Lipid-based drug delivery systems have progressed from a simple empirical solubilization tool towards a highly precise engineered platform, capable of delivering small drug molecules, biologics and nucleic acids. Despite proven achievements reflected through the success of lipid nanoparticles-based mRNA vaccine and siRNA medicines, wider clinical translation across complex diseases still remains limited by a fragmented classification system, inaccurate IVIVC, scale-up complexity and continuously evolving and highly demanding regulatory frameworks. This review re-evaluates lipid systems by providing a functional reclassification system that directly links formulation design with biological performance and scale-up science. Instead of categorising based on simple lipid composition and structural features, lipid-based drug delivery systems are reclassified based on their primary functional roles inside the biological system. Further, this review assesses methods to strengthen IVIVC for Lipid-based drug delivery systems and how quality-by-design and emerging quality-by-digital-design approaches supported by mechanistic modelling, in-process analytical tools and machine learning can be utilised to produce a smart and robust next generation lipid carrier. Lastly, this review also highlights persistent regulatory and transitional challenges, pointing out major gaps related to standardisation, comparability and late-stage failure.
Deficiencies of vitamins D, A, E, K, B12, and Folate remain a significant public health concern, even with the broad implementation of supplementation efforts. Traditional oral vitamin formulations have low bioavailability due to poor water solubility, instability in the digestive tract, and significant first-pass metabolism. Nanocarrier-based techniques have emerged as a promising approach to overcome these problems, enabling better solubility, protecting vitamins from degradation by enzymes, and facilitating targeted transport to the intestine or lymphatic system. This article reviews current progress in nanocarrier-based strategies for vitamin delivery. The types of carriers include lipid nanoparticles, polymeric carriers, liposomes, protein and peptide-based carriers, and particulate inorganic materials. Additionally, this article examines key processes involved in nanoparticle-mediated uptake by the mucosa, absorption by the mucosa, and cellular trafficking. The focus is on the development of vitamin nanoformulations because of their importance in metabolic, skeletal, and immune system functions. The final section of the review addresses methods to improve vitamin pharmacokinetics, apart from safety and toxicity concerns, regulatory hurdles, and potential problems associated with mass production and formulation stability. In conclusion, nanocarrier-based delivery platforms for vitamins present an exciting opportunity for precision nutrition and hold the potential to enhance public health outcomes.
Irritant contact dermatitis (ICD) is a common and potentially debilitating chronic skin disorder that affects a large proportion of the worldwide population. In the present work, licofelone (LF) was incorporated into poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles to design a topical nanocarrier systems intended to boost its therapeutic impacts in treatment of ICD. To achieve this objective, LF-loaded PLGA nanoparticles (PLGANPs) were fabricated utilizing the nanoprecipitation technique, and the formulation parameters were statistically optimized utilizing a D-optimal experimental design. Three independent variables were investigated: PLGA amount (X1), poloxamer amount (X2), and poloxamer type (X3). The encapsulation efficiency (Y1: EE%), particle size (Y2: PS), polydispersity index (Y3: PDI), and zeta potential (Y4: ZP) were selected as dependent responses. The optimized formulation (P19) exhibited spherical morphology, with a particle size of 160.45 ± 0.42 nm, an encapsulation efficiency of 93.34 ± 0.26%, a PDI of 0.24 ± 0.009, and a zeta potential of -34.8 ± 0.27 mV. When incorporated into a gel, P19 displayed a sustained drug release profile and achieved 2.72-fold higher permeation across rat skin compared to a conventional LF gel. In vivo, topical application of P19 gel effectively alleviated xylene-induced ear dermatitis in mice. It markedly suppressed the inflammatory response and consequently decreased the immune expression of proinflammatory cytokines. The histopathology further confirmed a pronounced reduction in dermal edema and inflammatory cell infiltration, corroborating the biochemical findings. Collectively, these results indicate the potential of LF-loaded PLGA nanoparticles as a novel topical therapeutic system for ICD.
