Design, Synthesis, Characterization, and Evaluation of the Anti-HT-29 Colorectal Cell Line Activity of Novel 8-Oxyquinolinate-Platinum(II)-Loaded Nanostructured Lipid Carriers Targeted with Riboflavin.

Colorectal cancer is occasionally called colon or rectal cancer, depending on where cancer begins to form, and is the second leading cause of cancer death among both men and women. The platinum-based [PtCl(8-O-quinolinate)(dmso)] (8-QO-Pt) compound has demonstrated encouraging anticancer activity. Three different systems of 8-QO-Pt-encapsulated nanostructured lipid carriers (NLCs) with riboflavin (RFV) were investigated. NLCs of myristyl myristate were synthesized by ultrasonication in the presence of RFV. RFV-decorated nanoparticles displayed a spherical shape and a narrow size dispersion in the range of 144-175 nm mean particle diameter. The 8-QO-Pt-loaded formulations of NLC/RFV with more than 70% encapsulation efficiency showed sustained in vitro release for 24 h. Cytotoxicity, cell uptake, and apoptosis were evaluated in the HT-29 human colorectal adenocarcinoma cell line. The results revealed that 8-QO-Pt-loaded formulations of NLC/RFV showed higher cytotoxicity than the free 8-QO-Pt compound at 5.0 µM. All three systems exhibited different levels of cellular internalization. Moreover, the hemotoxicity assay showed the safety profile of the formulations (less than 3.7%). Taken together, RFV-targeted NLC systems for drug delivery have been investigated for the first time in our study and the results are promising for the future of chemotherapy in colon cancer treatment.

Colloidal delivery of vitamin E into solid lipid nanoparticles as a potential complement for the adverse effects of anemia treatment.

Vitamin E (VitE) is one of the most important antioxidants and plays a key role in decreasing the inflammatory effects of oxidative stress caused by recurrent doses of iron administration in anemia treatment. However, VitE is poorly soluble in aqueous environments. Here, VitE encapsulation into solid lipid nanoparticles (SLN) composed of myristil myristate to improve its bioavailability was proposed. A 99.9 ± 0.1% encapsulation efficiency with a drug/lipid ratio of 500 µg/mg and 478 higher VitE solubility was obtained. The antioxidant properties of VitE after encapsulation were maintained. SLN-VitE showed a 228.2 nm mean diameter with low polidispersitivity (0.335), and negative Z potential (ζ ≈ -9.0 mV). The SLN were well-dispersed, displayed spherical and homogeneous morphology by TEM. A controlled release of VitE from SLN was found. The XRD and FTIR analyses revealed the presence of a nanostructured architecture of SLN after VitE incorporation. We probed the safety of SLN-VitE after contact with three in vitro cell models: erythrocytes, lymphocytes and HepG2 cells. The cell viability in presence of SLN, SLN-VitE, and their combinations with iron was not affected. The comet assay demonstrated that the DNA damage caused by iron administration was decrease in presence of SLN-VitE.

Prodigiosin: a promising biomolecule with many potential biomedical applications.

Pigments are among the most fascinating molecules found in nature and used by human civilizations since the prehistoric ages. Although most of the bio-dyes reported in the literature were discovered around the eighties, the necessity to explore novel compounds for new biological applications has made them resurface as potential alternatives. Prodigiosin (PG) is an alkaloid red bio-dye produced by diverse microorganisms and composed of a linear tripyrrole chemical structure. PG emerges as a really interesting tool since it shows a wide spectrum of biological activities, such as antibacterial, antifungal, algicidal, anti-Chagas, anti-amoebic, antimalarial, anticancer, antiparasitic, antiviral, and/or immunosuppressive. However, PG vehiculation into different delivery systems has been proposed since possesses low bioavailability because of its high hydrophobic character (XLogP3-AA = 4.5). In the present review, the general aspects of the PG correlated with synthesis, production process, and biological activities are reported. Besides, some of the most relevant PG delivery systems described in the literature, as well as novel unexplored applications to potentiate its biological activity in biomedical applications, are proposed.

