Search Results (560)

Background: Betulins (betulin, betulinic acid and lupeol) demonstrated antitumor and chemopreventive activity but showed low bioavailability due to their self-aggregation in hydrophilic environments. To overcome these disadvantages, their incorporation into lipid nanoformulations (PEGylated liposomes and Lipid Nanostructured Carriers (NLCs)) has proven to represent a viable solution. Objectives: The purpose of this study is to evaluate the size and incorporation rate of these molecules in nanoformulations, as well as their delivery and metabolic fate (pure betulinic acid versus a standardized extract, TT) relative to Doxorubicin using an in vivo protocol. The investigation extended our previous in vitro investigations towards an in vivo evaluation of antitumor activity, metabolic fate and toxicity in Wistar rats bearing Walker 256 carcinoma tumors over 21 days. Since previous studies used oral or intratumor administration, this exploratory study applied intravenous administration via microbubble-assisted sonoporation, considering its higher relevance for translational studies. Methods: The delivery and metabolic fate of the parent molecules, the identification of their fragments and metabolites using UHPLC-QTOF-ESI⁺MS were investigated, along with the identification of some toxicity biomarkers in rat plasma, tumor tissues and urine. Results: Preferential accumulation of Doxorubicin in tumors was observed compared to betulinic acid and TT components, as well as their persistence in plasma or elimination in urine. Compared to PEGylated liposomes, NLC formulations (especially NLC Doxo) induced a lower survival rate, a decreased bioavailability and increased toxicity by around 20%. Conclusions: These data are a starting point and complement the contrast-enhanced imaging and histology evaluations, which may contribute to the actual knowledge about the in vivo fate of betulins. Full article

Cancer continues to pose a major global health burden, with conventional therapeutic modalities such as surgical resection, chemotherapy, radiotherapy, and immunotherapy often hindered by limited tumor specificity, substantial systemic toxicity, and the emergence of multidrug resistance. The rapid advancement of nanotechnology has introduced functionalized nanomaterials as innovative tools in the realm of precision oncology. These nanoplatforms possess desirable physicochemical properties, including tunable particle size, favorable biocompatibility, and programmable surface chemistry, which collectively enable enhanced tumor targeting and reduced off-target effects. This review systematically examines recent developments in the application of nanomaterials for cancer therapy, with a focus on several representative nanocarrier systems. These include lipid-based formulations, synthetic polymeric nanoparticles, inorganic nanostructures composed of metallic or non-metallic elements, and carbon-based nanomaterials. In addition, the article outlines key strategies for functionalization, such as ligand-mediated targeting, stimulus-responsive drug release mechanisms, and biomimetic surface engineering to improve in vivo stability and immune evasion. These multifunctional nanocarriers have demonstrated significant potential across a range of therapeutic applications, including targeted drug delivery, photothermal therapy, photodynamic therapy, and cancer immunotherapy. When integrated into combinatorial treatment regimens, they have exhibited synergistic therapeutic effects, contributing to improved efficacy by overcoming tumor heterogeneity and resistance mechanisms. A growing body of preclinical evidence supports their ability to suppress tumor progression, minimize systemic toxicity, and enhance antitumor immune responses. This review further explores the design principles of multifunctional nanoplatforms and their comprehensive application in combination therapies, highlighting their preclinical efficacy. In addition, it critically examines major challenges impeding the clinical translation of nanomedicine. By identifying these obstacles, the review provides a valuable roadmap to guide future research and development. Overall, this work serves as an important reference for researchers, clinicians, and regulatory bodies aiming to advance the safe, effective, and personalized application of nanotechnology in cancer treatment. Full article