This study aimed to investigate the pH-dependent dissolution of the weakly basic drug carvedilol (BCS Class II) and systematically examine the influence of citric acid concentration and particle size on its release. A series of dissolution studies was conducted in media simulating the gastrointestinal pH range (1.2-7.8), specifically evaluating the effects of citric acid concentration (3% and 9%) and particle size (fine Dv50 44 μm vs. coarse Dv50 608 μm). Under acidic conditions (pH 1.2-1.6), carvedilol solubility was high and the effect of citric acid particle size was negligible (<1.3% difference). In the mid-pH range (3.8-6.5), fine citric acid particles rapidly created an acidic microenvironment (pH 3.5±0.2), enhancing carvedilol solubility 2.1-2.8-fold and improving dissolution by 3.1-15.7% compared to coarse particles; increasing the citric acid concentration from 3% to 9% reduced this particle size-dependent variability. At high pH (6.8-7.8), the effect of citric acid weakened, though coarse particles still prolonged acid release. While citric acid concentration universally enhanced carvedilol dissolution, the effect of its particle size was pH-dependent, being negligible at low pH but pronounced at higher pH, where larger particles sustained drug release more effectively.
Among ocular diseases, cataract are globally considered the primary cause of blindness. Cataract development is mainly attributed to oxidative stress, which damages epithelial lens proteins and lipids, resulting in clouding or opacification of the normally transparent lens and altering its refractive index. The widespread prevalence of environmental and pathological factors associated with increased cataract risk has heightened interest in innovative therapeutic strategies. Addressing the limitations of current pharmaceutical and surgical interventions is crucial, and the emergence of nanomedicine offers promising opportunities for more precise and effective treatment and prevention strategies compared to conventional methods. Due to their unique properties, nanoparticles have demonstrated significant potential in targeting biological systems and modulating critical physiological processes. This review highlights the potential of various traditional and nanotechnology-based therapeutic agents, including chemical compounds, antioxidants and herbal extracts showing anti-cataract activity both in vitro and in vivo. Furthermore, it explores the benefits and challenges associated with various ocular drug delivery routes for cataract treatment and prevention.
Oxidative stress is regarded as a major pathogenic key factor in chronic idiopathic pulmonary fibrosis (IPF), a disease with high mortality and an unclear cause. Gallic acid (GA) is a natural polyphenolic compound that shows significant antioxidant potential. However, its therapeutic effectiveness is limited due to low oral bioavailability, rapid metabolism, and poor aqueous solubility. To overcome such barriers, lecithin-polymer hybrid micelles (LPHM) were engineered as a nanocarrier platform for GA delivery. This study investigated the formulation and optimization of GA-loaded LPHM for pulmonary fibrosis therapy. LPHM were optimized using a D-optimal experimental design, assessing the drug amount (X1) and polymer type (X2: Pluronic® P123 or D-α-tocopheryl polyethylene glycol succinate, TPGS) on entrapment efficiency (Y1), particle size (Y2), and zeta potential (Y3). The optimized formula, comprising TPGS with 17 mg GA, showed an entrapment efficiency of 96.78 ± 1.45%, a particle size of 120.22 ± 1.45 nm, and a zeta potential of - 32.12 ± 0.97 mV. In-vitro release demonstrated a biphasic sustained-release profile. In-vivo pharmacokinetics showed a 7.35-fold increase in oral bioavailability of the optimized formula as compared to free GA. In a bleomycin-induced IPF model, the optimized formula significantly mitigated fibrotic progression, as evidenced by reductions in transforming growth factor-β, matrix metalloproteinase-7, hydroxyproline, and collagen-1. Overall, GA-loaded LPHM represent a promising oral drug delivery strategy for IPF, with broader potential in managing chronic diseases that demand sustained release and enhanced systemic exposure.
