OBJECTIVE:This study aims to develop a novel biogenic nano-formulation of copper oxide nanoparticles (CuO-NPs) using the Moroccan medicinal plant Inula viscosa to address critical challenges in wound care, specifically infection risks and coagulation disorders. SIGNIFICANCE:By utilizing bioactive plant compounds as natural capping agents, this research provides an eco-friendly, multitargeted processing technology that transforms simple nanostructures into high-performance, biocompatible topical delivery systems for advanced pharmaceutical wound dressings. METHODS:CuO-NPs were biosynthesized and characterized using UV-Visible, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and Fourier transform infrared spectroscopy (FTIR) techniques. Biological characterization involved in vitro testing of anticoagulant activity, tissue regeneration potential through fibroblast proliferation (MTT assay), and hemocompatibility (Hemolysis rates). Finally, the CuO-NPs were incorporated in situ into polymeric dressings to assess antimicrobial efficacy against Staphylococcus aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa. RESULTS:Analytical characterization confirmed the successful fabrication and distinct structural integrity of the biosynthesized CuO-NPs. In vitro assays demonstrated significant anticoagulant properties, specifically modulating the intrinsic coagulation pathway. The MTT assay showed that the nano-formulation significantly accelerated fibroblast proliferation. Furthermore, hemocompatibility trials validated the material's safety yielding low hemolysis rates at low concentrations. Crucially, the engineered in situ wound dressings displayed potent, controlled antibacterial action, particularly against Gram-negative pathogens, matching positive controls. CONCLUSIONS:The developed CuO-NPs from Inula viscosa represent a sustainable, multifunctional biomaterial. Combining innovative processing with robust in vitro biological validation, this advanced formulation offers a viable technological alternative to conventional wound healing therapeutics.
OBJECTIVE:To provide a comprehensive overview of three-dimensional (3D) printing as an emerging manufacturing approach in pharmaceutical and biomedical sciences, with a focus on its role in developing advanced and personalized drug delivery systems. SIGNIFICANCE OF REVIEW:3D printing offers significant advantages over conventional manufacturing techniques by facilitating precise control over dosage, geometry, drug release and material composition. The integration of nanomaterials further improves mechanical strength, targeting capability, and therapeutic efficacy, making it highly relevant for patient-mediated healthcare solutions. KEY FINDINGS:In this review, major pharmaceutical 3D printing technologies, including inkjet printing, fused deposition modelling, stereolithography, binder jetting, and extrusion-based systems, are discussed. The applications of 3D printing technology are related to drug delivery, transdermal systems, biomedical implants, tissue engineering, bone regeneration, mucosal delivery, and microelectronic medicine. Recent advancements demonstrate the potential of nanoparticle-loaded scaffolds, smart responsive materials, microneedles, polypills, and personalised drug delivery platforms. Emerging clinical applications also indicate utility in surgical planning and patient-specific medical devices. However, challenges such as limited availability of excipients, scale-up constraints, regulatory uncertainties, drug stability concerns, and low production throughput persist. CONCLUSIONS:3D printing is rapidly advancing as a transformative platform in pharmaceutical manufacturing. Continued advancements in material science, printing precision, artificial intelligence-driven design and regulatory harmonisation are expected to overcome existing limitations, enabling the development of safer, more effective and highly customised therapeutic solutions.
