodies): Emerging Frontiers in the Field of Theranostics.
Kulkarni SS, Khandave PY, Tiwatane AK … +3 more , Rawat K, Bhaumik J, Pande AH
Pharm Res · 2026 Jan · PMID 41350968 · Publisher ↗
BACKGROUND: The beginning of precision medicine has come to rise in a new era of targeted therapies. Among these innovations, light-activatable antibody photo drug conjugates/photoimmunoconjugates termed as "PhotoBodies"...
BACKGROUND: The beginning of precision medicine has come to rise in a new era of targeted therapies. Among these innovations, light-activatable antibody photo drug conjugates/photoimmunoconjugates termed as "PhotoBodies" have emerged as next-generation theranostic agents. By remaining inert until irradiated with a specific wavelength, PhotoBodies offer controlled diagnosis or treatment of diseased cells, tissues, or organs. OBJECTIVE: This review aims to summarize the evolution of new generation of photosensitizers, linkers, and antibody formats employed in PhotoBodies, to assess current preclinical and clinical developments, to identify unaddressed challenges, and propose a roadmap for future PhotoBodies. METHODS: We conducted a comprehensive literature survey focusing on studies reporting the designing and theranostic applications of PhotoBodies in both preclinical models and clinical trials. RESULTS: More than 15 PhotoBodies are currently in clinical trials for targeted diagnosis and two for therapeutic application in cancers. PhotoBodies have also demonstrated their flexibility to combat the silent pandemic of the world i.e., non-oncological. Advances in photosensitizer chemistry have improved photostability, singlet-oxygen quantum yield, and tissue penetration. From conventional antibodies (full length antibodies/mAb) to non-conventional antibodies (antibody fragments including Fab, F(ab')₂, scFv, diabodies, minibodies, and single-domain antibodies), all the formats have been explored to balance the pharmacokinetics of PhotoBodies with tissue accessibility. PolyBodies based antibody partners in PhotoBodies have begun to enhance the clinical utility of PhotoBodies by improving their targeting efficacy. However, promising future includes key hurdles such as optimizing light delivery in deep tissues, managing immunogenicity, standardizing conjugation protocols, and navigating regulatory pathways. CONCLUSION: PhotoBodies represent a promising frontier in precision theranostics by combining the specificity of antibody targeting with the controllability of photochemistry. Continued refinement of photosensitizer, linkers and antibody engineering will accelerate the clinical translation of PhotoBodies and realize their full potential in next-generation precision medicine. PolyBodies (containing polyvalent and polyspecific) based antibody carriers possess an upper hand in changing the current landscape of PhotoBodies and redefine their future.
Biotechnology in Brazil: Current State, Gaps, and Strategic Recommendations.
Martins FS, Bottos G, Silva Hecktheuer A … +1 more , Luiz Borges L
Pharm Res · 2026 Jan · PMID 41350967 · Publisher ↗
Biotechnology is becoming a key driver of innovation in health, agriculture, industry, and sustainability worldwide. Brazil has made significant progress in this field, thanks to its strong research institutions, diverse...
Biotechnology is becoming a key driver of innovation in health, agriculture, industry, and sustainability worldwide. Brazil has made significant progress in this field, thanks to its strong research institutions, diverse ecosystems, and active pharmaceutical and agribusiness sectors. However, despite these strengths, the country still faces critical barriers that limit its global competitiveness in biotechnology. These include a lack of coordination between academia and industry, limited early-stage investment, underdeveloped infrastructure, regulatory delays, and low levels of internationalization. This article provides a comprehensive overview of the biotechnology landscape in Brazil. It analyzes the global context, highlights the country's current position, and identifies gaps and opportunities across the biopharmaceutical value chain. Drawing from international benchmarks and national data, the paper proposes five strategic directions to strengthen Brazil's biotechnology ecosystem: (1) fostering translational science and innovation; (2) expanding access to capital and reducing investment risk; (3) improving infrastructure through shared platforms; (4) modernizing regulatory frameworks; and (5) positioning Brazil in global markets through its unique strengths, such as biodiversity, public health expertise, and agricultural leadership. The article concludes that Brazil has the scientific foundation and market potential to become a global player in biotechnology. However, realizing this potential will require coordinated efforts from government, industry, and academia. With the right policies and investments, Brazil can turn scientific advances into innovative solutions that benefit both its population and the global bioeconomy.
Emerging Role of Nanostructured Lipid Carriers in Overcoming Cancer Treatment Challenges.
Deore RT
Pharm Res · 2025 Dec · PMID 41345327 · Publisher ↗
Cancer continues to remain a global health challenge, and conventional chemotherapy has its own limitations such as poor solubility, systemic toxicity, nonspecific biodistribution, and multidrug resistance (MDR). Nanostr...