Sorafenib is an oral tyrosine kinase inhibitor which inhibits the growth of cancer cells by inhibiting several tyrosine kinase receptors taking part in the perpetuation and pathogenesis of breast tumours. Sorafenib was approved in 2005 for the treatment of liver and prostate cancers. In recent years, focused studies have explored the drugs clinical potential in breast cancer. There are several clinical trials (ongoing and completed) of sorafenib to treat metastatic breast cancer patients. Interestingly, these have shown encouraging results in particular in combination with other clinically-used drugs. However, effective clinical use has been somewhat hampered due to the drug's hydrophobicity, rapid first pass metabolism, short half-life, low oral bioavailability and side effects including hand and foot reaction as well as hypersensitivity. In attempts to overcome some of these drawbacks, nanotechnology-based delivery systems have been explored including nanocarriers like liposomes, niosomes, lipid-polymer hybrid nanoparticles, solid lipid nanocarriers, microemulsions, nanovectors and gel matrices. We will describe current state-of-the-art nanocarrier-based strategies, and discuss how such approaches can be harnessed to enhance the clinical efficacy of sorafenib for breast cancer treatment.
The administration of neurotherapeutics is severely hindered by the blood-brain barrier (BBB), which limits drug transport to the brain. Self-emulsifying drug delivery systems (SEDDS) offer a promising nanocarrier strategy for improving the solubility, transmembrane permeability across the BBB, and targeted delivery of lipophilic drugs to the central nervous system. This review highlights the formulation principles, excipient selection, and mechanistic insights into SEDDS-mediated enhancement of BBB transport. A critical evaluation of the translational potential and pharmacokinetic benefits of both oral and intranasal SEDDS is presented, along with discussions on innovations in ligand-functionalized, hybrid, and mucoadhesive SEDDS. Additionally, the application of AI/ML-driven optimization tools for preformulation design, along with physiologically based pharmacokinetic (PBPK) modelling, is discussed, and a comparative analysis of reported SEDDS compositions with AI-based formulation predictions is presented. Clinical readiness is assessed through an overview of preclinical outcomes, the patent landscape, and emerging innovation trajectories. This review also addresses key challenges, including excipient safety, scale-up hurdles, and regulatory compliance, providing expert insights into future directions for the clinical translation and optimization of SEDDS for neurotherapeutic delivery.
Conjunctivitis, keratitis, endophthalmitis, and blepharitis are among the most prevalent bacterial eye infections. Topical eye drops are convenient but often exhibit low ocular bioavailability due to anatomical and physiological barriers, which may contribute to subtherapeutic exposure and antimicrobial resistance. Besifloxacin (BFX), a fourth-generation fluoroquinolone approved exclusively for ophthalmic use, has poor aqueous solubility at tear pH and is currently marketed as a suspension requiring frequent instillation. This study aimed to develop and optimize besifloxacin-loaded nanostructured lipid carriers (BFX-NLCs) to improve delivery. BFX-NLCs were prepared by high-pressure homogenization and optimized using response surface methodology, with particle size (Z-average) as the primary response. The optimized formulation exhibited a mean particle size of ~100 nm, a polydispersity index <0.25, and an entrapment efficiency of ~75%. In vitro release in simulated tear fluid showed a sustained release profile, reaching ~65% BFX release at 24 h, best described by the Korsmeyer-Peppas model (diffusion exponent n = 0.86), indicating anomalous (non-Fickian) diffusion. The minimum inhibitory concentrations of BFX-NLC against Staphylococcus aureus ATCC 23235 and Pseudomonas aeruginosa ATCC 9027 were comparable to those of free BFX, demonstrating preservation of antimicrobial activity. BFX-NLCs were non-toxic in the Galleria mellonella larvae model and exhibited suitable viscosity and osmolality for ophthalmic use, as well as physical stability and entrapment efficiency over nine months of storage. These findings support BFX-NLCs as a promising lipid-based platform for topical ocular delivery of besifloxacin, with potential to enhance therapeutic efficacy and reduce dosing frequency in bacterial eye infections.