Bacterial vaginosis (BV) is a highly prevalent vaginal infection characterized by a dysbiotic shift in the vaginal microbiota, with Gardnerella vaginalis acting as a principal pathogen. Despite its association with adverse reproductive outcomes, BV remains underexplored from both mechanistic and therapeutic standpoints. Standard antibiotic regimens frequently fail due to high recurrence rates driven by multidrug-resistant (MDR) G. vaginalis strains and biofilm formation. In response, natural compounds and nutraceuticals, owing to their intrinsic antibacterial, antibiofilm, and immunomodulatory properties, have emerged as promising candidates for alternative BV therapies. In this paper, we first compile and critically evaluate preclinical and clinical evidence on the efficacy of plant extracts, essential oils (EOs), probiotics, vitamins, proteins, fatty acids, and enzymes against G. vaginalis, emphasizing their mechanistic insights in restoring vaginal microbial balance. Next, we focus on the integration of these bioactive agents into engineered nanosystems, such as lipid-based nanoparticles (LNPs), polymeric carriers, and inorganic nanostructures, to overcome limitations related to solubility, stability, and targeted delivery. Nonetheless, comparative studies, combination therapies, and recent patent developments are discussed to highlight how naturally derived molecules can enhance antimicrobial potency and reduce cytotoxicity. In conclusion, these platforms demonstrate superior in vitro and in vivo efficacy, offering a paradigm shift in the management of BV. Key challenges include scalable manufacturing, regulatory approval, and comprehensive safety assessment. Future research should prioritize standardized nanoparticle (NP) synthesis, detailed pharmacokinetic and toxicity profiling, and well-designed clinical trials to validate nature-inspired, nanoengineered therapies against G. vaginalis-induced BV. Full article

UV radiation is responsible for acute and chronic adverse effects on the skin. In recent years, it has been shown that various phenolic acids, particularly cinnamic acid derivatives, prevent some of these effects. In the present study, the design and synthesis of three esters of ferulic acid, analogues of the octyl methoxycinnamate (OMC), one of the most commercially used filters, are presented. The esters were evaluated for their photoprotective activity against UVA and UVB radiation. The ester 3b exhibited an SPF of 9.22 and a λ_c value of 343.9, higher than the values of OMC (SPF value: 8.19, λ_c value: 337.7). The development and optimization of a novel encapsulation process of the synthesized esters in nanostructured lipid carriers (NLCs) and coating of the NLCs with chitosan was also performed. The optimization of the coating processes was performed using a Box–Behnken experimental design. The optimal nanosystems exhibited a size of 117.0 ± 5 nm, enhanced stability in dispersion, and 78% encapsulation efficiency. The nanoparticles were characterized by ATR/FT–IR, TGA, and TEM. Incorporation of the nanoparticle dispersions in a sunscreen formulation increased the SPF factor of the formulation up to 48%. The esters and nanosystems also showed a satisfactory ability to inhibit the peroxidation of linoleic acid (AAPH induced lipid peroxidation assay) (74–91% inhibition). Full article

Ginsenosides, the primary bioactive components of Panax ginseng, have demonstrated significant immunomodulatory potential. While major ginsenosides have been extensively studied, rare ginsenosides produced through deglycosylation, heating, and steaming show enhanced biological activities with improved bioavailability. This review aimed to comprehensively analyze the immunomodulatory mechanisms, structure-activity relationships (SARs), therapeutic applications, and clinical translation strategies of five emerging rare ginsenosides: F1, Rg5, Rk1, Rh1, and Rg2. We conducted a comprehensive literature review examining the production methods, immunological effects, molecular mechanisms, pharmacokinetics, safety profiles, and clinical applications of these five compounds. Analysis focused on chemical structures, immune cell modulation, signaling pathways, disease model efficacy, and bioavailability enhancement strategies. Ginsenoside F1 uniquely demonstrated immunostimulatory effects, enhancing natural killer (NK) cell cytotoxicity and macrophage phagocytosis through mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) activation. Conversely, Rg5, Rk1, Rh1, and Rg2 exhibited anti-inflammatory properties via distinct mechanisms: Rg5 through Toll-like receptor 4 (TLR4)/NF-κB inhibition, Rk1 via triple pathway modulation (NF-κB, p38 MAPK, signal transducer and activator of transcription (STAT)), Rh1 by selective p38 MAPK and STAT1 inhibition, and Rg2 through modulation of both central nervous system (neuroinflammation) and peripheral organ systems. Structure-activity analysis revealed that sugar moiety positions critically determine immunological outcomes. Crucially, advanced delivery systems including nanostructured lipid carriers, self-microemulsifying systems, and specialized liposomes have overcome the major translational barrier of poor bioavailability, achieving up to 2.6-fold improvements and enabling clinical development. Safety assessments demonstrated favorable tolerability profiles across preclinical and clinical studies. These five rare ginsenosides represent promising immunomodulatory agents with distinct therapeutic applications. F1’s unique immunostimulatory properties position it for cancer immunotherapy, while the complementary anti-inflammatory mechanisms of Rg5, Rk1, Rh1, and Rg2 offer opportunities for precision medicine in inflammatory diseases. Advanced formulation technologies and optimized production methods now enable their significant clinical translation potential, providing promising therapeutic options for immune-related disorders pending further development. Full article