OBJECTIVE:This review presents Darwinian nanomedicine as an artificial intelligence (AI)-enabled drug delivery strategy that applies Darwinian evolutionary principles as a computational and engineering analogy. Rather than implying biological evolution of nanoparticles, the framework employs iterative cycles of variation, selection, adaptation, and computational inheritance to optimize nanoparticle design through experimental feedback and AI-driven optimization. SIGNIFICANCE OF REVIEW:Conventional nanocarrier-based drug delivery systems have improved bioavailability, targeting, and therapeutic efficacy but remain static in design and limited in their ability to accommodate disease heterogeneity and variability. Darwinian nanomedicine represents a framework that integrates artificial intelligence with evolutionary optimization principles to iteratively refine nanoparticle formulations based on experimental performance rather than biological evolution. KEY FINDINGS:Recent studies demonstrate that diverse nanoparticle libraries can be iteratively screened and computationally optimized according to performance. Advances in artificial intelligence, machine learning, high-throughput screening, Bayesian optimization, and evolutionary algorithms have accelerated the identification of nanoparticle formulations with improved targeting efficiency, drug release, stability, and performance through closed-loop design-test-learn workflows. CONCLUSIONS:Darwinian nanomedicine represents a paradigm shift from static nanoparticle design toward AI-guided adaptive optimization of drug delivery systems. Importantly, the evolutionary processes described in the framework are computationally inspired rather than biological, relying on iterative engineering and experimental optimization instead of nanoparticle self-replication or genetic inheritance. Although significant challenges remain regarding scalability, reproducibility, data standardization, manufacturing, and regulatory approval, continued advances in nanotechnology and artificial intelligence may facilitate the future translation of this framework into precision medicine applications.
INTRODUCTION:This study aimed to develop and validate an Analytical Quality by Design (AQbD)-based HPTLC method for simultaneous estimation of gatifloxacin and flurbiprofen sodium in ophthalmic formulations. METHODS:Separation was achieved on silica gel 60 F254 precoated HPTLC plates using n-propanol: ammonia (8:2, v/v) as the mobile phase, with densitometric detection at 254 nm. A 32 full factorial design was employed to evaluate the effects of mobile phase composition and chamber saturation time on the Rf values of both drugs. The optimized method was validated according to ICH Q2(R1) guidelines for specificity, linearity, accuracy, precision, robustness, LOD, and LOQ. Sustainability and practicality were assessed using AGREE, GAPI, Analytical Eco-Scale, ComplexGAPI, BAGI, RAPI, and RGB12 multi-colour assessment. RESULTS:The method produced sharp, well-resolved peaks with Rf values of 0.32 ± 0.02 and 0.65 ± 0.02 for gatifloxacin and flurbiprofen sodium, respectively. Excellent linearity was observed over 600-2100 ng/band for gatifloxacin and 60-210 ng/band for flurbiprofen sodium, with correlation coefficients >0.999. Recoveries ranged from 98.30% to 99.96%, with %RSD <2%, confirming accuracy and precision. The method was successfully applied to FLUBIGAT® eye drops without interference from excipients. RGB12 multi-colour assessment yielded a Whiteness score of 80.5%. CONCLUSION:A simple, accurate, robust, and AQbD-based HPTLC method was successfully developed and validated for simultaneous determination of gatifloxacin and flurbiprofen sodium in ophthalmic formulations.
OBJECTIVE:This study focused on developing and characterizing Levofloxacin hemihydrate floating bioadhesive tablets for the treatment of Helicobacter pylori (H. pylori) infection. SIGNIFICANCE:This study demonstrates a promising gastroretentive and bioadhesive drug delivery system that enhances the effectiveness of levofloxacin in the stomach for targeted H. pylori infection treatment. METHODS:Floating bio-adhesive tablets were prepared by direct compression using sodium bicarbonate (NaHCO3) as a gas-generating agent and HPMC K4M/chitosan and carbopol 940 P/sodium alginate as release retardants and bio-adhesives. Pre-formulation flow properties were evaluated. Tablets were characterized by physicochemical parameters, bioadhesion on goat stomach mucosa, and FTIR, which confirmed drug-excipient compatibility. RESULTS:The optimized formulation (FT7) showed a buoyancy lag time of 62.59 ± 6.83 s, a total floating time of more than 12 h, a swelling index of 81.89%, and a bioadhesion strength of 28.19 ± 5.12 g. The formulation remained physically stable after three months of storage at 40 °C and 75% RH. Drug release followed a non-Fickian diffusion mechanism (n = 0.514) and best fit the Korsmeyer-Peppas model (R2 = 0.989). In vitro and in vivo mucoadhesion studies demonstrated good retention of the tablet in the rabbit stomach for over 12 h. In-vivo barium sulfate X-ray imaging further confirmed that the tablet remained floating in the stomach 12 h after oral administration. CONCLUSION:A matrix-floating bio-adhesive tablet containing levofloxacin hemihydrate was successfully developed to effectively eliminate H. pylori infection.
