Enhancing Antifungal Treatment of Candida albicans with Hypericin-Loaded Nanostructured Lipid Carriers in Hydrogels: Characterization, In Vitro, and In Vivo Photodynamic Evaluation.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus Candida albicans, whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of C. albicans-induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG). METHODS: After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated. RESULTS: Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of C. albicans (p < 0.001) by 1.2 log10 for Hy.NLC-HG/PDT and 1.9 log10 for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of p < 0.001 in the number of C. albicans colonies (log) in the vaginal canal, compared to the inoculation control group. CONCLUSIONS: Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration.

Semiochemical delivery systems based on natural polymers to attract sand flies (Diptera: Psychodidae).

BACKGROUND: The successful use of semiochemicals to attract insects to traps is based on research on the most suitable compounds and their release profiles over time. Based on the group's promising results, matrices with a more adequate release profile and more eco-friendly properties for the release of 1-hexanol were developed. To use a more suitable prototype in the field, the most promising systems were added to a capsule and evaluated in a wind tunnel. Behavioral experiments were performed using the sand fly species, Lutzomyia longipalpis, to evaluate the efficacy of the proposed system. METHODS: Different delivery systems were developed by varying the polymer (gellan gum and pectin) ratio, crosslinker (aluminum chloride) concentration, and glutaraldehyde removal.The delivery systems were loaded with 1-hexanol, and their release profiles were evaluated using gravimetric analysis under ambient and high-humidity conditions. When the matrix system was placed inside a plastic container, modulations in the active release profile were observed and the system could be reused. Actid attraction behaviors of the sand fly species, Lu. longipalpis, were evaluated in a wind tunnel when exposed to 1-hexanol-loaded release systems at different times. RESULTS: Among the four formulations evaluated, System 2 (gellan gum and pectin in a 1:1 ratio with 5% aluminum chloride) exhibited the most promising release profile, with greater uniformity and longer compound release time. The maximum 1-hexanol release uniformity was achieved over a longer time, mainly every 24 h, under both ambient and high-humidity conditions. System 2 can be reused at least once with the same structure. The wind tunnel trials exhibited efficient activation and attraction of Lu. longipalpis to 1-hexanol after 24, 48, and 72 h in System 2 placed inside the capsules. CONCLUSIONS: The polymeric matrix supplemented with 1-hexanol and introduced in plastic capsules showed promising results in attracting sand flies. This system can be used as a solution for other attractive compounds as well as in other applications where their release needs to be controlled or prolonged.

Solid dispersions based on chitosan/hypromellose phthalate blends to modulate pharmaceutical properties of zidovudine.

Zidovudine (AZT) has been widely used alone or in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus. Its erratic oral bioavailability necessitates frequent administration of high doses, resulting in severe side effects. In this study, the design of mucoadhesive solid dispersions (SDs) based on chitosan (CS) and hypromellose phthalate (HP) was rationalized as a potential approach to modulate AZT physicochemical and pharmaceutical properties. SDs were prepared at different drug:polymer ratios, using an eco-friendly technique, which avoids the use of organic solvents. Particles with diameter from 56 to 73 µm and negative zeta potentials (-27 to -32 mV) were successfully prepared, achieving high drug content. Infrared spectroscopy revealed interactions between polymers but no interactions between the polymers and AZT. Calorimetry and X-ray diffraction analyses showed that AZT was amorphized into the SDs. The mucoadhesive properties of SDs were evidenced, and the control of AZT release rates from the matrix was achieved, mainly in acid media. The simple, low-cost, and scalable technology proposed for production of SDs as a carrier platform for AZT is an innovative approach, and it proved to be a feasible strategy for modulation the physico-chemical, mucoadhesive, and release properties of the drug.

Photodynamic therapy-mediated hypericin-loaded nanostructured lipid carriers against vulvovaginal candidiasis.