Considering the world’s growing interest in health-promoting phytochemicals, the current research investigated the development of a dual-captured Ginkgo Biloba and Green Tea Extract into Collagen-Nanostructured Lipid Nanocarriers (Col-NLC-GBil-GTE) for an enhanced therapeutic efficacy against hepatic, colon or breast cancer. NLC considerably reduced cell viability; the most advanced cytotoxicity profile was determined on human colon adenocarcinoma cells (LoVo) and liver cancer cells (HepG2), e.g., tumor cell viability was 21.81% in the presence of Col-NLC-GBil-GTE, similar to that determined for Cisplatin. Col-NLC exhibited apoptosis in HepG2 and LoVo cells and no significant apoptosis induction in normal HUVECs. A 20% increase in apoptosis for HepG2 cells was registered for 100 μg/mL NLC-GBil-GTE compared to Cisplatin (Cis-Pt), e.g., a 63.4% total apoptosis for NLC-GBil-GTE versus a 52.6 apoptosis induced by 100 μg/mL of a chemotherapeutic drug. According to the cell cycle outcomes, an accumulation of hepatocyte HepG2 tumor cells in the G0/G1 phase was detected upon treatment with 100 mg/mL of NLC- and Col-NLC-GBil-GTE, simultaneously with a drastic decrease in the S phase, which may indicate a cell number reduction that enters in the division cycle. The simultaneous delivery of GBil and GTE by synchronizing their bioactivities offers several advantages; Col-NLC-GBil-GTE can be viewed as a noteworthy strategy for consideration in connection with antitumor therapeutic protocols. Full article

Background: Sustained-release (SR) formulations of non-steroidal anti-inflammatory drugs (NSAIDs) aim to prolong therapeutic activity, reduce dosing frequency, and improve patient adherence. However, currently marketed SR NSAIDs exhibit persistent limitations, including incomplete control over release kinetics, high interpatient variability in bioavailability, limited reduction in gastrointestinal adverse effects, and insufficient dose flexibility for individualized therapy. In many cases, conventional excipients and release mechanisms remain predominant, leaving drug-specific physicochemical and pharmacokinetic constraints only partially addressed. These gaps highlight the need for a comprehensive synthesis of recent technological advances to guide the development of more effective, patient-centered delivery systems. Methods: A narrative literature review was conducted using Web of Science and PubMed databases to identify original research articles and comprehensive technological studies on oral SR formulations of NSAIDs and paracetamol published between January 2020 and March 2025. Inclusion criteria focused on preclinical and technological research addressing formulation design, excipient innovations, and manufacturing approaches. Results: Sixty-four studies met the inclusion criteria, encompassing polymeric matrices (31%), lipid-based carriers (18%), microspheres/hydrogel beads/interpenetrating polymer networks (30%), nanostructured systems (11%), and hybrid platforms (10%). The most common strategies involved pH-dependent release, mucoadhesive systems, and floating drug delivery, aiming to optimize release kinetics, minimize mucosal irritation, and sustain therapeutic plasma levels. Advances in manufacturing—such as hot-melt extrusion, 3D printing, electrospinning, and spray drying—enabled enhanced control of drug release profiles, improved stability, and in some cases up to 30–50% prolongation of release time or reduction in Cmax fluctuations compared with conventional formulations. Conclusions: Recent formulation strategies show substantial potential to overcome long-standing limitations of SR NSAID delivery, with expected benefits for patient compliance and quality of life through reduced dosing frequency, better tolerability, and more predictable therapeutic effects. Nevertheless, integration of in vitro performance with pharmacokinetic and clinical safety outcomes remains limited, and the translation to clinical practice is still in its early stages. This review provides a comprehensive overview of current technological trends, identifies persisting gaps, and proposes future research directions to advance SR NSAID systems toward safer, more effective, and patient-focused therapy. Full article