Objective: This study aimed to prepare an astragalus polysaccharide liposome formulation to enhance the therapeutic efficacy of astragalus polysaccharide in treating chemotherapy-induced anemia. Significance: The significance of this study lies in its ability to increase the drug exposure of astragalus polysaccharides in bone marrow tissue, thereby improving their efficacy in treating chemotherapy-induced anemia. Methods: Liposomes were prepared using the thin-film dispersion method, and their characteristics were verified. Subsequently, pharmacokinetic studies were conducted using animal experiments to calculate relevant pharmacokinetic parameters and to compare the pharmacodynamics of astragalus polysaccharide liposomes with free polysaccharides. Results: Data showed that the prepared astragalus polysaccharide liposome had a particle size of 291.23 ± 19.63 nm, a zeta potential of -37.75 ± 0.35 mV, and a polydispersity index of 0.24 ± 0.03, indicating good stability and biocompatibility. By comparing the pharmacokinetic parameters of astragalus polysaccharides and their liposomes, and analyzing the concentration changes in plasma and bone marrow, it was found that liposomes could increase the drug concentration in bone marrow. Animal experiments indicated that astragalus polysaccharide liposomes could enhance the anti-chemotherapy anemia effects of astragalus polysaccharides from multiple dimensions, including blood routine, organ index, oxidative stress factors, cell cycle, and apoptosis. Conclusion: Liposome-based formulations can prolong drug circulation time and thereby enhance the passive distribution and exposure of astragalus polysaccharides in the bone marrow, strengthening their anti-chemotherapy anemia effect.
OBJECTIVE:To fabricate and characterize extrudable polymeric matrices using a combination of ethyl cellulose (EC) and two different grades of hydroxypropyl cellulose (HPC) that can provide sustained drug release of the model drug salbutamol sulfate. SIGNIFICANCE:Implementation of the Hot-Melt Extrusion (HME) technique in the fabrication of polymeric combinations that will provide ready-to-use matrices for sustained release dosage forms. METHODS:Two formulation groups were developed; each with six formulations. The first group contained EC: HPC 370,000 ratios ranging from 55.52:13.8% to 6.9:62.46%, respectively. The second group contained EC: HPC 80,000 ranging from 59.4:10% to 9.4:60%, respectively. The release profiles were determined via in vitro studies to assess the ability of matrices to prolong salbutamol release. Solid-state characterization was also performed on the raw material and representative extrudates formulations using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) and polarized light microscopy (PLM). RESULTS:The first group formulations exhibited prolonged drug release profiles that accelerated progressively as the level of HPC 370,000 increased. In contrast, the second group formulations exhibited a noticeably faster release, demonstrating that HPC 80,000 can effectively accelerate drug release through enhanced matrix erosion and water penetration. DSC and XRPD revealed that the model drug remained in its stable crystalline state even after thermal processing via HME. PLM further confirmed drug crystallinity within the extrudates. CONCLUSION:EC-HPC matrices successfully demonstrated the feasibility of using HME to prepare sustained-release matrices for salbutamol sulfate with the ability to tune drug release by varying polymer grade and ratio.