Binary Medical Nanofluids by Combination of Polymeric Eudragit Nanoparticles for Vehiculization of Tobramycin and Resveratrol: Antimicrobial, Hemotoxicity and Protein Corona Studies.

The development of smart nanoparticles (NPs) became a trend to enhance the delivery of drugs. In the present work, Tobramycin (TB), an aminoglycoside antibiotic that displays several undesirable side effects, has been encapsulated into cationic Eudragit®E100 (E100) NPs for the treatment of infections caused by Pseudomonas aeruginosa. Combination with neutral Eudragit®NE30D (NE30D) NPs containing resveratrol (RSV), a strong natural antioxidant, increased the antimicrobial activity of TB (75% higher than free TB). NPs were stabilized with 1.0% (w/v) poloxamer 188 (P188) or poloxamer 407 (P407) as surfactants. E100 NPs showed 83.3 ± 8.5%, and 70.1 ± 2.7 encapsulation efficiency (EE) of TB with P188 and P407 coatings, respectively. The presence of NPs was confirmed by DLS and TEM studies. TB was controlled released from NPs for 6 h. Hemotoxicity tests of NPs in the range of MIC values on human blood gave negative results. Analysis of Surface Plasmon Resonance verified that NE30D/P407/RSV does not interact with plasma proteins BSA, IgG or fibrinogen, besides E100/P188/TB interact with BSA, findings that are compatible with a negligible in vivo clearance of the nanovehicles. The obtained results show a potential binary fluid composed of two NPs to highly improve the effectiveness of conventional antibiotics.

Enzymes and biopolymers. The opportunity for the smart design of molecular delivery systems.

Enzymes exhibit a tremendous potential due to the catalytic activity in response to physiological conditions and specific microenvironments. Exploiting these properties in combination with the versatility of biopolymers, a fascinating field for the rational development of a new class of "smart" delivery systems for therapeutic molecules is proposed. Many strategies have been recently developed to produce matrices with the desirable properties of molecular release, and enzymes could be playing a relevant role in modify the chemical composition of the polymers, the porosity and surface area of the matrices and modulate the kinetic of controlled release. Enzyme based computational systems have appeared as a relevant complementary tool to design novel smart bioactive matrices for programmable drug delivery. The present review is reporting the recent advances and projections of smart biopolymeric matrices activated by enzymes for sustained release of therapeutic molecules, highlighting various applications in the area of advanced drug delivery.

In situ Formed Implants, Based on PLGA and Eudragit Blends, for Novel Florfenicol Controlled Release Formulations.

Drug controlled release technologies (DCRTs) represent an opportunity for designing new therapies. Main objectives are dose number optimization and secondary effects reduction to improve the level of patient/client acceptance. The present work studies DCRTs based in blended polymeric implants for single dose and long-term therapies of florfenicol (FF), a broad spectrum antibiotic. Polymers used were PLGA and Eudragit E100/S100 types. Eudragit/PLGA and FF/PLGA ratios were the main studied factors in terms of encapsulation efficiencies (EEs) and drug release profiles. In addition, morphological and physicochemical characterization were carried out. EEs were of 50-100% depending on formulation composition, and the FF releasing rate was increased or diminished when E100 or S100 were added, respectively. PLGA hydrolytic cleavage products possibly affect Eudragit solubility and matrix stability. Different mathematical models were used for better understanding and simulating release processes. Implants maintained the antimicrobial activity against Pseudomonas aeruginosa up to 12 days on agar plates. The developed DCRTs represents a suitable alternative for florfenicol long-term therapies.

Design of nalidixic acid­vanadium complex loaded into chitosan hybrid nanoparticles as smart strategy to inhibit bacterial growth and quorum sensing.