Cancer continues to remain a global health challenge, and conventional chemotherapy has its own limitations such as poor solubility, systemic toxicity, nonspecific biodistribution, and multidrug resistance (MDR). Nanostructured Lipid Carriers (NLCs) have proved as one of the effective drug delivery systems which can overcome all challenges of conventional technologies by enhancing therapeutic efficacy with reduced side effects. Therefore, this comprehensive review describes, in detail the structure, composition, formulation characteristics of NLCs, and manufacturing techniques. NLCs have shown significant advantages including enhanced drug solubility, controlled release characteristics, and encapsulation of hydrophilic as well as lipophilic drugs. Passive and active targeting enables NLCs to maximize the accumulation of drugs at targeted tumor sites through the enhanced permeation retention (EPR) effect. In addition, MDR targeting and long-circulating NLCs can enhance effectiveness against the resistance mechanisms of cancer cells. Cancer theranostics integrated with NLCs provide real-time diagnosis and treatment opportunities. Despite all these potential advantages, NLCs are still facing a few challenges of large-scale manufacturing, toxicity issues, and regulatory approvals. Yet, recent progress in personalized medicine and lipid-based nanotechnology reflects the potential of NLCs as a versatile and efficient delivery system for anticancer drugs. This review tries to clarify the evolving aspect of NLCs as well as the challenges faced in cancer treatment and strategies to overcome them by focusing on their ability to reshape chemotherapy and improve patient compliance.
Machine Learning Prediction of Protein Adsorption on Drug-delivering Nanoparticles: A Literature Survey and Need for Future Development.
Basu K, Chelagamsetty VS, Ruiz-Avila VA … +1 more , Li T
Pharm Res · 2026 Jan · PMID 41298984 · Full text
Nanoparticles (NPs), due to their small size and large surface area, have advanced their use as drug carriers for delivering various therapeutic molecules. When entering biological environments, nanoparticles typically a...
Nanoparticles (NPs), due to their small size and large surface area, have advanced their use as drug carriers for delivering various therapeutic molecules. When entering biological environments, nanoparticles typically adsorb proteins, forming a surface layer known as a protein corona that significantly affects the biological and therapeutic functions of a delivery system. Understanding and predicting protein adsorption is essential for optimizing nanoparticle design in drug delivery, diagnostics, and therapy. Machine learning and deep learning (ML/DL) offer promising methods for designing nanoparticles with specific properties, particularly given recent advancements in computation and nanoparticle analysis. This review explores ML/DL studies of nanoparticle-protein interactions and emphasizes the popularity of Random Forest (RF) and Deep Learning (DL) models in predicting protein corona compositions. RF models are highly valued for managing high-dimensional data and offering interpretability, which helps identify key NP features influencing protein adsorption. Conversely, DL excels at modeling non-linear relationships and detecting subtle interaction patterns. While most current research focuses on protein coronas, future models may also include other biocorona components. This is particularly relevant for soft materials, such as lipid nanoparticles (LNPs), which are now approved for delivering mRNA and peptide-based vaccines. Our findings underscore the need for advanced modeling techniques and high-quality, diverse experimental data to drive innovations in nanomedicine. Combining RF and DL approaches leverages their complementary strengths to overcome the challenge of limited experimental data and further improve NP designs for biomedical use.
Comparative Formulation and Physicochemical Evaluation of Orodispersible Films Fabricated via Pneumatic and Syringe-Based 3D Printing.
Poudel I, Mita N, Scherer J … +5 more , Annaji M, Kang X, Fasina O, Tiwari AK, Babu RJ
Pharm Res · 2025 Dec · PMID 41298983 · Full text
OBJECTIVE: Orodispersible films (ODF) blend the dose accuracy of solid dosage forms and the ease of administration of liquid dosage forms, hence offer many advantages. This study investigated the feasibility of two extru...