OBJECTIVE:To develop a novel, discriminatory and biopredictive bicarbonate buffer (BB)-based dissolution method to understand the behavior of oral delayed release (DR) formulations containing Mesalamine. SIGNIFICANCE:Conventional dissolutions have limitations in obtaining discrimination and predictive in vivo behavior for various DR formulations, as it does not mimic the physiological buffering. For DR formulations, functional coat opening time plays a crucial role in determining the initial drug release. BB is a dynamic system and has natural ability to gradually increase the pH due to evaporation of CO2. This was considered as an advantage to discriminate pH sensitive DR coatings. METHODS:USP-III BB dissolution condition with 10 DPM agitation was developed. Design of experiments (DoE) approach was used to study the impact of agitation and bicarbonate molarity on rate of pH change of BB. A relation of in vitro onset of release with in vivo onset of drug absorption and Cmax was established to predict the in vivo formulation behavior. RESULTS:Developed dissolution showed differences in onset of drug release for all formulations. DoE showed that agitation had significant impact on rate of pH change of BB irrespective of molarity. A strong linear correlation was obtained for in vitro drug release onset with in vivo onset of drug absorption and Cmax (R2 >0.99) at 10 DPM agitation. The % prediction error of <10 for in vivo onset of release and <4 for Cmax was observed. CONCLUSIONS:This work demonstrates that dissolution in BB is more discriminatory and biopredictive than conventional dissolutions in predicting the onset of release and Cmax for Mesalamine DR formulations.
OBJECTIVE:To enhance the solubility and dissolution rate of poorly watersoluble drug Abiraterone Acetate (ABA) by developing solid dispersions using hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF). SIGNIFICANCE:Enhancing the biopharmaceutical performance of ABA is crucial due to its extremely poor solubility and dissolution characteristics. The present study demonstrates that HPMCAS-LF-based solid dispersion effectively improves the physicochemical performance of ABA through enhanced solubility, dissolution, and in vitro drug diffusion. METHODS:Molecular dynamics (MD) simulations were conducted over 100 ns to evaluate the stability and structural behavior of the ABA-HPMCAS-LF complex, with analyses including root mean square deviation (RMSD), radius of gyration and solvent-accessible surface area. Binding free energy was measured using MM-GBSA calculations. Solid dispersions were prepared using cogrinding and solvent assisted cogrinding techniques and characterized by FTIR, PXRD, thermal analysis (TGA/DTG-DTA), SEM, and solid-state13C NMR. Solubility, in vitro dissolution, in vitro drug diffusion, hygroscopicity, and anticancer activity were assessed. RESULTS:The ABA-HPMCAS-LF complex exhibited dynamic stability, with RMSD stabilization at 6-7 Å and a binding free energy of -33.45 kcal/mol, indicating strong van der Waals, lipophilic, and Coulombic interactions. Solid dispersions demonstrated a 1.07 to 16.72-fold increase in solubility compared to pure ABA, and in vitro release enhanced drug dissolution across different media. Diffusion increased by 6.36-fold in simulated gastric fluid (SGF 1.2) and 2.55-fold in phosphate buffer (pH 6.8) relative to pure ABA. CONCLUSION:The solid dispersion of ABA with HPMCAS-LF significantly improved solubility, dissolution, and diffusion, highlighting its potential for enhanced oral bioavailability and improved therapeutic outcomes.
OBJECTIVE:This study aimed to investigate the effects of mill type and process parameters on granule and tablet quality attributes during roller compaction and to develop a design space for optimizing granule flowability and tablet tensile strength. SIGNIFICANCE:Roller compaction improves granule flowability but can reduce tabletability. Mill type remains underexplored despite its potential impact on granule properties and downstream tablet performance. METHODS:Microcrystalline cellulose-based granules were prepared by roller compaction and milled using bar and knife rotors. The effects of screen size, mill speed, roll force, and mill type were evaluated using a Box-Behnken design. Granule size distribution, bed density, compressibility, flowability, granule shape, and tablet tensile strength were measured. Design space analysis was conducted using predefined criteria for angle of repose and tablet tensile strength. RESULTS:Mill type significantly interacted with process parameters, leading to distinct trends in granule size, density, compressibility, and flowability. Larger screen size and higher roll force produced coarser and denser granules, improving flowability. However, higher roll force reduced tablet tensile strength. Opposite effects of mill speed were observed between the two rotor types, which may be associated with differences in milling mechanism and material-retention behavior within the milling chamber. Design space analysis identified limited operating regions satisfying both flowability and tablet strength criteria, and the model-predicted conditions were experimentally verified. CONCLUSIONS:Mill type was an important factor influencing roller compaction performance and should be considered during process optimization. The formulation- and equipment-specific design space enabled simultaneous optimization of granule flowability and tablet tensile strength.