INTRODUCTION AND AIM: The indiscriminate use and adverse effects of the main conventional antifungal agents compromise the effectiveness of treating vulvovaginal candidiasis (VVC), mainly caused by the species Candida albicans. This study evaluated the effectiveness of photodynamic therapy (PDT) and the in vitro and in vivo anti-candida potential of the hypericin (HYP)-loaded nanostructured lipid carriers (NLC). MATERIALS AND METHODS: Empty NLC and NLC-HYP were characterized by the dynamic light scattering technique and transmission electron microscopy to evaluate the average particle size distribution and its morphologies. The in vitro inhibition photodynamic effect of the systems was tested to reduce the planktonic viability of C. albicans. The therapeutic assay photodynamic of the systems was performed to treat VVC in mice. RESULTS: Empty NLC and NLC-HYP presented values of average hydrodynamic diameter, polydispersity index, and ζ-potential from 136 to 133 nm, 0.16 to 0.22, and -18 to -30 mV, respectively, on day 30. Microscopically, the systems showed spherical morphologies and nanoscale particles. Furthermore, in the in vitro inhibition assay, the treatment of PDT with NLC-HYP (NLC-HYP+) showed a significant reduction of the C. albicans planktonic viability compared to YNB negative control after 5 min of LED light irradiation. In the in vivo therapeutic assay, the antifungal group (vaginal antifungal cream) and NLC-HYP+ evaluated in the dark and by PDT, respectively, had a significant log10 reduction in fungal burden compared to the infected group on day 8 of the VVC treatment. CONCLUSION: Due to the in vitro and in vivo anti-candida potential, PDT-mediated systems can be an effective strategy in VVC therapy.

Ionic Cross-Linking as a Strategy to Modulate the Properties of Oral Mucoadhesive Microparticles Based on Polysaccharide Blends.

Polymer blends of gellan gum (GG)/retrograded starch(RS) and GG/pectin (P) were cross-linked with calcium, aluminum, or both to prepare mucoadhesive microparticles as oral carriers of drugs or nano systems. Cross-linking with different cations promoted different effects on each blend, which can potentially be explored as novel strategies for modulating physical-chemical and mucoadhesive properties of microparticles. Particles exhibited spherical shapes, diameters from 888 to 1764 µm, and span index values lower than 0.5. Blends of GG:P cross-linked with aluminum resulted in smaller particles than those obtained by calcium cross-linking. GG:RS particles exhibited larger sizes, but cross-linking this blend with calcium promoted diameter reduction. The uptake rates of acid medium were lower than phosphate buffer (pH 6.8), especially GG:RS based particles cross-linked with calcium. On the other hand, particles based on GG:P cross-linked with calcium absorbed the highest volume of acid medium. The percentage of systems erosion was higher in acid medium, but apparently occurred in the outermost layer of the particle. In pH 6.8, erosion was lower, but caused expressive swelling of the matrixes. Calcium cross-linking of GG:RS promoted a significantly reduction on enzymatic degradation at both pH 1.2 and 6.8, which is a promising feature that can provide drug protection against premature degradation in the stomach. In contrast, GG:P microparticles cross-linked with calcium suffered high degradation at both pH values, an advantageous feature for quickly releasing drugs at different sites of the gastrointestinal tract. The high mucoadhesive ability of the microparticles was evidenced at both pH values, and the Freundlich parameters indicated stronger particle-mucin interactions at pH 6.8.

N-(2-hydroxy)-propyl-3-trimethylammonium, O-palmitoyl chitosan: Synthesis, physicochemical and biological properties.

Two samples of N-(2-hydroxy)-propyl-3-trimethylammonium, O-palmitoyl chitosan (DPCat) with different average degrees of quaternization named as DPCat35 (DQ¯ = 35%) and DPCat80 (DQ¯ = 80%), were successfully synthesized by reacting glycidyltrimethylammonium chloride (GTMAC) with O-palmitoyl chitosan (DPCh) derivative (DS¯ = 12%). Such amphiphilic derivatives of chitosan were fully water-soluble at 1.0 < pH < 12.0 and showed significant electrostatic stability enhancement of a self-assembly micellar nanostructure (100-320 nm) due to its positively-charged out-layer. In vitro mucoadhesive and cytotoxicity essays toward healthy fibroblast cells (Balb/C 3T3 clone A31 cell), human prostate cancer (DU145) and liver cancer (HepG2/C3A) cell lines revealed that the biological properties of DPCat derivatives were strongly dependent on DQ¯. Additionally, DPCat35 had better interactions with the biological tissue and with mucin glycoproteins at pH 7.4 as well as exhibited potential to be used on the development of drug delivery systems for prostate and liver cancer treatment.