Antibody-drug conjugates (ADCs) have gained significant successes in the cancer treatment and are expanding rapidly into other therapeutic areas. This review outlines the integration of the analytical development and process development based on the technical challenges and control strategy of different process stages from the antibody intermediate, drug-linker intermediate, ADC drug substance (DS) to drug product (DP). The priority of analytical method development should be tailored to support the cascades of process development decision-making at early-stage, while additional analytical development for process characterization and product understanding should be planned to deliver a comprehensive analytical control strategy at late-stage for licensure. The development strategy of a few unique ADC methods including drug-antibody ratio (DAR), residual free drug quantitation, and cytotoxicity assay (bioassay) are discussed. Furthermore, the QC testing network should be strategized to allow fast speed to IND and clinical trial; the approaches including consolidated QC testing, central QC lab, one-stop shop, and conditional release may be considered and adjusted from early to late-stage product development.
Amisulpride effectively treats both positive and negative symptoms of schizophrenia. However, its poor aqueous solubility and low intestinal permeability limit oral bioavailability. This study developed chitosan-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulating amisulpride for intranasal delivery, thereby enhancing solubility, permeability, and bioavailability. Amisulpride-loaded chitosan-coated PLGA NPs were prepared using the oil-in-water emulsion-solvent evaporation method. Formulations were optimized based on particle size (PS), zeta potential (ZP), polydispersity index (PDI), entrapment efficiency (EE%), and loading capacity (LC%). The optimized formulation was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). The solubility, stability, mucoadhesion, in vitro drug release, and cytotoxicity were also evaluated. The optimized formulation (F2) had a PS of 246.13 ± 2.28 nm, PDI of 0.14 ± 0.03, ZP of 41.04 ± 1.76 mV, EE% of 77.87, and LC% of 24.64. Encapsulating the drug in the NPs increased its solubility and the stability over three months showed no significant changes in the characteristics mentioned. F2 exhibited strong mucoadhesive properties and enhanced drug release at pH 5.5 and pH 7.4, with cumulative release of 77.41% at pH 7.4 and 92.17% at pH 5.5. Cytotoxicity testing confirmed biocompatibility across 0.75-10 mg/mL. Amisulpride chitosan-coated PLGA NPs demonstrated favourable physicochemical properties, solubility, stability, controlled drug release, and mucoadhesive profile with enhanced cell viability at specific concentrations across multiple epithelial cell lines compared with the drug solution and unloaded NPs. This work highlights the promising potential of Amisulpride Chitosan-coated PLGA NPs as an innovative intranasal nanocarrier for improved schizophrenia therapy.
Surface-related critical quality attributes (CQAs) of solid oral dosage forms influence mechanical integrity, coating uniformity, imprint readability, and downstream product performance. Conventional two-dimensional visual inspection and geometry-focused three-dimensional (3D) systems primarily assess gross deviations but often lack mechanistic surface descriptors relevant to CQA interpretation. This study tested the hypothesis that integrating complementary photometric and geometric imaging modalities can enhance sensitivity to surface-related CQAs beyond single-modality inspection. A hybrid photometric-geometric reconstruction framework was developed for manufacturing-oriented surface integrity assessment. A hybrid photometric-geometric 3D reconstruction pipeline integrating photometric stereo and structured-light acquisition captured complementary local reflectance and global geometric information. Depth maps derived from both modalities were spatially aligned and fused to generate a unified surface representation. Surface descriptors, including curvature entropy and roughness metrics, were evaluated to assess surface complexity and stability. Micro-defect detectability was examined to compare reconstruction modalities under controlled experimental conditions. The hybrid reconstruction approach demonstrated improved balance between local imprint fidelity and global surface continuity compared with single-modality methods, while maintaining reproducible surface metrics across repeated sessions. Surface descriptors provided structured measures of surface variation beyond visual inspection alone. The proposed framework is positioned as a CQA-linked surface anomaly assessment tool within a Process Analytical Technology (PAT) context, rather than as a direct surrogate for traditional release testing. By enhancing mechanistic interpretation of surface variability, the approach may support risk-based PAT strategies in manufacturing. This proof-of-concept study used a small dataset (n = 4), requiring further validation with larger, diverse samples.