OBJECTIVE:This study aimed to design and evaluate pH-sensitive pellets loaded with 5-aminosalicylic acid (5-ASA) for targeted colon delivery in ulcerative colitis (UC) therapy. SIGNIFICANCE:The proposed formulation leverages glyceryl monooleate (GMO) and linoleic acid (LA) as liquid crystal precursors to achieve site-specific drug release. METHODS:Liquid crystal nanoparticles (LCNPs) were prepared from a GMO bulk phase using a top-down method, with LA added for pH sensitivity. The formulations were then evaluated for drug loading, encapsulation efficiency, and structure by polarized light microscopy, with drug release tested at pH 1.2 and 6.8. The LCNPs dispersions were then used to make pellets using the extrusion-spheronisation technique. Drug-excipient interactions were examined by FTIR and DSC. The pellet formulations were finally tested in a rat ulcerative colitis (UC) model by comparing colon damage scores across treatment groups. RESULTS:The pH-sensitive pellets containing LCNPs exhibited a uniform morphology, desirable aspect ratio, and sufficient mechanical strength. The in vitro release profile demonstrated a 5.7-fold higher drug release at pH 6.8 compared to pH 1.2. This targeted release was ascribed to a pH-triggered phase transition of the LA and electrostatic repulsion between the ionized drug and the carrier. The in vivo results confirmed that the pH-sensitive pellets elicited the most pronounced and statistically significant (p < 0.05) reduction in colon damage scores. CONCLUSION:The developed pellet system, which encapsulates 5-ASA within GMO/LA-based liquid crystal nanoparticles, presents a highly promising platform for targeted drug delivery in the treatment of ulcerative colitis.
OBJECTIVE:The objective of the present study was to develop, optimize, and evaluate a chitosan (CS)-based hydrogel incorporating rutin for localized drug-delivery. SIGNIFICANCE:Rutin, a naturally occurring flavonoid, possesses significant antioxidant, anti-inflammatory, and anticancer properties. However, its therapeutic applications are limited due to poor solubility and low bioavailability. The development of a CS-based injectable hydrogel system offers a promising strategy for enhancing localized delivery, improving drug retention, and achieving release at the target site. METHODS:Box-Behnken Design (BBD) was employed for optimization, where CS concentration (A) and β-Gly concentration (B) were selected as critical material attributes (CMAs), and stirring speed (C) was selected as a critical process parameter (CPP). The hydrogel formulations were evaluated based on parameters including gelation time and swelling ratio. Additionally, rheological properties and in vitro drug-release studies were performed to assess formulation performance. RESULTS:BBD identified an optimized formulation comprising 1.8% w/v CS, 35% w/v β-Gly, and a stirring speed of 460 rpm, which produced a hydrogel with a gelation time of 148 ± 1.1 s and a swelling ratio of 134.45% ± 1.4%. The experimental responses showed close agreement with the predicted values, confirming the robustness of the optimization model. The optimized hydrogel exhibited shear-thinning behavior suitable for injection and achieved approximately 86% cumulative rutin release over 24 h. Drug-release followed the Korsmeyer-Peppas model, indicating a combined diffusion and polymer relaxation mechanism. CONCLUSIONS:The QbD-based BBD approach enabled the efficient optimization of an injectable thermosensitive CS-based hydrogel system for localized delivery of rutin. The formulation exhibited desirable physicochemical and rheological properties along with controlled drug-release behavior. This hydrogel system represents a promising approach for enhancing the therapeutic efficacy of rutin in localized treatment applications.