The discovery of new alternatives for the treatment of infectious diseases has become the focus of burgeoning global interest. The complexation of the wide-spectrum antibiotic nalidixic acid (NA) with oxidovanadium(IV) ion and its incorporation into hybrid nanoparticulate systems were explored. The V-NA complex proved to be a stronger antimicrobial agent against E. coli, B. cereus, S. aureus and P. aeruginosa than NA, based on inhibition experiments. Myristyl myristate nanostructured lipid carriers (NLCs) and polymeric nanoparticles of Eudragit NE30D (EuNPs) were hybridized with chitosan (chi) to increase their stability and mucoadhesivity. They showed V-NA encapsulation of 97.8 ± 0.5% and 96.1 ± 0.1% respectively. TEM and DLS characterization ascertained the presence of spherical positive charged NPs ranging from 170 to 330 nm. Controlled release of V-NA from NPs was observed with 30-40% release in 3 days. A considerable potentiation of V-NA antimicrobial activity from 5 to 10 times was elucidated against P. aeruginosa with MIC values of 59.3 and 129.9 µM for NLC/chi and EuNPs/chi respectively, in comparison with 625 µM of the free complex. Hybrid NPs were able to interfere with the quorum sensing of the reporter Chromobacterium violaceum. Cytotoxicity on mouse fibroblast L929 cells was evaluated in the range of 29.7-519 µM by MTT assay showing that, NLC/chi particles supported cell growth in the range of at 29.7-60 µM while Eu/chi do not exert cytotoxicity between 29.7 and 120 µM. These results suggest that nanoparticles are suitable systems for drug delivery applications.

Chitosan-bacterial cellulose patch of ciprofloxacin for wound dressing: Preparation and characterization studies.

Biopolymeric blends based on bacterial cellulose (BC) films modified with low molecular weight chitosan (Chi) were developed for controlled release of ciprofloxacin (Cip). Biophysical studies revealed a compatible and cooperative network between BC and Chi including deep structural changes in the BC matrix shown by spectroscopic and thermal analyses (SEM, roughness analysis, FTIR, XRD, TGA, mechanical properties and water vapor transmission rate). Incorporation of chitosan to BC matrix generated a thickening scaffold with high permeability to water vapor from 0.7 to 3.2 g mm/m2 h. Cip loaded onto the BC-Chi film showed a hyperbolic release profile with a 30% decrease in antibiotic release mediated by the presence of Chi. BC-Chi blend films containing Cip tested against Pseudomonas aeruginosa and Staphylococcus aureus showed a synergic effect of chitosan on Cip antimicrobial activity. Besides, in vitro studies revealed the lack of cytotoxicity of BC-Chi-Cip films in human fibroblasts.

Formation and characterization of self-assembled bovine serum albumin nanoparticles as chrysin delivery systems.

Chrysin (5,7-dihydroxyflavone) (Chrys) is a natural flavone extracted from many plants, and it has been proposed as a bioactive agent for cancer therapy. Nevertheless, its use is limited mainly due to its poor water solubility. Bovine serum albumin (BSA) is a water soluble, biocompatible and non-toxic protein with a promising application in lipophilic bioactive compound delivery. Moreover, BSA is heat sensitive, feature that could be used for producing self-assembled nanoparticle with tailor-made properties. In this contribution, we studied the formation of BSA nanoparticles (BSAnp) by thermal treatment at different conditions of temperature (70 °C/5 min and 85 °C/5 min), protein concentration (1.0-4.0%wt.) and aqueous medium pH values (9.0 and 11.0) in which it is known that BSA is found in different unfolded conformations. Binding of Chrys dissolved in dimethyl sulfoxide (DMSO) was studied by fluorescence titration experiments. Characterization of Chrys-loaded and unloaded BSAnp was performed in phosphate buffered saline (PBS) pH 7.4 by applying a set of complementary techniques: dynamic light scattering (DLS), size exclusion fast protein liquid chromatography (SEC-FPLC) and transmission electron microscopy (TEM). Different populations of BSAnp were obtained, which showed different diameters in the range of 1328 nm, ζ potentials around -10.0 mV, molecular weight in the range of 400-1000 kDa and spherical shape. Chrys encapsulation efficiency (EE. %) was also determined, and values between 44-84% were obtained, which mainly depended on the mode of Chrys binding and physicochemical BSAnp properties. Results highlight the ability of self-assembled BSAnp for Chrys vehiculization in an aqueous medium which could found potential application in antitumor therapies.