OBJECTIVE: Orodispersible films (ODF) blend the dose accuracy of solid dosage forms and the ease of administration of liquid dosage forms, hence offer many advantages. This study investigated the feasibility of two extrusion-based 3D printing techniques (pneumatic and syringe) to fabricate ODFs in a benchtop setting. METHODS: We fabricated fast-dissolving ODFs using pneumatic and syringe print heads and compared the variations in the process parameters, ease of fabrication, and characterized the properties of the final dosage forms. The variation in the printing parameters, drying time, drying temperature, and needle/nozzle types on the reproducibility and uniformity of the ODFs prepared from, these two printheads were studied. Feed materials for extrusion were selected based on rheological properties, printability, and reproducibility. An optimized ODF formulation composition was kept common and utilized for comparison. RESULTS: The ODFs from pneumatic and syringe-based extrusion printheads consistently created bulk batches with little to no significant variation. Syringe-based extrusion showed high precision with identical dimensions, whereas pneumatic extrusion showed quick fabrication. The ODFs produced by both methods were highly reproducible and showed excellent film properties such as mechanical strength, disintegration, and dissolution. The ODFs showed adequate mechanical strength (>0.72 N/mm) for packaging and transport. The disintegration time was less than a minute, and quicker dissolution within 20 min. CONCLUSION: Both pneumatic and syringe-based 3D printing technologies are deemed to be potentially viable alternatives for the fabrication of personalized dosage forms such as ODFs in pharmacy and clinical settings.
Preparation and Characterization of Novel Pan-RAS Inhibitor Loaded Ultraflexible Liposomes for the Topical Prevention or Treatment of Skin Melanoma.
Dave SA, Keeton AB, Piazza GA … +1 more , Di Pasqua AJ
Pharm Res · 2025 Dec · PMID 41298982 · Publisher ↗
PURPOSE: There are no preventive and few therapeutic options for melanoma, an aggressive skin cancer, especially in situations where N-Ras mutations are present. The new pan-Ras inhibitor ADT-007 has promise for treating...
PURPOSE: There are no preventive and few therapeutic options for melanoma, an aggressive skin cancer, especially in situations where N-Ras mutations are present. The new pan-Ras inhibitor ADT-007 has promise for treating melanoma. This study aimed to prepare a topical molecular targeted drug for prevention or treatment of early-stage melanoma using ultraflexible liposomes (UFLs) dispersed in a carbomer gel. METHODS: ADT-containing UFLs were evaluated for anticancer efficacy and selectivity in vitro using melanoma cell lines and normal keratinocytes. Comparisons were made between UFLs and traditional liposomes (TL) in terms of drug release, encapsulation efficiency, and skin permeation. Permeation tests were conducted using the skin-like Strat-M membrane. Stability of UFLs was assessed at 4°C. RESULTS: UFLs exhibited enhanced ADT-007 drug release and higher encapsulation efficiency compared to TL. ADT-007 from UFL carbomer gels penetrated more readily through the Strat-M membrane than that from TL or ADT-007 alone. UFLs were incredibly stable in regard to size and encapsulation efficiency, particularly at 4°C. This combination demonstrated low cytotoxicity against human keratinocytes but high toxicity against various human melanoma cancer cells, especially those harboring N-Ras mutations. CONCLUSIONS: This study highlights the use of UFL-based gels as a promising strategy for prevention or targeted melanoma therapy by providing enhanced drug delivery, stability, and cancer cell selectivity.
Amyloid Light Chain Proteins in Cardiovascular Disease: Pathogenesis and Emerging Therapies for Cardiac Amyloidosis.
Hu H, Wang Y, Xu M
Pharm Res · 2025 Dec · PMID 41291170 · Publisher ↗
Cardiac amyloidosis caused by amyloid light chain proteins is a life-threatening manifestation of systemic amyloid light chain amyloidosis, yet it remains underrecognized. This review explores the pathogenic mechanisms u...
Cardiac amyloidosis caused by amyloid light chain proteins is a life-threatening manifestation of systemic amyloid light chain amyloidosis, yet it remains underrecognized. This review explores the pathogenic mechanisms underlying cardiac involvement in amyloid light chain amyloidosis, focusing on two key pathways: the physical disruption from extracellular amyloid deposition and direct cardiotoxicity from circulating light chains, which induce oxidative stress, mitochondrial dysfunction, and apoptosis. Emerging therapies, including cellular immunotherapies such as chimeric antigen receptor T cells and bispecific antibodies, plasma cell-directed agents, and strategies that promote amyloid fibril removal or restore cardiomyocyte function are also evaluated. Despite advances, challenges persist in managing toxicities, accelerating amyloid clearance, and validating treatments in broader populations. Future efforts should prioritize early diagnosis, optimized combination therapies, mass spectrometry-driven drug discovery, and the development of reliable human in vitro and animal models to better recapitulate disease mechanisms and facilitate therapeutic development.
Emerging Technologies and Integrated Interdisciplinary Strategies for Mitigating Protein Aggregation in Therapeutic Formulations.
Wu H, Fan Q, Zhang Z … +1 more , Ji Y
Pharm Res · 2026 Jan · PMID 41266728 · Publisher ↗
BACKGROUND: Therapeutic proteins are playing an increasingly important role in marketed drugs and clinical candidates. However, their development still faces major challenges, particularly aggregation. OBJECTIVES: This r...