Nanostructured polyelectrolyte complexes based on chitosan and sodium alginate containing rifampicin for the potential treatment of tuberculosis.

Nanostructured polyelectrolyte complexes (nano PECs) were obtained by polyelectrolyte complexation technique from chitosan (CS) and sodium alginate (SA). Different polymer proportions were tested, as well as the addition order and homogenization type, to assess the influence on the nano PECs characteristics. The spherical shape and nanometric scale of the systems were observed by scanning electron microscopy (SEM). Nano PECs size, PDI, and zeta potential (ZP) ranged from 252 to 616 nm, from 0.22 to 0.73 and -50 to 30 mV, respectively. The increase of polymer proportion and the ultra-turrax homogenization led to the enlargement of particles size and PDI. However, no influence was observed on the ZP. The NP1s-Rb and NP4s-Rb, obtained through the sonicator with rifampicin (RIF) added before the CS and SA complexation, were selected due to the most promising characteristics of diameter (301 and 402 nm), PDI (0.27 and 0.26), and RIF incorporation (78 and 69%). The release profiles of RIF incorporated in both nano PECs were similar, with a sustained release of the drug for 180 min in phosphate buffer pH 7.2. The Weibull and the Korsmeyer-Peppas models better describe the RIF release from NP1s-Rb and NP4s-Rb, respectively, demonstrating that the release process was driven by different mechanism according to the particle composition. The nano PECs were lyophilized to prolong it stability and for possible nebulization. The addition of dextrose to the system allowed for resuspension after lyophilization. Therefore, with the results obtained, the incorporation of RIF in nano PECs based on CS and SA presents a promising system for the treatment of tuberculosis.

Computational and experimental approaches for chitosan-based nano PECs design: Insights on a deeper comprehension of nanostructure formation.

Nanostructured polyelectrolyte complexes (nano PECs) based on biopolymers are an important technological strategy to target drugs to the action and/or absorption site in a more effective way. In this work, computational studies were performed to predict the ionization, spatial arrangement and interaction energies of chitosan (CS), hyaluronic acid (HA), and hypromellose phthalate (HP), for the design of nano PEC carriers for methotrexate (MTX). The optimal pH range (5.0-5.5) for preparing nano PECs was selected by experimental and computational methodologies, favoring the polymers interactions. CS, HA, HP and MTX addition order was also rationalized, maximizing their interactions and MTX entrapment. Spherical nano-sized particles (256-575 nm, by dynamic light scattering measurement) with positive surface charge (+25.5 to +29.2 mV) were successfully prepared. The MTX association efficiency ranged from 20 to 32 %. XRD analyses evidenced the formation of a new material with an organized structure, in relation to raw polymers.

Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections.

Metronidazole (MT) is an important drug available for Helicobacter pylori infection treatment. However, in the past few years, this drug has presented effective reduction for infection control, one of the most important reasons is attributed to the reduction of retention time in the stomach environment. Mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) based on chitosan (CS) and hypromellose phthalate (HP) were rationally developed using a full factorial design (21 × 21 × 31), for the incorporation of MT based on the enhancement of the antimicrobial potential against active Helicobacter pylori, in the stomach. Different mass ratios of CS:HP (w/w) were tested, reaching the most promising ratios of 1:0.1, 1:0.5, and 1:1, and two methods of polymers addition (pouring-I and drip-II) were also evaluated. From method I, the obtained particles presented a diameter in the range of 811-1293 nm (Z-average) and a polydispersity index (PDI) between 0.47 and 0.88. By method II, there was a significant reduction in diameter and PDI to 553-739 nm and 0.23 at 0.34, respectively. The drug incorporation also resulted in a reduction in the diameter and PDI of the nano PECs. All samples showed positive zeta potential, about 20 mV, and a high percentage of MT incorporation (±95%). The method factor presented a greater influence on the nano PECs characteristics. Interactions in the system constituents were indicated by the FTIR data. Nano PECs mucoadhesiveness was observed and the composition and charge density were responsible for this phenomenon. MT dissolution evaluation showed the similarity of the dissolution profiles of free and loaded MT, in which almost 100% of the drug was in the simulated gastric medium in 120 min of testing. The in vitro antimicrobial potential against H. pylori of loaded nano PECs were measured and the minimum inhibitory concentration observed for free MT was >2000 µg/mL, while for the incorporated MT lower values were observed, showing an increase in the encapsulated MT activity.

