Interactions of human serum albumin with phosphate and Tris buffers: impact on paclitaxel binding and nanoparticles self-assembly.

AIM: To investigate the conformational changes in human serum albumin (HSA) caused by chemical (CD) and thermal denaturation (TD) at pH 7.4 and 9.9, crucial for designing controlled drug delivery systems with paclitaxel (PTX). METHODS: Experimental and computational methods, including differential scanning calorimetry (DSC), UV-Vis and intrinsic fluorescence spectroscopy, mean diameter, polydispersity index (PDI), ζ-potential, encapsulation efficiency (EE), in vitro release and protein docking studies were conducted to study the HSA denaturation and nanoparticles (NPs) preparation. RESULTS: TD at pH 7.4 produced smaller NPs (287.1 ± 12.9 nm) than CD at pH 7.4 with NPs (584.2 ± 47.7 nm). TD at pH 9.9 exhibited high EE (97.3 ± 0.2%w/w) with rapid PTX release (50% within 1h), whereas at pH 7.4 (96.4 ± 2.1%w/w), release only 40%. ζ-potentials were around -30 mV. CONCLUSION: Buffer type and pH significantly influence NP properties. TD in PBS at pH 7.4, provided optimal conditions for a stable and efficient drug delivery system.

Development of a cationic bacterial cellulose film loaded with anionic liposomes for prolonged release of oxacillin in wound dressing applications.

Dressings should protect wounds, promote healing, absorb fluids, and maintain moisture. Bacterial cellulose is a biopolymer that stands out in biomaterials due to its high biocompatibility in several applications. In the area of dressings, it is already marketed as an alternative to traditional dressings. However, it lacks any intrinsic activity; among these, the need for antimicrobial activity in infected wounds stands out. We developed a cationic cellulose film by modifying cellulose with 1-(5-carboxypentyl)pyridin-1-ium bromide, enhancing its wettability (contact angle: 26.6°) and water retention capacity (2714.37 %). This modified film effectively retained oxacillin compared to the unmodified control. Liposomal encapsulation further prolonged oxacillin release up to 11 days. Both oxacillin-loaded films and liposomal formulations demonstrated antimicrobial activity against Staphylococcus aureus. Our findings demonstrate the potential of chemically modified cellulose as a platform for controlled anionic antibiotics and/or their formulations delivery in wound care.

Exploration of moisture activated dry granulation for the development of gastroretentive tablets aided by SeDeM diagram.

Moisture activated dry granulation (MADG) is an attractive granulation process. However, only a few works have explored modified drug release achieved by MADG, and to the best of the authors knowledge, none of them have explored gastroretention. The aim of this study was to explore the applicability of MADG process for developing gastroretentive placebo tablets, aided by SeDeM diagram. Floating and swelling capacities have been identified as critical quality attributes (CQAs). After a formulation screening step, the type and concentration of floating matrix formers and of binders were identified as the most relevant critical material attributes (CMAs) to investigate in ten formulations. A multiple linear regression analysis (MLRA) was applied against the factors that were varied to find the design space. An optimized product based on principal component analysis (PCA) results and MLRA was prepared and characterized. The granulate was also assessed by SeDeM. In conclusion, granulates lead to floating tablets with short floating lag time (<2 min), long floating duration (>4 h), and showing good swelling characteristics. The results obtained so far are promising enough to consider MADG as an advantageous granulation method to obtain gastroretentive tablets or even other controlled delivery systems requiring a relatively high content of absorbent materials in their composition.

Efficacy and safety of a 0.05 % nanoencapsulated imiquimod hydrogel for the treatment of actinic cheilitis: Drug release analysis and clinical study.

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC.

Exploring the Dissolution, Solid-state Properties, and Long-term Storage Stability of Cryoprotectant-free Fenbendazole Nanoparticles.