OBJECTIVES:To evaluate a proprietary phospholipid-based self-nanoemulsifying CoQ10 delivery system using an integrated multi-compartment framework encompassing plasma pharmacokinetics, erythrocyte uptake, tissue distribution, and distribution-based indicators consistent with a possible contribution of intestinal lymphatic transport. SIGNIFICANCE:Current CoQ10 SNEDDS studies primarily assess plasma bioavailability, with limited evidence regarding intracellular delivery, tissue distribution, or absorption pathway modulation. This study extends evaluation beyond plasma-only metrics toward mechanistic, distribution-informed pharmacokinetics. METHODS:The formulation was characterized for droplet size, zeta potential, and drug loading after aqueous reconstitution. Cellular metabolic activity was assessed in Caco-2 cells using the MTT assay. In vivo pharmacokinetic and tissue-distribution studies were performed in Sprague-Dawley rats administered a single oral dose of crystalline CoQ10 or the phospholipid-based SNEDDS (30 mg/kg; n = 3/group) in this exploratory, hypothesis-generating study. Plasma, erythrocyte, and tissue CoQ10 concentrations were quantified by HPLC. RESULTS:The SNEDDS formed a stable nanoemulsion (104.2 ± 2 nm; PDI 0.221; zeta potential -52.1 mV). In Caco-2 cells, the formulation enhanced mitochondrial metabolic activity in a concentration-dependent manner. In vivo, the SNEDDS increased plasma Cmax 2.7-fold and AUC0-24 h 1.5-fold versus crystalline CoQ10 (relative bioavailability 149%). Erythrocyte CoQ10 concentrations and tissue deposition increased across all organs examined (1.3-4.5-fold). The liver-to-intestine concentration ratio inverted from 1.51 to 1.02, consistent with a possible contribution of intestinal lymphatic transport. Disproportionate Cmax enhancement relative to AUC indicated rate-limited absorption bypass. CONCLUSION:The formulation enhanced systemic, cellular, and tissue-level CoQ10 delivery, supporting mechanistic evaluation beyond plasma bioavailability alone. The observed tissue distribution pattern is consistent with a potential contribution of intestinal lymphatic transport, although direct confirmation requires dedicated lymphatic transport studies.
OBJECTIVE:This study aims systematic evaluation of potential drug excipient interactions and by using a multi technique analytical approach. SIGNIFICANCE:This study will help in finding out compatibility among domperidone and different excipients, and will facilitate excipients selection for development a stable formulation of ODTs. METHODS:Binary mixtures of domperidone and excipients which are commonly used in preparation of solid dosage forms were prepared (1:1 w/w), with and without added moisture. Studied excipients included microcrystalline cellulose, Tablettose-80 (spray-dried lactose), croscarmellose sodium, magnesium stearate, and aspartame. Samples were subjected to higher temperature and relative humidity (45 °C and 75% RH) for 90 days, as per ICH guidelines. Samples were analyzed at regular interval for drug content (by high-performance liquid chromatography), chemical interaction (by Fourier transform infrared [FTIR] spectroscopy), solid state characterization (by differential scanning calorimetry and powder X-ray diffraction [XRD]), and moisture uptake (by Karl Fischer titration). RESULTS:Drug content of all the samples remained within the range of 95%-105% throughout the study. FTIR spectra showed absence of chemical interactions as all the functional groups remained unchanged. Characteristic melting endotherm was observed in DSC thermograms. XRD analysis showed same crystallinity and polymorphic transitions were not observed. Depending upon their physicochemical properties, excipient showed different levels of hygroscopicity. Highest water sorption was observed with croscarmellose sodium and lactose whereas magnesium stearate remained non hygroscopic. Moisture uptake study showed that chemical or solid-state stability of domperidone was not affected by exposure to high relative humidity. CONCLUSIONS:Domperidone exhibited robust chemical and physical stability across all excipient environments tested. While excipient hygroscopicity varied significantly, no incompatibilities were detected that would limit formulation development of ODTs.