Lung cancer (LC) is one of the major causes of mortality due to cancer throughout the world, primarily due to difficulties in early detection and the restricted efficacy of conventional therapies. Inhalation drug delivery systems provide a potential strategy for targeted LC therapy by allowing direct deposition of drugs into the lungs, therefore improving therapeutic effectiveness and reducing systemic side effects. This review offers a comprehensive outlook on different inhalation formulations, highlighting their benefits in enhancing drug bioavailability and patient outcomes. It also explores the molecular pathways involved in LC progression and identifies critical LC treatment targets. Although substantial progress has been made in the field of LC treatment, numerous challenges hamper the clinical translation of inhalation therapeutic systems, such as formulation instability, physiological barriers, patient-specific variations, and immune responses. The strategies to deal with these problems are discussed, aiming at the modification of nanocarriers, stimuli-sensitive systems, and immunomodulatory approaches. In conclusion, the review underscores the potential of inhalation systems in the treatment of LC with special emphasis on the promise of personalized medicine and combination therapies to transform LC management.
Diabetes mellitus (Type 2, DM) is a metabolic disorder characterized by elevated blood glucose levels. Dapagliflozin (DZ) is a recently developed antidiabetic drug, but its oral use is challenged by permeability-limited absorption and first-pass metabolism, primarily via glucuronidation. The present study aims to formulate DZ-loaded bilosomes (BLS) gel for transdermal delivery to increase drug permeation and therapeutic efficacy. The DZ-BLS was formulated using the thin-film hydration method and optimized using BBD. Optimized DZ-BLS (DZ-BLS13) showed 124.2 nm of vesicle size (VS), 0.389 of PDI, 40.9 (negative) of zeta potential, and 90.76% of drug entrapment efficiency (EE). The DZ-BLS13 formulation was incorporated into chitosan gel and evaluated for various in vitro and in vivo studies. The optimized DZ-BLS13 gel formulation (DZ-BLS13G2) demonstrated favorable physicochemical properties, including an appropriate viscosity (764 ± 20.00 cP), good spreadability (228.33 ± 2.88%), and compatibility with the physiological pH (6.03 ± 0.23) of the skin. Additionally, the formulation demonstrated a sustained drug-release profile (95.17 ± 5.23%) for up to 24 h. Moreover, DZ-BLS13G2 exhibits significantly higher ex vivo rat skin permeation (1.69 ± 0.62-fold higher flux) than DZ conventional gel (DZ-G). Histopathology on excised rat skin revealed no sign of irritation. The pharmacokinetic study of DZ-BLS13G2 revealed improved bioavailability (1.88-fold and 1.48-fold) and prolonged plasma drug levels compared with DZ conventional gel and oral DZ-dispersion. Additionally, DZ-BLS13G2 exhibited significantly higher antidiabetic activity than DZ conventional gel and oral DZ-dispersion. From the findings, it can be concluded that BLS gel is a novel carrier for transdermal drug delivery to enhance therapeutic efficacy.
To mitigate the severe adverse effects associated with the systemic administration of doxorubicin (DOX), this study developed a dissolving microneedles (MN) patch loaded with doxorubicin hydrochloride (DOX-MN) for the local treatment of breast cancer. It specifically investigated the influence and underlying mechanisms of drug loading and application force on drug bioavailability. DOX-MN with intact structure and drug enrichment at the needle tips were successfully fabricated using a centrifugal micro-molding technique. Characterization confirmed the excellent mechanical strength and skin insertion capability of the MN, which dissolved rapidly and released the drug within 30 min. In vivo pharmacokinetic studies identified drug loading and application force as critical determinants of bioavailability. A high drug loading potentially created a local supersaturated state, enhancing drug penetration and achieving a relative bioavailability of 65.25%. Increasing the application force to 25 N effectively minimized drug residue on the skin surface, improving bioavailability by approximately 1.5-fold. In a 4T1 tumor-bearing mouse model, DOX-MN administration facilitated efficient drug enrichment and sustained retention at the tumor site, yielding a tumor inhibition rate (90.61%) comparable to intravenous injection. Safety assessments indicated that using a dedicated applicator significantly reduced skin irritation. This study demonstrates that optimizing drug loading and application force enables efficient local DOX delivery via MN, ensuring potent antitumor efficacy while minimizing systemic toxicity, thereby presenting a promising novel strategy for breast cancer therapy.