Nano-carriers and dried gels were prepared to prevent the inherent flavor of Yuja (Citrus junos Tanaka) from rapidly deteriorating. The properties and stability of volatile components of Yuja dried gels were compared by using colloidal systems (nanoemulsion (NE) and nanostructured lipid carrier (NLC)), coating materials (maltodextrin (MD) and a mixture of MD and β-cyclodextrin (MD/βCD)), and drying processes (spray-drying and freeze-drying). Drying was found to have a significant effect on the particle size, moisture content, color, morphology, and volatile profiles of Yuja dried gels. Meanwhile, the stability of limonene and γ-terpinene, the main volatile components of Yuja oil, was affected by the colloidal system, coating material, and storage temperature. When Yuja oil was encapsulated by an NLC and MD/βCD coating, the degradation of limonene and γ-terpinene of Yuja dried gels was reduced during storage at 4 °C. Full article

Background: The management of triple-negative breast cancer (TNBC) remains a therapeutic challenge due to the presence of multidrug resistance (MDR) and hypoxia-induced chemoresistance, both of which substantially reduce the efficacy of conventional chemotherapy. Although certain natural compounds have shown the ability to modulate these resistance mechanisms, their clinical application is hindered by poor solubility and limited bioavailability. Among such phenolic compounds, 7-hydroxytyrosol (HTyr)—a phenolic compound from olive oil and olive leaves—has been reported to modulate hypoxia-inducible factor-1 (HIF-1). Methods: In this study, we developed hyaluronic acid (HA)-decorated solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the targeted and synergistic co-delivery of paclitaxel (PTX) and hydroxytyrosol carboxylic acid esters (C_n-HTyrCA), precursors that share the antioxidant biphenolic moiety with HTyr. Results: Among the formulations tested, SLNs of trilaurin (TL) exhibited the highest entrapment efficiency (EE%), optimal average particle size, Zeta potential, and good colloidal stability. Of the synthesized C_n-HTyrCA derivatives, C₈- and C₁₀-HTyrCA showed superior loading capacity. In vitro release profiles indicated a sustained drug release pattern for both nanoparticles. HA decoration led to a marked increase in particle size and induced a shift in surface charge, confirming successful decoration and suggesting enhanced targeting potential via HA-CD44 interaction. Cytotoxicity assays conducted on MDA-MB-231 cells showed that PTX-loaded TL-SLNs exerted enhanced antitumor activity, particularly when HA-decorated, and a synergistic effect was observed upon co-administration with SLNs loaded with C₈-HTyrCA. Conclusions: Overall, our findings support the potential of SLN as a promising strategy to overcome key resistance mechanisms in TNBC, enabling reduced chemotherapeutic dosing and improving therapeutic outcomes. Full article