OBJECTIVE:This study aimed to develop rizatriptan (RZT) benzoate orally disintegrating tablets (ODTs), used in migraine treatment, using various excipients and, in particular, super-disintegrants, through the direct compression method, and to compare them with a commercial product (Maxalt® RPD). SIGNIFICANCE:Migraine is a common disease that affects quality of life. ODTs are the preferred dosage form due to their rapid effect and patient compliance. In this study, ODTs with rapid disintegration time, rapid release, and high porosity were developed using superdisintegrant for RZT. METHODS:ODT formulations were prepared by direct compression method using superdisintegrants such as Ludiflash®, Ludipress®, and Pharmaburst™ along with other excipients. Disintegration time and in vitro dissolution tests were performed and compared with Maxalt® RPD. Furthermore, the porosity, water absorption rate, wetting time, and surface morphology of the tablets were also examined. The interactions between RZT and excipients were investigated using DSC and XRD studies. RESULTS:ODT formulations containing Ludiflash® and Pharmaburst™ were found to be the most suitable according to their disintegration time, dissolution profiles. It was observed from the dissolution profile of the commercial product that 100% of the drug was dissolved within 3 min. This is thought to be due to Maxalt® RPD being manufactured by lyophilization. A highly porous structure was clearly observed on the surface of ODTs. There was no interaction between RZT and excipients. CONCLUSION:As a result, ODT formulation of RZT, used in the treatment of migraine, has been successfully developed.
OBJECTIVE:This review summarizes recent advances in pectin-based beads produced via ionotropic gelation for drug delivery, focusing on formulation variables, processing parameters, and their influence on encapsulation efficiency and drug release behavior. SIGNIFICANCE:Pectin is a low-cost, biodegradable, and biocompatible polymer with significant potential for oral drug delivery, particularly for colon-targeted systems due to its resistance to gastric conditions and degradation by colonic microbiota. Understanding how formulation and process variables affect bead properties is essential to improve reproducibility and pharmaceutical applicability. METHODS:This scoping review was conducted according to Joanna Briggs Institute methodology and PRISMA-ScR guidelines. A structured search was performed in PubMed, Scopus, and Web of Science. Studies describing the production of pectin beads via ionotropic gelation and their application in drug delivery were included. Data on formulation variables, crosslinking ions, characterization, encapsulation efficiency, and drug release were extracted and analyzed qualitatively. RESULTS:75 studies were included. Low-methoxyl pectin was the most commonly used polymer, and calcium was the predominant crosslinking ion. Polymer concentration, degree of esterification, molar mass, crosslinking conditions, co-polymers, and drying methods significantly influenced bead morphology, encapsulation efficiency, and drug release profiles. Pectin-based beads generally showed high encapsulation efficiency and pH-sensitive controlled drug release, particularly for colon-targeted delivery. CONCLUSIONS:Pectin beads produced via ionotropic gelation have demonstrated considerable potential for controlled and colon-targeted drug delivery. However, methodological variability and limited in vivo and clinical studies still limit their translation to pharmaceutical applications. Future research should focus on process standardization, Quality by Design approaches, and hybrid polymer systems.
OBJECTIVE:The objective of this review is to consolidate the role of native and recombinant spider silk in drug delivery systems. It aims to classify and compare their performance with natural and synthetic polymers, and emphasizes their potential biomedical applications. It also evaluates the limitations and technical challenges, while offering perspectives on future directions to advance the clinical practices of spider silk-based drug delivery systems. SIGNIFICANCE:Spider silk offers biocompatibility, biodegradability, high mechanical strength, low immunogenicity, and stability, making it an outstanding candidate for an advanced drug delivery system. Its unique ability to self-assemble into nanoparticles, hydrogels, and films allows for encapsulation of various drugs. KEY FINDINGS:This review highlights that recombinant silk proteins possess unique properties that make them superior to many natural and synthetic polymers for drug delivery. Recombinant production technologies allow precise control over amino acid sequences, enabling modification for targeted and sustained delivery. In drug delivery, recombinant spider silk-based systems have exhibited promise in cancer therapy, regenerative medicine, including wound healing in tissue engineering, and serving as carriers. CONCLUSION:Recombinant spider silk protein represents a versatile and biocompatible platform for advanced drug delivery systems. Although challenges in scalability and clinical translation exist, advances in engineering emphasize spider silk as a next-generation drug delivery biomaterial.