Fenbendazole is an antiparasitic drug widely used in veterinary medicine to treat parasitic infections caused in animals like cattle, horses, sheep, and dogs. Recently, it has been repositioned as a potential alternative for cancer treatment. However, it is a highly hydrophobic molecule (0.9 ug/mL), which can compromise its dissolution rate and absorption. Thus, this work aimed to apply a nanotechnological approach to improve drug solubility and dissolution performance. Fenbendazole nanoparticles stabilized by different poloxamers were obtained by lyophilization without cryoprotectants. The behavior of the drug in the solid state was analyzed by X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The nanosystems were also evaluated for solubility and dissolution rate. A long-term stability evaluation was performed for three years at room temperature. The yields of the lyophilization ranged between 75 and 81% for each lot. The nanoparticles showed a submicron size (< 340 nm) and a low polydispersity depending on the stabilizer. The physicochemical properties of the prepared systems indicated a remarkable amorphization of the drug, which influenced its solubility and dissolution performance. The drug dissolution from both the fresh and aged nanosystems was significantly higher than that of the raw drug. In particular, nanoparticles prepared with poloxamer 407 showed no significant modifications in their particle size in three years of storage. Physical stability studies indicated that the obtained systems prepared with P188, P237, and P407 suffered certain recrystallization during long storage at 25 °C. These findings confirm that selected poloxamers exhibited an important effect in formulating fenbendazole nanosystems with improved dissolution.

Microbicidal Polymer Nanoparticles Containing Clotrimazole for Treatment of Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) alters the innate cervicovaginal immunity, which provides an important barrier against viruses and other infections. The incidence of this disease has not decreased in the last 30 years, so effective treatments are still needed. Nanoparticles (NPs) of cellulose acetate phthalate (CAP) and clotrimazole (CLZ) were prepared by the emulsification-diffusion method. NPs were characterized using dynamic light scattering, atomic force microscopy and differential scanning calorimetry; their release profile was determined by the dialysis bag technique and mucoadhesion was evaluated with the mucin-particle method. The growth inhibition study of Candida albicans was carried out using the plate counting technique. Finally, accelerated physical stability tests of NPs were carried out, both in water and in SVF. The CAP-CLZ NPs had an average diameter of 273.4 nm, a PDI of 0.284, smooth surfaces and spherical shapes. In vitro release of CLZ from the CAP NPs was categorized with the Weibull model as a matrix system in which initial release was rapid and subsequently sustained. The inhibition of C. albicans growth by the CAP-CLZ NPs was greater than that of free CLZ, and the CAP-only NPs had a microbicidal effect on C. albicans. The NPs showed poor mucoadhesiveness, which could lead to studies of their mucopenetration capacities. An accelerated physical stability test revealed the erosion of CAP in aqueous media. A nanoparticulate system was developed and provided sustained release of CLZ, and it combined an antifungal agent with a microbial polymer that exhibited antifungal activity against C. albicans.

Self-assembled α-lactalbumin nanostructures: encapsulation and controlled release of bioactive molecules in gastrointestinal in vitro model.

BACKGROUND: Implementing encapsulation techniques is pivotal in safeguarding bioactive molecules against environmental conditions for drug delivery systems. Moreover, the food-grade nanocarrier is a delivery system and food ingredient crucial in creating nutraceutical foods. Nano α-lactalbumin has been shown to be a promissory nanocarrier for hydrophobic molecules. Furthermore, the nanoprotein can enhance the tecno-functional properties of food such as foam and emulsion. The present study investigated the nanostructured α-lactalbumin protein (nano α-la) as a delivery and controlled release system for bioactive molecules in a gastric-intestinal in vitro mimic system. RESULTS: The nano α-la was synthesized by a low self-assembly technique, changing the solution ionic strength by NaCl and obtaining nano α-la 191.10 ± 21.33 nm and a spherical shape. The nano α-la showed higher encapsulation efficiency and loading capacity for quercetin than riboflavin, a potential carrier for hydrophobic compounds. Thermal analysis of nano α-la resulted in a ΔH of -1480 J g-1 for denaturation at 57.44 °C. The nanostructure formed by self-assembly modifies the foam volume increment and stability. Also, differences between nano and native proteins in emulsion activity and stability were noticed. The release profile in vitro showed that the nano α-la could not hold the molecules in gastric fluid. The Weibull and Korsmeyer-Peppas model better fits the release profile behavior in the studied fluids. CONCLUSION: The present study shows the possibility of nano α-la as an alternative to molecule delivery systems and nutraceutical foods' formulation because of the high capacity to encapsulate hydrophobic molecules and the improvement of techno-functional properties. However, the nanocarrier is not perfectly suitable for the sustainable delivery of molecules in the gastrointestinal fluid, demanding improvements in the nanocarrier. © 2024 Society of Chemical Industry.