Simple colorimetric method to determine the in vitro antioxidant activity of different monoterpenes.

The development of simple, fast and reproducible techniques that provide information about the antioxidant activity (AA) of different compounds is essential to screen and discover new molecules with potential applications in the therapeutic, cosmetic, toxicological and food fields. Here, a novel and simple colorimetric method ("BCB assay") is proposed for measuring the AA of chemical compounds by protection of the reporter dye Brilliant Cresyl Blue (BCB) from loss of color due to oxidation by hypochlorite (a physiological oxidant). The decay in BCB blue color (λmax = 634 nm) in the presence of hypochlorite occurred in only 5 min and was used to track the AA of different molecules. Particularly, the AA of monoterpenes was demonstrated and used to quantify them at milimolar concentrations. Natural antioxidants like vitamins C and E, resveratrol, dithiothreitol, N-actyl-l-cysteine and glutathione were used as controls to validate the assay. Linalool, geraniol and 1,8-cineole were tested and showed in vitro AA in a concentration-dependent manner. The monoterpene concentrations providing 50% protection against oxidation (AA50) were 2.3, 36.2 and 135.0 mM for linalool, geraniol and 1,8-cineole respectively, suggesting interesting AA. The method provides a useful, fast, simple and low-cost tool to determine the in vitro AA of different molecules.

Design, characterization and in vitro evaluation of linalool-loaded solid lipid nanoparticles as potent tool in cancer therapy.

Linalool (LN) is a monoterpene found in essential oils of plants and herbs that produces multiple effects on the mevalonate pathway and interesting antiproliferative activity in cancer cells. However, due to its poor aqueous solubility, an efficient vehicle is needed to improve its administration and bioavailability in physiological media. LN encapsulation in solid lipid nanoparticles (SLN) with different compositions was explored and in vitro tested in two cancer cell lines. SLN of myristyl myristate (MM), cetyl esters (SS) and cetyl palmitate (CP) were prepared by sonication in the presence of Pluronic®F68 as surfactant. Nanoparticle size, morphology and distribution were determined by dynamic light scattering in combination with optical and transmission electron microscopy (TEM). SLN showed spherical shape and mean diameters in the range of 90-130nm with narrow size dispersion (PDI values lower than 0.2) and Z potentials around -4.0mV. The encapsulation percentages of LN in SLN were higher than 80% for all tested formulations and exhibited in vitro LN controlled release profiles for at least 72h. The nanoparticles were physicochemically characterized by FTIR, XRD, DSC and TGA, and the incorporation of LN into SLN was higher than 80% in tested matrices. The developed formulations, and in particular SLN (MM)-LN, showed in vitro antiproliferative effects on hepatocarcinoma (HepG2) and lung adenocarcinoma (A549) cell lines in a dose-dependent response, and higher inhibitory effects were found in comparison with free LN. The cellular uptake of SLN was demonstrated by fluorescence microscopy, enhancing the ability of nanoparticles to intracellularly deliver the cargo molecules.

Nanopharmaceuticals as a solution to neglected diseases: Is it possible?