Rabeprazole sodium (RAB), a widely used proton pump inhibitor for treating gastroesophageal reflux disease (GERD), faces limitations in administration to pediatric and dysphagic patients due to the swallowing difficulties posed by conventional oral solid formulations. To overcome these issues, this study developed a pediatric-friendly oral RAB formulation based on a novel anion exchange resin (AER). The synthesized AER exhibited a regular spherical morphology, high porosity, and uniform particle size distribution. RAB was efficiently loaded via ion exchange to form RAB-loaded AER complexes (RAB@AER), achieving a 1.63-fold higher drug loading capacity than that of conventional resins. RAB@AER were subsequently coated with Eudragit L100 using an emulsion-solvent evaporation method, yielding microcapsules consisting of RAB-loaded AER coated by L100 (RAB@AER@L100). In vitro release studies confirmed the enteric protection of the microcapsules, with negligible drug release in acidic medium (pH 1.2) and sustained release under neutral conditions (pH 6.8). The RAB@AER@L100 enteric suspension was developed by blending the microcapsules with suitable excipients, requiring reconstitution with water before oral administration. Pharmacokinetic evaluation in rats revealed that the reconstituted suspension accelerated drug absorption (Tmax = 2 h vs. 3 h for commercial capsules) and achieved a higher peak concentration (Cmax = 3.19 vs. 2.82 μg/mL), with a comparable area under the plasma concentration-time curve (AUC0-12 h). This RAB formulation provides an alternative strategy to enhance swallowing safety and dosing convenience in vulnerable patient.
Acne vulgaris is highly prevalent and burdensome, yet conventional topical therapies are limited by poor stratum corneum penetration, follicular obstruction, low drug deposition at pilosebaceous targets, drug instability, local irritation/side effects, and variable patient adherence. This review synthesizes recent nanoformulation advances in the context of acne pathophysiology and the specific delivery barriers it creates. Lipid-based carriers (solid lipid nanocarriers (SLNs), nanostructured lipid carriers (NLCs), nanoemulsions (NEs)) and vesicular systems (liposomes, niosomes, transfersomes) can protect labile actives, enhance appendageal/follicular access, and modulate release to limit irritation, while polymeric platforms (micelles, microsponges, nanoparticles) further improve residence time and controlled delivery. Early clinical studies suggest improved lesion reduction and tolerability versus conventional vehicles; however, broader translation remains constrained by manufacturing reproducibility, scale-up, regulatory clarity, long-term safety evaluation, and cost-effectiveness. As forward-looking avenues, multifunctional co-delivery (e.g., retinoid with antibiotic/anti-inflammatory), energy-responsive adjuncts (photothermal or precision cryo as non-drug complements), and green, biodegradable materials are being explored to better tackle biological challenges such as hyperkeratinisation-related obstruction, biofilms, and irritation, while aligning with sustainability goals. Overall, nanoformulations offer a credible path to more effective, patient-centered topical acne therapy; realizing this potential will require rigorous, adequately powered clinical trials, standardized dermatopharmacokinetic endpoints, and quality-by-design scale-up to bridge laboratory promise to practice.