Evaluation of the release kinetics of hydrophilic and lipophilic compounds from lipid-polymer hybrid nanoparticles.

In disease treatment, maintaining therapeutic drug concentrations often requires multiple doses. Lipid/polymer hybrid nanoparticles (LPHNPs) offer a promising solution by facilitating sustained drug delivery within therapeutic ranges. Here, we synthesized poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with soy lecithin using nanoprecipitation and self-assembly techniques. These nanoparticles were incorporated into gelatin aerogels to ensure uniform distribution and increase the concentration. Our study focused on understanding the release kinetics of hydrophilic (gallic acid) and lipophilic (quercetin) compounds from this system. Nanoparticles exhibited hydrodynamic diameters of 100 ± 15 nm (empty), 153 ± 33 nm (gallic acid-loaded), and 149 ± 21 nm (quercetin-loaded), with encapsulation efficiencies of 90 ± 5% and 70 ± 10% respectively. Gallic acid release followed the Korsmeyer-Peppas kinetics model (n = 1.01), while quercetin showed first-order kinetics. Notably, encapsulated compounds demonstrated delayed release compared to free compounds in gelatin aerogels, illustrating LPHNPs' ability to modulate release profiles independent of the compound type. This study underscores the potential of LPHNPs in optimizing drug delivery strategies for enhanced therapeutic outcomes.

Anti-EGFR immunoliposomes for cabazitaxel delivery: From formulation development to in vivo evaluation in prostate cancer xenograft model.

Liposomes functionalized with monoclonal antibodies offer targeted therapy for cancer, boasting advantages like sustained drug release, enhanced stability, passive accumulation in tumors, and interaction with overexpressed receptors on cancer cells. This study aimed to develop and characterize anti-EGFR immunoliposomes loaded with cabazitaxel and assess their properties against prostate cancer in vitro and in vivo. Using a Box-Behnken design, a formulation with soy phosphatidylcholine, 10% cholesterol, and a 1:20 drug-lipid ratio yielded nanometric particle size, low polydispersity and high drug encapsulation. Immunoliposomes were conjugated with cetuximab through DSPE-PEG-Maleimide lipid anchor. Characterization confirmed intact antibody structure and interaction with EGFR receptor following conjugation. Cabazitaxel was dispersed within the liposomes in the amorphous state, confirmed by solid-state analyses. In vitro release studies showed slower cabazitaxel release from immunoliposomes. Immunoliposomes had enhanced cabazitaxel cytotoxicity in EGFR-overexpressing DU145 cells without affecting non-tumor L929 cells. Cetuximab played an important role to improve cellular uptake in a time-dependent fashion in EGFR-overexpressing prostate cancer cells. In vivo, immunoliposomes led to significant tumor regression, improved survival, and reduced weight loss in xenograft mice. While cabazitaxel induced leukopenia, consistent with clinical findings, histological analysis revealed no evident toxicity. In conclusion, the immunoliposomes displayed suitable physicochemical properties for cabazitaxel delivery, exhibited cytotoxicity against EGFR-expressing prostate cancer cells, with high cell uptake, and induced significant tumor regression in vivo, with manageable systemic toxicity.

Folic acid in carboxymethylcellulose/polyethylene oxide electrospun nanofibers: preparation, release and stability.