Design of chitosan-based particle systems: A review of the physicochemical foundations for tailored properties.

Chitosan-based particles are widely proposed as biocompatible drug delivery systems with mucoadhesive and permeation enhancing properties. However, strategies on how to modulate the intended biological responses are still scarce. Considering that particle properties affect the biological outcome, the rational design of the synthesis variables should be proposed to engineer drug delivery systems with improved biological performance. The purpose of this review is to establish a deeper understanding of possible correlations between these variables and the particle properties from theoretical and experimental perspectives. The fundamental physicochemical knowledge of chitosan-based polyelectrolyte complexation and surface modification is discussed focusing on chitosan-TPP, polyelectrolyte complexes, and chitosan-surface modified PLGA or lipid particles. A set of design considerations is proposed to enable future investigation in the development of chitosan particles with modulated properties. The approach presented here contributes to the rational design of chitosan-based particles that meet different requirements for biological activities.

A novel strategy for glioblastoma treatment combining alpha-cyano-4-hydroxycinnamic acid with cetuximab using nanotechnology-based delivery systems.

Combination therapy that uses multiple drugs against different molecular targets should be considered as interesting alternatives for treating complex diseases such as glioblastoma (GBM). Drugs like alpha-cyano-4-hydroxycinnamic acid (CHC) and the monoclonal antibody cetuximab (CTX) are already explored for their capacity to act against different hallmarks of cancer. Previous reports suggest that the simultaneous use of these drugs, as a novel combining approach, might result in additive or synergistic effects. Therefore, advances in nanotechnology-based delivery systems will inevitably bring nano-mediated therapeutic gains to the proposed combination since they enable the association of different drugs into a single carrier. The current study provides indications that the new dual therapeutic strategy proposed, in association with nanotechnology, provides significative improvements when compared to the use of isolated drugs. Nanotechnological tools were employed by developing polymeric nanoparticles based on poly(lactic-co-glycolic acid) and chitosan for CHC encapsulation. Furthermore, these structures were conjugated with CTX by supramolecular forces. In summary, the encapsulation of the CHC drug into the nanoparticles increased its individual therapeutic capacity. In addition, conjugation with CTX seemed to enhance therapeutic efficacy, especially for U251 GBM cells. In conclusion, developed nanostructured delivery systems exhibited a set of favorable attributes and potential to be applied as a promising new alternative for GBM treatment. Graphical abstract .

Oral nanoparticles based on gellan gum/pectin for colon-targeted delivery of resveratrol.

Nanoparticles based on gellan gum/pectin blends were designed for colon-targeted release of resveratrol (RES). Their impact on drug release rates and permeability were evaluated using Caco-2 cell model and mucus secreting triple co-culture model. Polymeric nanoparticles (PNP) were successfully prepared by nebulization/ionotropic gelation, achieving high drug loading (>80%). PNP were spherical with a low positive charge density (+5mV) and exhibited diameters of around 330 nm. Developed PNP were able to promote effective modulation of drug release rates, so that only 3% of RES was released in acidic media over 2 h, and, in pH 6.8, the drug was released in a sustained manner, reaching 85% in 30 h. The permeability of RES-loaded PNP in the Caco-2 model was 0.15%, while in the triple co-culture model, in the presence of mucus, it reached 5.5%. The everted gut sac experiment corroborated the low permeability of RES-loaded PNP in the presence or absence of mucus and highlighted their high ability to interact with the intestinal tissue. Results indicate that the novel PNP developed in this work are safe and promising carriers for controlled delivery of RES at the colon.

Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy.

Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ±â€¯0.58% and 27.7 ±â€¯3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 µM of PS present non-toxic with >80 ±â€¯6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ±â€¯4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer.

Mucoadhesive films based on gellan gum/pectin blends as potential platform for buccal drug delivery.

Films of gellan gum:pectin blends were prepared by solvent casting method. Gellan gum:pectin mass ratios were varied (4:1; 1:1; 1:4) at different concentrations (3% or 4%) and glycerol was used as plasticizer (1 or 2%). The films were thin (18-30 µm), translucent, flexible, and homogeneous. The surface pH was suitable for buccal application. All films reached high mechanical resistance and the mucoadhesive ability of them was evidenced. High ratio of gellan gum improved the mechanical resistance and the mucoadhesion of the films as well as the control of drug release rates. The films did not disintegrate in simulate saliva up to 24 h and curcumin release could be sustained up to 12 h. The set of data evidence that the films designed in this work represent a potential platform for buccal drug delivery.

Alginate-Based Delivery Systems for Bevacizumab Local Therapy: In Vitro Structural Features and Release Properties.

Alginate-based polyelectrolyte complexes (PECs) and hydrogel were engineered as platforms for local bevacizumab (BVZ) therapy. This study provides deep comprehension on the microstructures of such systems, and their correlation with drug-release patterns. PECs and hydrogel were characterized using Fourier transform infrared spectroscopy, small-angle X-ray scattering, scanning electron microscopy, atomic force microscopy, and porosimetry. Structural investigations indicated that PECs are formed by supramolecular interactions, resulting in physically cross-linked polymer networks, whereas the BVZ-loaded hydrogel has a more compact and rigid structure, promoting better entrapment of BVZ. PECs and hydrogel were able to control the BVZ release for 4 and 8 days, respectively. Their release profiles correlated best with the Higuchi and Korsmeyer-Peppas models, respectively, indicating drug diffusion as the limiting step for drug release. Furthermore, BVZ remained biologically active in vitro after its incorporation into the hydrogel system. Together, these studies confirm that PECs and hydrogel exhibit different porous structures and physicochemical properties, making them promising platforms that allow the modulation of BVZ release meeting different requirements.

Gellan Gum/Pectin Beads Are Safe and Efficient for the Targeted Colonic Delivery of Resveratrol.

This work addresses the establishment and characterization of gellan gum:pectin (GG:P) biodegradable mucoadhesive beads intended for the colon-targeted delivery of resveratrol (RES). The impact of the polymer carrier system on the cytotoxicity and permeability of RES was evaluated. Beads of circular shape (circularity index of 0.81) with an average diameter of 914 µm, Span index of 0.29, and RES entrapment efficiency of 76% were developed. In vitro drug release demonstrated that beads were able to reduce release rates in gastric media and control release for up to 48 h at an intestinal pH of 6.8. Weibull's model correlated better with release data and b parameter (0.79) indicated that the release process was driven by a combination of Fickian diffusion and Case II transport, indicating that both diffusion and swelling/polymer chains relaxation are processes that contribute equally to control drug release rates. Beads and isolated polymers were observed to be safe for Caco-2 and HT29-MTX intestinal cell lines. RES encapsulation into the beads allowed for an expressive reduction of drug permeation in an in vitro triple intestinal model. This feature, associated with low RES release rates in acidic media, can favor targeted drug delivery from the beads in the colon, a promising behavior to improve the local activity of RES.

Mucoadhesive nanostructured polyelectrolytes complexes modulate the intestinal permeability of methotrexate.