BACKGROUND: Therapeutic proteins are playing an increasingly important role in marketed drugs and clinical candidates. However, their development still faces major challenges, particularly aggregation. OBJECTIVES: This review explores the recent advancements, current limitations, and future directions of new research methods for therapeutic proteins. RESULTS: Characterization techniques identify aggregation tendencies and elucidate underlying mechanisms, while computational chemistry provides microscopic insights into the aggregation process. Theoretical modeling and machine learning offer tools for predicting protein stability, enabling high-throughput screening in early formulation development. CONCLUSION: Fostering interdisciplinary collaboration will be essential. The integration of diverse approaches offers a more comprehensive understanding of protein aggregation and unlocks new opportunities for innovation in protein formulation development.
Modulation of Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Gastrointestinal Cancers by Phytochemicals.
Pandey P, Verma M, Siddiqui S … +4 more , Alkhathami AG, Saeed M, Singh A, Khan F
Pharm Res · 2025 Nov · PMID 41266727 · Publisher ↗
The purpose of this review is to provide a concise overview of phytochemicals and their possible effects on gastrointestinal (GI) malignancies via modification of the mitogen-activated protein kinase (MAPK) signaling cas...
The purpose of this review is to provide a concise overview of phytochemicals and their possible effects on gastrointestinal (GI) malignancies via modification of the mitogen-activated protein kinase (MAPK) signaling cascade. Abnormal activation of the MAPK pathway significantly contributes to GI cancer progression and is associated with various facets of cancer, including cellular proliferation, apoptosis, invasion, angiogenesis, and metastasis. Although standard medications are essential for managing GI cancers, their side effects frequently present considerable obstacles to the patient's quality of life. Thus, there is increasing emphasis on phytochemicals that are safe, non-toxic, and multitargeted properties. In recent years, phytochemicals have garnered significant interest in antitumor therapy, leveraging their multifaceted signaling regulatory actions to activate several biological mechanisms, thereby offering substantial benefits in tumor inhibition. These phytochemicals have the ability to reduce tumor development and induce cancer cell death by selectively inhibiting several components of the MAPK pathway in in vitro and in vivo GI cancer models. Thus, this review highlights the current knowledge on phytochemicals that modulate MAPK pathway in GI cancers, their mode of action along with their limitations. In conclusion, phytochemicals offer a promising strategy for addressing dysregulation of the MAPK pathway in gastrointestinal cancer, necessitating further investigation.
Fabrication and Evaluation of Thermoresponsive GPNMB-Hydrogels as an Innovative Osteogenic Therapeutic Strategy.
Czech T, Hessel E, Knowles J … +4 more , Ameha KT, Smith MA, Safadi FF, Oyewumi MO
Pharm Res · 2025 Dec · PMID 41254321 · Full text
PURPOSE: Earlier studies have reported the ability of GPNMB protein (GPNMB) to promote osteoblast differentiation and function. However, the realization of clinical potential of GPNMB in bone regeneration will require su...
PURPOSE: Earlier studies have reported the ability of GPNMB protein (GPNMB) to promote osteoblast differentiation and function. However, the realization of clinical potential of GPNMB in bone regeneration will require suitable delivery systems to overcome challenges pertaining to poor dosing and poor retention at target sites. Distribution of osteogenic therapeutics away from the desired bone regeneration sites has been linked to serious adverse effects. METHOD: We developed thermoresponsive GPNMB-hydrogels using PLA-b-PEG-b-PLA copolymer (10-30% w/v) and demonstrated the ability to undergo solution-to-gel transition at physiologically relevant temperatures. The hydrogel formulations were characterized by vial inversion techniques, dynamic light scattering, rheological assessments and bioretention studies. GPNMB loading (1-10 µg/mL) did not interfere with hydrogel's thermo-reversibility and viscoelastic behaviors as obtained from rheological strain and frequency sweep tests. RESULTS: The in-vitro release of GPNMB reflected a diffusion-controlled kinetic and is supported by hydrogel degradation pattern involving a rapid loss of the PEG units throughout the 8-week period and a delayed degradation of the PLA units. In-vivo long- and short-term safety studies, following GPNMB treatments, showed acceptable serum levels of tissue function and inflammatory markers. There were no detectable signals of ectopic bone formation. Efficacy assessment of GPNMB-hydrogel was based on in-vitro osteoblast differentiation and in-vivo bone regeneration studies in a murine calvaria defect model. CONCLUSION: The biofunctional properties of GPNMB-hydrogels were supported by enhancement of bone regeneration. Additional studies are warranted to fully examine the potential of GPNMB-hydrogel in bone regeneration using a disease model of fracture healing.
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