The study of neglected diseases has not received much attention, especially from public and private institutions over the last years, in terms of strong support for developing treatment for these diseases. Support in the form of substantial amounts of private and public investment is greatly needed in this area. Due to the lack of novel drugs for these diseases, nanobiotechnology has appeared as an important new breakthrough for the treatment of neglected diseases. Recently, very few reviews focusing on filiarasis, leishmaniasis, leprosy, malaria, onchocerciasis, schistosomiasis, trypanosomiasis, and tuberculosis, and dengue virus have been published. New developments in nanocarriers have made promising advances in the treatment of several kinds of diseases with less toxicity, high efficacy and improved bioavailability of drugs with extended release and fewer applications. This review deals with the current status of nanobiotechnology in the treatment of neglected diseases and highlights how it provides key tools for exploring new perspectives in the treatment of a wide range of diseases.

Kefiran-alginate gel microspheres for oral delivery of ciprofloxacin.

Ciprofloxacin is a broad-spectrum antibiotic associated with gastric and intestinal side effects after extended oral administration. Alginate is a biopolymer commonly employed in gel synthesis by ionotropic gelation, but unstable in the presence of biological metal-chelating compounds and/or under dried conditions. Kefiran is a microbial biopolymer able to form gels with the advantage of displaying antimicrobial activity. In the present study, kefiran-alginate gel microspheres were developed to encapsulate ciprofloxacin for antimicrobial controlled release and enhanced bactericidal effect against common pathogens. Scanning electron microscopy (SEM) analysis of the hybrid gel microspheres showed a spherical structure with a smoother surface compared to alginate gel matrices. In vitro release of ciprofloxacin from kefiran-alginate microspheres was less than 3.0% and 5.0% at pH 1.2 (stomach), and 5.0% and 25.0% at pH 7.4 (intestine) in 3 and 21h, respectively. Fourier transform infrared spectroscopy (FTIR) of ciprofloxacin-kefiran showed the displacement of typical bands of ciprofloxacin and kefiran, suggesting a cooperative interaction by hydrogen bridges between both molecules. Additionally, the thermal analysis of ciprofloxacin-kefiran showed a protective effect of the biopolymer against ciprofloxacin degradation at high temperatures. Finally, antimicrobial assays of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhymurium, and Staphylococcus aureus demonstrated the synergic effect between ciprofloxacin and kefiran against the tested microorganisms.

Smart lipid nanoparticles containing levofloxacin and DNase for lung delivery. Design and characterization.

Levofloxacin (LV) is a hydrophilic broad-spectrum antibiotic commonly used in pulmonary treatment against recurrent infections of Pseudomonas aeruginosa, and particularly in cystic fibrosis (CF) disease. In order to study feasible carriers for LV, solid lipid nanoparticles (SLN) of myristyl myristate were prepared by the ultrasonication method in the presence of Pluronic(®)F68 under different experimental conditions and characterized by dynamic light scattering, optical, transmission and scanning electron microscopy for size and morphology. Alternatively, nanostructured lipid carriers (NLCs) were developed to improve LV encapsulation and storage. SLN showed 20.1±1.4% LV encapsulation efficiency, while the NLCs encapsulated 55.9±1.6% LV. NLC formulation exhibited a more controlled release profile than SLN formulation, but both showed a biphasic drug release pattern with burst release at the first 5h and prolonged release afterwards, demonstrated by in vitro tests. The hydrodynamic average diameter and zeta potential of NLC were 182.6±3.2nm and -10.2±0.2mV, respectively, and were stable for at least 3 months. Additionally, DNase type I was incorporated into the formulations as a "smart" component, since the enzyme could help to decrease the viscoelasticity found in the lungs of CF patients and improves the antibiotic diffusion. FTIR, XRD, DSC, TGA and nitrogen adsorption isotherms of the nanoparticles indicate the presence of the loads in a noncrystalline state. The developed formulation showed an active antimicrobial activity against P. aeruginosa and even against other opportunistic pathogens such as Staphylococcus aureus. The presence of LV-loaded NLCs reduced the formation of a bacterial biofilm, which highlighted the significance of the nanodevice as a new alternative for CF treatment.