Nanostructured polyelectrolytes complexes (nano PECs) loaded with methotrexate (MTX) were obtained by the polyelectrolyte complexation of chitosan (CS) and hyaluronic acid (HA), further incorporating hypromellose phthalate (HP). The mean diameter of nano PECs ranged from 325 to 458nm, with a narrow size distribution. Zeta potential was close to +30mV, decreasing to +21mV after the incorporation of HP, a range of values that favour the physical stability of system as the interaction with cationic biological membranes. The electrostatic interactions between the different components were indicated by the FTIR data. The mucoadhesiveness of nano PECs was demonstrated and MTX and HP influenced this property. The cell viability assays showed the biosafety of the isolated polymers and nano PECs in intestinal HT29-MTX and Caco-2 cell lines at 4h of test. The permeability values of MTX loaded in CS/HA nano PECs were 7.6 and 4-fold higher than those of CS/HA/HP nano PECS and free drug, respectively, in the Caco-2 monoculture. In mucus secreting co-culture cell model these values were 3 and 6.5 fold, respectively. Such features indicate that nano PECs developed in this work can be promising carriers for MTX in the treatment of local or systemic diseases.

A novel pH-responsive hydrogel-based on calcium alginate engineered by the previous formation of polyelectrolyte complexes (PECs) intended to vaginal administration.

This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel (hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation between alginate and PMX followed by crosslinking with calcium chloride. This system exhibited a morphology with variable pore sizes, ranging from 100 to 200 µm and adequate syringeability. The hydrogel liquid uptake ability in an acid environment was minimized by the previous PECs formation. In vitro tests evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the system was able to sustain the release up to 6 days. A burst release was observed at pH 7.4 and drug release was driven by an anomalous transport, as determined by the Korsmeyer-Peppas model. At pH 4.5, drug release correlated with Weibull model and drug transport was driven by Fickian diffusion. The calcium alginate hydrogels engineered by the previous formation of PECs showed to be a promising platform for sustained release of cationic drugs through vaginal administration.

Cellulose triacetate films obtained from sugarcane bagasse: Evaluation as coating and mucoadhesive material for drug delivery systems.

Cellulose triacetate (CTA) films were produced from cellulose extracted from sugarcane bagasse. The films were characterized using scanning electron microscopy (SEM), water vapor permeability (WVP), mechanical properties (MP), enzymatic digestion (ED), and mucoadhesive properties evaluation (MPE). WVP showed that more concentrated films have higher values; asymmetric films had higher values than symmetric films. MP showed that symmetric membranes are more resistant than asymmetric ones. All films presented high mucoadhesiveness. From the WVP and MP results, a symmetric membrane with 6.5% CTA was selected for the coating of gellan gum (GG) particles incorporating ketoprofen (KET). Thermogravimetric analysis (TGA) showed that the CTA coating does not influence the thermal stability of the particles. Coated particles released 100% of the KET in 24h, while uncoated particles released the same amount in 4h. The results highlight the CTA potential in the development of new controlled oral delivery systems.

Gellan gum microspheres crosslinked with trivalent ion: effect of polymer and crosslinker concentrations on drug release and mucoadhesive properties.

Gellan gum microspheres were obtained by ionotropic gelation technique, using the trivalent ion Al(3+). The percentage of entrapment efficiency ranged from 48.76 to 87.52% and 2(2) randomized full factorial design demonstrated that both the increase of polymer concentration and the decrease of crosslinker concentration presented a positive effect in the amount of encapsulated drug. Microspheres size and circularity ranged from 700.17 to 938.32 µm and from 0.641 to 0.796 µm, respectively. The increase of polymer concentration (1-2%) and crosslinker concentration (3-5%) led to the enlargement of particle size and circularity. However, the association of increased crosslinker concentration and reduced polymer content made the particles more irregular. In vitro and ex vivo tests evidenced the high mucoadhesiveness of microspheres. The high liquid uptake ability of the microspheres was demonstrated and the pH variation did not affect this parameter. Drug release was pH dependent, with low release rates in acid pH (42.40% and 44.93%) and a burst effect in phosphate buffer pH (7.4). The Weibull model had the best correlation with the drug release data, demonstrating that the release process was driven by a complex mechanism involving the erosion and swelling of the matrix or by non-Fickian diffusion.