BACKGROUND: Folic acid (FA), a synthetically produced compound analogous to vitamin B9, also referred to as vitamin folate, is an essential compound in human health and faces challenges in stability during food processing. This study explores the incorporation of FA into carboxymethylcellulose (CMC) nanofibers using electrospinning to enhance its stability. RESULTS: In this study, optimization of both electrospinning and solution parameters facilitated the fabrication of nanofibers. Furthermore, incorporating FA into CMC/polyethylene oxide (PEO) nanofibers resulted in thinner fibers, with an average diameter of 88 nm, characterized by a flat shape and smooth surface. Fourier transform infrared spectroscopic analysis demonstrated substantial hydrogen bonding interactions between FA and the polar groups present in CMC. This interaction contributed to an encapsulation efficiency of 94.5%, with a yield exceeding 87%. Thermal analysis highlighted mutual interference between CMC and PEO, with FA enhancing the thermal stability and reducing the melting temperatures and enthalpies of PEO, while also increasing the reaction heats of CMC. The encapsulated FA remained stable in acidic conditions, with only 6% degradation over 30 days, demonstrating the efficacy of CMC/PEO nanofibers in safeguarding FA against acidic environments. Moreover, the nanofibers provided a protective barrier against UV radiation, thereby preserving the stability of FA. CONCLUSION: This study emphasizes the efficacy of CMC/PEO nanofibers as a protective matrix against FA degradation. The findings indicate that this innovative approach could significantly diversify the applications of FA in food fortification, addressing concerns regarding its vulnerability to temperature and hydrolysis reactions during food processing. © 2024 Society of Chemical Industry.

Doxorubicin-galactomannan nanoconjugates for potential cancer treatment.

In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH2, yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects.

Fresh Carrier for an Old Topical Local Anesthetic: Benzocaine in Nanostructured Lipid Carriers.

Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.

3D printed benznidazole tablets based on an interpolyelectrolyte complex by melting solidification printing process (MESO-PP): An innovative strategy for personalized treatment of Chagas disease.

3D printing technology is revolutionizing pharmaceuticals, offering tailored solutions for solid dosage forms. This innovation is particularly significant for conditions like Chagas disease, which require weight-dependent treatments. In this work, a formulation of benznidazole (BNZ), the primary treatment for this infection, was developed to be utilized with the Melting Solidification Printing Process (MESO-PP) 3D printing technique. Considering the limited aqueous solubility of BNZ, an interpolyelectrolyte complex (IPEC), composed of chitosan and pectin, was integrated to improve its dissolution profile. The formulations, also called inks in this context, with and without IPEC were integrally characterized and compared. The printing process was studied, the release of BNZ from 3D-prints (3DP) was exhaustively analyzed and a physiologically based pharmacokinetic model (PKPB) was developed to forecast their pharmacokinetic performance. 3DP were successfully achieved loading 25, 50 and 100 mg of BNZ. The presence of the IPEC in the ink caused a decrease in the crystalline domain of BNZ and facilitated the printing process, reaching a print success rate of 83.3 %. Interestingly, 3DP-IPEC showed accelerated release dissolution profiles, releasing over 85 % of BNZ in 90 min, while 3DP took up to 48 h for doses above 25 mg. The PBPK model demonstrated that 3DP-IPEC tablets would present high bioavailability (0.92), higher than 3DP (0.36) and similar to the commercial product. This breakthrough holds immense potential for improving treatment outcomes for neglected diseases.

Collagen-ß-cyclodextrin hydrogels for advanced wound dressings: super-swelling, antibacterial action, inflammation modulation, and controlled drug release.