High flow therapy (HFT) delivers heated and humidified gas at flow rates up to 60 L/min to hypoxemic subjects, but is not conducive to simultaneous administration of pharmaceutical aerosols. Aerosol losses occur due to circuit wall impaction, environmental loss and particle growth from high humidity; resulting in poor lung delivery efficiency. This study compares two strategies for delivering dry powder aerosols during 60 L/min humidified HFT: a circuit connector (HFT-CC) which integrates directly into the standard HFT flow pathway, and an interface connector (HFT-IC) designed to bypass delivery line losses by directly injecting aerosol into the nasal prongs. Experiments were conducted using an anatomically-realistic in vitro adult nasal airway model with physiological breathing patterns, albuterol sulfate excipient enhanced growth (AS-EEG) dry powder formulation, air-jet aerosolization engine, and custom air actuation system. The HFT-CC approach improved lung delivery to 25.6% compared to existing published data (12.8%) but was limited by losses in the circuit tubing and nasal interface. The HFT-IC approach with a split nasal interface achieved 45.1% lung delivery (HFT-IC3), nearly a fourfold improvement from previously published results, by isolating aerosol flow from HFT flow and eliminating upstream losses. While nose-throat (NT) deposition in HFT-IC3 remained high (39.6%), this approach presents an attractive target for future computational and experimental optimization. These findings prove that efficient dry powder aerosol lung delivery during 60 L/min humidified HFT is achievable, laying the groundwork for translational advances in the efficient delivery of pulmonary therapies such as surfactants, antibiotics, anti-inflammatories, and antivirals during ventilatory support.
This research focuses on creating a novel Brijaluronic-based terpesomal system capable of transporting quercetin (QER) efficiently to the brain. The vesicles were fabricated through an ethanol-injection method and then refined using a structured optimization approach in Design-Expert® software. The influence of three main formulation parameters: terpene-to-drug ratio, surfactant type, and hyaluronic acid amount were evaluated. The optimization process was designed to maximize EE%, minimize VS, and maintain ZP within an acceptable stability range. The optimal formula hit a desirability target of 0.957. It achieved an 88.66% EE%, featured nano-carriers sized at 72.09 nm, and had a stable charge of - 26.5 mV. Physicochemical characterization studies revealed a spherical morphology, an in-vitro release defined by a biphasic profile, and a secure structural integrity which was validated using FTIR analysis. Moreover, over the course of three months, the formulation did not degrade or change significantly, demonstrating its high degree of stability. Notably, terpesomes demonstrated a ~ 3.5-fold enhancement in antioxidant activity, reducing the IC₅₀ from 12.98 ± 0.82 µg/mL to 3.68 ± 0.20 µg/mL, representing a statistically and pharmacologically significant improvement. Radio-kinetic assessments further supported its potential for precise brain targeting. The brain/blood was highest for the optimized formulation at all-time points. Compared with the nasal QER solution, Technetium-99m ([99mTc]Tc)-QER-loaded terpesomes exhibited superior brain-targeting efficiency, as evidenced by higher AUC, shorter Tmax, and greater Cmax values in the brain. Taken together, the Brijaluronic terpesomes represent a highly promising, innovative nano-platform. This engineered system appears poised to boost the effectiveness of QER in neurotherapeutic applications.
Retinol has emerged as a star ingredient in the cosmetics industry owing to its remarkable skincare efficacy. However, its major limitations-high irritation potential and chemical instability-necessitate further improvement. We developed a liposome primarily composed of glyceryl monooleate and poloxamer (F127). By hybridizing this with a binary alcohol system comprising a 1:1 (v/v) mixture of propylene glycol and dipropylene glycol, an ethosome (ES) capable of efficiently encapsulating retinol was obtained. Retinol-loaded ES (Ret-ES) was further modified with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS@Ret-ES), thereby optimizing particle size distribution and drug loading capacity. Increasing the binary alcohol concentration from 10 to 30% caused TPGS@Ret-ES hydrated particle size to sharply decrease from 100 to 50 nm, without significant changes in drug loading or encapsulation efficiency. Compared with retinol aqueous solutions, TPGS@Ret-ES substantially reduced degradation rates at room temperature while maintaining excellent particle size stability. Additionally, incorporating antioxidants tocopheryl acetate and Irganox 1010 further improved chemical stability. Notably, TPGS@Ret-ES simultaneously enhanced transdermal drug permeation and skin retention, with no significant irritation observed following repeated application to the same skin site in guinea pigs. In conclusion, ES represents a highly promising topical delivery carrier, and TPGS@Ret-ES shows considerable potential as a novel formulation for retinol.