Nanodevices for the immobilization of therapeutic enzymes.

Therapeutic enzymes are one of the most promising applications of this century in the field of pharmaceutics. Biocatalyst properties can be improved by enzyme immobilization on nano-objects, thereby increasing stability and reusability and also enhancing the targeting to specific tissues and cells. Therapeutic biocatalyst-nanodevice complexes will provide new tools for the diagnosis and treatment of old and newly emerging pathologies. Among the advantages of this approach are the wide span and diverse range of possible materials and biocatalysts that promise to make the matrix-enzyme combination a unique modality for therapeutic delivery. This review focuses on the most significant techniques and nanomaterials used for enzyme immobilization such as metallic superparamagnetic, silica, and polymeric and single-enzyme nanoparticles. Finally, a review of the application of these nanodevices to different pathologies and modes of administration is presented. In short, since therapeutic enzymes constitute a highly promising alternative for treating a variety of pathologies more effectively, this review is aimed at providing the comprehensive summary needed to understand and improve this burgeoning area.

Characterization of smart auto-degradative hydrogel matrix containing alginate lyase to enhance levofloxacin delivery against bacterial biofilms.

The aim of the present work is the characterization of smart auto-degradable microspheres composed of calcium alginate/high methoxylated pectin containing an alginate lyase (AL) from Sphingobacterium multivorum and levofloxacin. Microspheres were prepared by ionotropic gelation containing AL in its inactive form at pH 4.0. Incubation of microspheres in Tris-HCl and PBS buffers at pH 7.40 allowed to establish the effect of ion-chelating phosphate on matrix erodability and suggested an intrinsically activation of AL by turning the pH close to neutrality. Scanning electron and optical microscopies revealed the presence of holes and surface changes in AL containing microspheres. Furthermore, texturometric parameters, DSC profiles and swelling properties were showing strong changes in microspheres properties. Encapsulation of levofloxacin into microspheres containing AL showed 70% efficiency and 35% enhancement of antimicrobial activity against Pseudomonas aeruginosa biofilm. Levofloxacin release from microspheres was not changed at acidic pH, but was modified at neutral pH in presence of AL. Advantageously, only gel matrix debris were detectable after overnight incubation, indicating an autodegradative gel process activated by the pH. Absence of matrix cytotoxicity and a reduction of the levofloxacin toxicity after encapsulation were observed in mammalian CHO-K1 cell cultures. These properties make the system a potent and versatile tool for antibiotic oral delivery targeted to intestine, enhancing the drug bioavailability to eradicate bacterial biofilm and avoiding possible intestinal obstructions.

Development of biopolymer nanocomposite for silver nanoparticles and Ciprofloxacin controlled release.

Screening of biopolymeric gel beads containing Silver NanoParticles (Ag-NPs) stabilized in Guar Gum Alkyl Amine (GGAA) and Ciprofloxacin (Cip) was carried out in order to obtain a novel nanocomposite with controlled release profile of both antimicrobians. The selected matrix composed of Alginate/High Methoxyl Pectin (HMP)/GGAA (4:4:1) was able to co-incorporate Ag-NPs and Cip with encapsulation efficiency higher than 70%. SEM images revealed good cohesivity and compatibility between the biopolymers and the cargos. Beads provided protection against Ag-NPs degradation at acidic pHs and HMP would played a key role providing hydrophobic regions. While Cip release profile showed a pH independent diffusional process, Ag-NPs release was restricted to matrix erodability. Calcium quelating agents and/or alginate degrading enzymes could modulate the release profile. The bactericidal activity of beads was tested in liquid medium, showing cooperative effects between the antimicrobials against Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus and Staphylococcus aureus. TEM images confirmed interaction of Ag-NPs with bacterial surfaces followed by membrane damage. Results suggested the nanocomposite matrix as a promising system for oral treatment of intestinal infectious diseases caused by multidrug resistant and unknown microorganisms, since both Cip and Ag-NPs would be able to reach intestine in the active form.