A key strategy in enhancing the efficacy of collagen-based hydrogels involves incorporating polysaccharides, which have shown great promise for wound healing. In this study, semi-interpenetrating polymeric network (semi-IPN) hydrogels comprised of collagen (Col) with the macrocyclic oligosaccharide ß-cyclodextrin (ß-CD) (20-80 wt.%) were synthesised. Fourier-transform infrared (FTIR) spectroscopy confirmed the successful fabrication of these Col/ß-CD hydrogels, evidenced by the presence of characteristic absorption bands, including the urea bond band at ∼1740 cm-1, related with collagen crosslinking. Higher ß-CD content was associated with increased crosslinking, higher swelling, and faster gelation. The ß-CD content directly influenced the morphology and semi-crystallinity. All Col/ß-CD hydrogels displayed superabsorbent properties, enhanced thermal stability, and exhibited slow degradation rates. Mechanical properties were significantly improved with contents higher than ß-CD 40 wt.%. These hydrogels inhibited the growth of Escherichia coli bacteria and facilitated the controlled release of agents, such as malachite green, methylene blue, and ketorolac. The chemical composition of the Col/ß-CD hydrogels did not induce cytotoxic effects on monocytes and fibroblast cells. Instead, they actively promoted cellular metabolic activity, encouraging cell growth and proliferation. Moreover, cell signalling modulation was observed, leading to changes in the expression of TNF-α and IL-10 cytokines. In summary, the results of this research indicate that these novel hydrogels possess multifunctional characteristics, including biocompatibility, super-swelling capacity, good thermal, hydrolytic, and enzymatic degradation resistance, antibacterial activity, inflammation modulation, and the ability to be used for controlled delivery of therapeutic agents, indicating high potential for application in advanced wound dressings.

Amiodarone chewable gels as a potential appproach for paediatric congenital cardiopathies treatment: Comparison between animal and vegetal gelling agents.

The difficulty in swallowing is a frequent problem when oral solid dosage forms (conventional tablets or capsules) are administered to paediatric population or patients with dysphagia. An interesting alternative to overcome these problems are non-conventional formulations like chewable gels, commonly known as 'gummies'. Therefore, this work addresses the design, development and characterization of gummies using gelatine and pectin, for the vehiculization of the antiarrhythmic amiodarone (AMIO). Applying a Design of Experiments (DoE) approach, four gelatine (GG1-GG4) and eight pectin formulations (PG1-PG8) were developed. Considering the obtained results for responses during DoE evaluation (i.e., volume, syneresis, hardness, and gumminess), GG3 and PG8 were selected for complete characterization. Water activity, pH, drug content, texture parameters (adhesiveness, springiness, cohesiveness, and fracturability), disintegration time, in vitro dissolution, and microbiological features were evaluated. The obtained results were within the expected values for this type of formulation. The dissolution profiles showed a 94 % - 99 % of the AMIO content released for GG3 and PG8, respectively, so they could be considered suitable as immediate release dosage forms. In conclusion, the chewable gels were successfully developed and characterised, suggesting a potential means to accomplish a final prototype for the improvement of congenital cardiopathies treatment.

Development and pharmacological evaluation of liposomes and nanocapsules containing paroxetine hydrochloride.

Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.

3D printed scaffolds as delivery devices for nanocrystals: A proof of concept loading Atorvastatin with enhanced properties for sublingual route of administration.

Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of nanocrystals (NCs). Beyond the many advantages of formulating NCs, their incorporation into solid dosage forms remains a challenge that limits their use. In this work, we set out to load Atorvastatin NCs (ATV-NCs) in a delivery device by combining 3D scaffolds with an "in situ" loading method such as freeze-drying. When comparing two infill patterns for the scaffolds at two different percentages, the one with the highest NCs load was chosen (Gyroid 20 % infill pattern, 13.8 ± 0.5 mg). Colloidal stability studies of NCs suggest instability in acidic media, and therefore, the system is postulated for use as a sublingual device, potentially bypassing stomach and hepatic first-pass effects. An ad hoc dissolution device was developed to mimic the release of actives. The nanometric size and properties acquired in the process were maintained, mainly in the dissolution rate and speed, achieving 100 % dissolution of the content in 180 s. Based on these results, the proof of concept represents an innovative approach to converting NCs suspensions into solid dosage forms.

Electrochemical Characterization of the Encapsulation and Release of 5-Fluorouracil in Nanocarriers Formed from Soy Lecithin Vesicles.