Objectives: This study was designed to optimize a ceftazidime (CTZ)-loaded nanocarrier that could efficiently permeate across corneal tissues. Moreover, N-acetylcysteine (NAC) was combined with an optimized CTZ-loaded formula to augment the antimicrobial activity and facilitate the efficient healing of Pseudomonas aeruginosa-induced keratitis. Methods: Different CTZ-loaded invasomes (INVs) and CTZ-loaded nanostructured lipid carriers (NLC) were fabricated and fully characterized via the determination of the entrapment efficiency (EE%), particle size (PS), surface charge, and percentage of CTZ release. Next, NAC was added to the optimized formulae from each nanocarrier, which were further assessed through ex vivo corneal permeation and in vitro antimicrobial activity studies. Finally, an in vivo evaluation of the optimal nanocarrier in the presence of NAC was performed. Results: Both nanocarriers showed nanoscale PS with sufficient surface charges. CTZ-loaded NLC formulae showed a higher EE% range with a sustained drug release profile. Both optimized formulae showed a spherical shape and excellent stability. Moreover, the antibacterial activity and biofilm inhibition assessments confirmed the synergistic effects of NAC when combined with different CTZ-loaded nanocarriers. However, the optimized CTZ-loaded INV formula achieved higher corneal permeation and deposition compared to the optimized CTZ-loaded NLC formula. Finally, the in vivo assessment confirmed the dominance of the optimized CTZ-loaded INV formula combined with NAC, where the microbiological, histopathological, and immunohistopathological examinations showed the rapid eradication of keratitis. Conclusions: Recent strategies for the incorporation of antibiotics into nanocarriers, combined with mucolytic agents, can offer a promising platform to boost the therapeutic efficiency of antibiotics and prevent antimicrobial resistance. Full article

Curcumin has good anti-cancer and antioxidant properties. However, the poor water solubility and low bioavailability limit its application in food products. This study constructed a nanostructured lipid carrier (Cur-CLA-NLC) encapsulating curcumin using conjugated linoleic acid (CLA) as the liquid lipid and stearic acid as the solid lipid. Cur-CLA-NLC exhibits significantly enhanced bioaccessibility, antioxidant activity, and cytocompatibility. CLA, as a liquid lipid in Cur-CLA-NLC, has a dual role as a structural stabilizer and bioactive agent, and synergistically enhances antioxidant activity with curcumin. In vitro simulated digestion studies showed that the bioaccessibility of curcumin in Cur-CLA-NLC (85.7%) was much higher than that in the pure curcumin (11.7%) and curcumin lipid mixtures (9.3%). In addition, the Cur-CLA-NLC system showed anti-lipid peroxidation ability and good biocompatibility. Therefore, CLA-NLC can serve as a potential delivery system for enhancing health benefits via functional foods. Full article

Lipid-based nanocarriers are ideal drug delivery systems for transdermal administration due to their biocompatibility and biodegradability. Their lipophilicity and/or similarity to the natural lipids of the epidermis enable intermolecular interactions with the lipid membrane and therefore result in effective passage through the skin. The purpose of this review is to focus on lipid-based drug delivery nanoplatforms administered via the transdermal route by summarizing the most recent developments with the intention of fast clinical translation. Liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), ethosomes, and transfersomes exhibit ideal physicochemical characteristics and encapsulation efficiency to enhance the effectiveness of the incorporated Active Pharmaceutical Ingredients (APIs). The state of the art for fabricating transcutaneous lipid drug delivery nanoparticles and the strategies for overcoming the current obstacles, as well as the added value of novel formulations, will be discussed within the scope of Quality by Design applications. The limitations and challenges that still exist will also be considered. Full article