OBJECTIVE:The current investigation aims to fabricate, optimize and characterize dual-drug-loaded liposomes for the management of colon cancer. SIGNIFICANCE:Lipid-based nanocarriers are versatile nanocarriers that facilitate the loading of both hydrophilic and hydrophobic therapeutic agents. The simultaneous delivery of capecitabine (CAP) and celecoxib (CEL) is anticipated to enhance anticancer efficacy against colon cancer. METHODS:CAP-CEL-loaded liposomes (CAP-CEL-LIPs) were designed and optimized utilizing Box-Behnken Design (BBD). The optimized LIPs were characterized for particle size, polydispersity index (PDI), entrapment efficiency and morphological studies. In vitro drug release studies were conducted under both acidic and physiological conditions. Hemocompatibility was evaluated using the hemolysis assay and the stability of the LIPs was assessed over a duration of one month. RESULTS:The optimized CAP-CEL-LIPs demonstrated a mean particle size of 130 ± 2.36 nm with a PDI of 0.162 ± 0.008, showing the homogeneous particle size distribution. The encapsulation efficiency for CAP and CEL was found to be 64.96 ± 2.81% and 92.23 ± 2.22%, respectively. SEM and TEM images revealed the spherical morphology of the developed LIPs. In vitro drug release investigations revealed a controlled release profile for both drugs under both acidic and physiological conditions. The hemolysis assay showed hemolysis rate of less than 2%, thereby confirming superior blood compatibility. Stability data indicated that LIPs remained stable for one-month. The developed CAP-CEL-LIPs showed significant cytotoxic potential with enhanced cellular uptake and apoptotic activity against colon cancer cells. CONCLUSION:The engineered CAP-CEL-LIPs could be a promising platform for managing colon cancer.
OBJECTIVE:The aim of this study was to explore the design, mechanisms, and therapeutic potential of stimuli-responsive solid lipid nanoparticles (SLNs) for biofilm-targeted drug delivery, highlighting recent advances and future directions. SIGNIFICANCE OF REVIEW:Biofilm-associated infections present a significant challenge in healthcare owing to the protective extracellular matrix (EPS), which restricts antibiotic penetration and promotes biofilm resistance. SLNs have emerged as promising drug delivery systems owing to their biocompatibility, drug-loading capacity, and controlled release characteristics. Stimuli-responsive SLNs, which release drugs in response to environmental triggers such as pH, enzymes, temperature, and light, offer enhanced targeting and improved drug delivery efficiency to biofilms. Notable preclinical examples include ciprofloxacin, vancomycin, rifampin and tobramycin-all of which have been formulated in SLNs/nanostructured lipid carriers with improved antibiofilm activity versus free drug in vitro and in some in vivo models. KEY FINDINGS:Preclinical studies have demonstrated that SLN-based formulations significantly reduce biofilm biomass and enhance antibiotic efficacy against biofilm-associated infections. Stimuli-responsive SLNs facilitate deeper penetration of biofilms, thereby improving drug retention and therapeutic outcomes. However, challenges such as limited drug-loading capacity, stability, manufacturability, and clinical translation remain significant barriers to the widespread adoption of SLN-based therapies. CONCLUSIONS:Stimuli-responsive SLNs represent a promising strategy for overcoming biofilm resistance and enhancing antibiotic delivery. Although preclinical data are promising, addressing formulation challenges and improving scalability are essential for successful clinical translation. Further research on optimizing SLN design and understanding biofilm interactions will be critical for advancing SLN-based therapies for biofilm-associated infections.