5-Fluorouracil (5-FU) is an antineoplastic agent known for its low bioavailability and limited cellular penetration, often resulting in adverse effects on healthy cells. Thus, finding vehicles that enhance bioavailability, enable controlled release, and mitigate adverse effects is crucial. The study focuses on encapsulating 5-FU within soy lecithin vesicles (SLVs) and assessing its impact on the carrier's properties and functionality. Results show that incorporating 5-FU does not affect SLVs' size or polydispersity, even postlyophilization. Liberation of 5-FU from SLVs requires system disruption rather than spontaneous release, with an encapsulation efficiency of approximately 43% determined using Square Wave Voltammetry. Cytotoxicity assays on colorectal cancer cells reveal SLV-based delivery's significant efficacy, surpassing free drug solution effects with 45% cell viability after 72 h vs 73% viability. The research addresses 5-FU's limited bioavailability by creating a biocompatible nanocarrier for efficient drug delivery, highlighting SLVs as promising for targeted cancer therapy due to sustained antiproliferative effects and improved cellular uptake. The study underscores the importance of tailored drug delivery systems in enhancing therapeutic outcomes and suggests SLV/5-FU formulations as a potential advancement in cancer treatment strategies.

Self-assembly mucoadhesive beads of κ-carrageenan/sericin for indomethacin oral extended release.

Oral drug administration, especially when composed of mucoadhesive delivery systems, has been a research trend due to increased residence time and contact with the mucosa, potentially increasing drug bioavailability and stability. In this context, this study aimed to develop self-assembly mucoadhesive beads composed of blends of κ-carrageenan and sericin (κ-Car/Ser) loaded with the anti-inflammatory drug indomethacin (IND). We investigated the swelling, adhesion behaviour, and mechanical/physical properties of the beads, assessing their effects on cell viability, safety and permeation characteristics in both 2D and triple-culture model. The swelling ratio of the beads indicated pH-responsiveness, with maximum water absorption at pH 6.8, and strong mucoadhesion, increasing primarily with higher polymer concentrations. The beads exhibited thermal stability and no chemical interaction with IND, showing improved mechanical properties. Furthermore, the beads remained stable during accelerated and long-term storage studies. The beads were found to be biocompatible, and IND encapsulation improved cell viability (>70 % in both models, 79 % in VN) and modified IND permeation through the models (6.3 % for F5 formulation (κ-Car 0.90 % w/v | Ser 1.2 % w/v| IND 3.0 g); 10.9 % for free IND, p < 0.05). Accordingly, κ-Car/Ser/IND beads were demonstrated to be a promising IND drug carrier to improve oral administration while mitigating the side effects of non-steroidal anti-inflammatories.

One-step synthesis of amphiphilic copolymers PDMS-b-PEG using tris(pentafluorophenyl)borane and subsequent study of encapsulation and release of curcumin.

A series of amphiphilic block copolymer (BCP) micelles based on poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) (PEG) were synthesized by a one-step reaction in the presence of tris(pentafluorophenyl)borane (BCF) as a catalyst. The structural composition of PDMS-b-PEG (PR11) and PEG-b-PDMS-b-PEG (PR12) was corroborated by FTIR, 29Si NMR, and TGA. The BCPs were assembled in an aqueous solution, obtaining micelles between 57 and 87 nm in size. PR11 exhibited a higher (2.0 g L-1) critical micelle concentration (CMC) than PR12 (1.5 g L-1) due to the short chain length. The synthesized nano micelles were used to encapsulate curcumin, which is one of three compounds of turmeric plant 'Curcuma longa' with significant biological activities, including antioxidant, chemoprotective, antibacterial, anti-inflammatory, antiviral, and anti-depressant properties. The encapsulation efficiency of curcumin was 60% for PR11 and 45% for PR12. Regarding the release study, PR11 delivered 53% curcumin after five days under acidic conditions (pH of 1.2) compared to 43% at a pH of 7.4. The degradation products of curcumin were observed under basic conditions and were more stable at acidic pH. In both situations, the release process is carried out by breaking the silyl-ether bond, allowing the release of curcumin. PR11 showed prolonged release times, so it could be used to reduce ingestion times and simultaneously work as a nanocarrier for other hydrophobic drugs.