Characterization and stability analysis of biopolymeric matrices designed for phage-controlled release.

Alginate and low methoxylated pectin gel matrices emulsified with oleic acid were studied for phage oral delivery. Matrix structural analysis revealed that emulsified pectin (EP) gel microbeads were harder and more cohesive than those of emulsified alginate (EA). EP showed high swelling capacity and slower matrix degradation in aqueous media, suggesting that oleic acid is mainly located on the surface of EP microbeads. EA and EP matrices having p-nitrophenyl palmitate (C-16 ester) as tracer dissolved into oleic acid and in the presence of lipase confirmed this hypothesis which is consistent with EP better phage protective capability. Surface analysis of gel microbeads by scanning electron microscopy revealed strong differences between EP and EA gel microbeads. Phage release kinetics was tested using semi-empirical mathematical models. Experimental curve best fitted the Korsmeyer-Peppas model, predicting transport mechanisms according to the high swelling and degradation of EP. The proposed encapsulation model represents an innovative technology for phage therapy, which can be extrapolated to other therapeutic purposes, using a simple environmentally friendly synthesis procedure and cheap food-grade raw materials.

Tailoring of alginate-gelatin microspheres properties for oral Ciprofloxacin-controlled release against Pseudomonas aeruginosa.

CONTEXT: Ciprofloxacin (Cip) is a broad spectrum antibiotic frequently used in the treatment of infectious diseases caused by Pseudomonas aeruginosa. Cip oral administration is commonly associated with poor drug biodisponibility, gastrointestinal tract irritation, and toxic undesirable side effects. OBJECTIVE: The aim of this work is to provide an oral biopolymeric system for controlled release of Cip. MATERIALS AND METHODS: Alginate-gelatin blend microspheres were crosslinked in the presence of 1,2-propylene glycol, calcium, and glutaraldehyde. Studies of Cip encapsulation and release were performed. Matrix characteristics were studied simultaneously by optical microscopy and Fourier transform infrared spectroscopy (FTIR) using synchrotron light, and by texturometric analysis. Microsphere surface topologies were observed by scanning electron microscopy (SEM), atomic force microscopy (AFM), and epifluorescence microscopy. RESULTS: Microspheres crosslinked with glutaraldehyde showed about 80% Cip encapsulation and less than 10% Cip release under simulated gastric conditions in 15 min, while a controlled release profile was observed at intestinal environment conditions. Antimicrobial activity against P. aeruginosa showed an increasing bacterial growth inhibition in time. Finally, bovine serum albumin (BSA) was used as model protein for binding of macromolecules onto active surface of microspheres, with a consequently modulation of Cip release. DISCUSSION AND CONCLUSIONS: The results are indicating that alginate/gelatin matrix crosslinked via Ca(2+) and glutaraldehyde can be tailored by decorating the microsphere surface with biological active molecules useful for targeting, making a potential tool to improve Cip oral administration for infection diseases.

Alginate lyase and ciprofloxacin co-immobilization on biopolymeric microspheres for cystic fibrosis treatment.

A new formulation is described based on biopolymeric microspheres containing alginate lyase (AL) and ciprofloxacin (Cip) for sustainable oral delivery in CF patients. Alginate (ALG) and high-methoxyl pectin (HMP) are selected as the biopolymers to develop a composite matrix. ALG microspheres coated with HMP and ALG-HMP blend are gelled in water/organic solvents mixtures, obtaining Cip encapsulations from 46.0 to 100.0%. ALG-HMP shows a Cip sustainable release profile and is able to encapsulate 90.0% of AL, showing 76.0% enzyme activity after release under simulated intestinal conditions. The developed system is a promising delivery carrier to treat chronic infection of Pseudomonas aeruginosa and to reduce the viscoelasticity of the mucus accumulated into intestine of CF patients.