Plant-derived compounds offer immense therapeutic potential, yet many suffer from limited solubility, instability, and poor bioavailability, restricting their clinical application. Curcumin, a polyphenol extracted from Curcuma longa, is one such molecule, with proven antioxidant and anti-inflammatory properties. To overcome its pharmacokinetic limitations, we developed Jamamina, a sustainable nanostructured lipid carrier (NLC) system incorporating curcumin and a Natural Deep Eutectic Solvent (NaDES) phase composed of malic acid and betaine. The bioinspired formulation, based on Amazonian tucumã butter and jambu oil, achieved high encapsulation efficiency (>80%) and curcumin amorphization, enhancing solubility and colloidal stability. In vitro assays with L132 demonstrated potent antioxidant activity (DPPH), a significant reduction in pro-inflammatory cytokines (TNF-α and IL-6), and upregulation of IL-10. The system also suppressed MMP-2/9 activity and preserved cytoskeletal integrity under oxidative stress. These findings highlight Jamamina as a multifunctional, eco-friendly nanoplatform that enables the pharmacological application of plant-derived curcumin, representing a promising platform for modulating redox balance and investigating inflammation in epithelial-like contexts. Full article

Azelaic acid (AzA), a saturated dicarboxylic acid, is indicated for the treatment of acne vulgaris, rosacea, melasma, and post-inflammatory hyperpigmentation. Its antimicrobial, anti-inflammatory, and antimelanogenic properties support its use; however, its poor aqueous solubility and limited skin permeability constrain its optimal topical delivery. This review summarizes clinical evidence and advances in formulations—including conventional vehicles, polymeric/lipid nanocarriers, and deep eutectic solvent (DES) systems—to promote more effective and well-tolerated use. Across indications, 15–20% azelaic acid (AzA) formulations produced clinically meaningful improvements with mild, transient local irritation. For acne vulgaris, reductions in inflammatory and noninflammatory lesions were comparable to those of topical retinoids/adapalene, and tolerability was superior in some studies. For rosacea, the 15% gel formulation was comparable to metronidazole in reducing papules, pustules, and erythema while maintaining negligible systemic exposure. In melasma and other dyschromias, 20% cream demonstrated efficacy similar to hydroquinone, exhibiting a favorable safety profile. Advanced delivery systems, including liposomes, niosomes/ethosomes, nanostructured lipid carriers, microemulsions, nanosponges, and DES platforms, increased AzA solubilization, cutaneous deposition, and stability. This enabled dose-sparing strategies and improved adherence. Data on AzA cocrystals and ionic salts suggest additional control over release and irritation. AzA remains a versatile and well-tolerated dermatologic agent whose performance is strongly vehicle-dependent. Rational selection and engineering of carriers, particularly DES-integrated polymeric and lipid systems, can mitigate solubility and permeability limitations, enhance skin targeting, and reduce irritation in the treatment of acne and rosacea. Full article

In this work, bemotrizinol (BMTZ), a broad-spectrum UV-filter, was loaded into nanostructured lipid carriers (NLC) whose lipid matrix contained different oils (isopropyl myristate, decyl oleate, caprylic/capric triglyceride) to assess the effects of the lipid core composition on the properties of the resulting NLC. Subsequently, the effects of incorporating different concentrations of optimized BMTZ-loaded NLC on the technological properties of O/W emulsions (pH, viscosity, spreadability, occlusion factor, in vitro BMTZ release, skin permeation, and in vitro sun protection factor) were assessed. The optimized BMTZ-loaded NLC contained 3.0% w/w of isopropyl myristate and showed mean size = 190.6 ± 9.8 nm, polydispersity index = 0.153 ± 0.013, ζ-potential = −10.6 ± 1.7 mV, and loading capacity = 8% w/w. The incorporation of increasing concentrations (5, 10, 20% w/w) of optimized BMTZ loaded into emulsions provided a slight increase in spreadability, lower viscosity, and no change in pH, occlusion factor, and BMTZ release compared to emulsions containing free BMTZ. No BMTZ skin permeation was observed from all formulations. About a 20% increase in sun protection factor values was obtained for vehicles containing BMTZ-loaded NLC compared with formulations incorporating the same amount of free BMTZ. Therefore, incorporating BMTZ-loaded NLC into emulsions could be a promising strategy to develop safer and more effective sunscreen formulations. Full article