Controlled Release of Sulfasalazine Release from “Smart” Pectin Gel Microspheres under Physiological Simulated Fluids

Sulfasalazine (SLZ) is a synthetic nonsteroidal anti-inflammatory drug used mainly for the treatment of an inflammatory bowel and other diseases. Two pectins with different methylation degrees were blended to synthesized gel microspheres by ionotropic gelation for SLZ encapsulation. The encapsulation efficiency was found to be around of 99% in all formulations tested. However, different SLZ release profiles related to the methylation degrees of pectin were observed. Mixture of low methylated (LM) and high methylated (HM) pectins in the presence of calcium(II) displayed the best microsphere morphologies among the formulations tested determined by optical and electronic microscopies. The percentage of drug release using a mixture of LM and HM pectins after 255?min in simulated gastric fluid (pH?=?1.2), simulated intestinal fluid (pH?=?6.8), and phosphate buffer (pH?=?7.4) were 15.0%, 47.0%, and 52.2%, respectively.     

Studies of Ciprofloxacin Encapsulation on Alginate/Pectin Matrixes and Its Relationship with Biodisponibility

Screening of ciprofloxacin (Cip) with selected biopolymers brings about 90% antibiotic interactions with a coacervate composed of alginate/high metoxylated pectin in 2:1 ratio. Fourier transform infrared spectroscopy analysis provides information about the nature of this interaction, revealing ionic and hydrophobic patterns among the molecules. Alginate/high methoxylated pectin gel microspheres developed by ionic gelation encapsulates 46.8?±?5.0% Cip. The gel matrix can release Cip in a sustained manner, releasing 42.7?±?0.2% in 2?h under simulated stomach pH conditions, and 83.3?±?1.1% Cip release in 80?mM phosphate at pH?=?7.40 (intestinal). The increase of sodium chloride from 50 to 200?mM implies a Cip release from 69.0?±?1.5% to 95.1?±?3.6% respectively in 2?h. Scanning electron microscopy revealed the cohesive effect of HM pectin over alginate molecules on the microsphere surface. Those results guarantee all Cip contained in the alginate/HM pectin microspheres could be released in an established kinetic profile along the gastrointestinal tract, avoiding the Cip undesirable side effects during absorption.     

Effect of Molecular Weight on Packing during Latex Film Formation

A UV-visible technique is used to study the evolution of transparency during film formation from latex particles. Latex particles with high and low molecular weight (HM and LM) polymethyl methacrylate (PMMA) are used to prepare films. Two sets of films with different latex content were prepared from HM and LM particles separately, by annealing PMMA particles above the glass transition temperature. Transmitted photon intensity, I(tr), from HM and LM films increased as the annealing temperature was increased. The increase in the transmitted photon intensity is attributed to the latex content (film thickness) for the annealed film samples. It is suggested that as the latex particles are packed (film thickness is increased) fewer voids or cracks are formed in the films. Positive and negative absorption coefficients are measured below and above 210 and 180 degrees C annealing temperatures for the HM and LM films. Packing coefficients are obtained for films in various latex contents. It is observed that LM particles are packed much easier than HM particles. Copyright 2001 Academic Press.     

Characterization of Food Packaging Films with Blackcurrant Fruit Waste as a Source of Antioxidant and Color Sensing Intelligent Material

Chitosan and pectin films were enriched with blackcurrant pomace powder (10 and 20% (w/w)), as bio-based material, to minimize food production losses and to increase the functional properties of produced films aimed at food coatings and wrappers. Water vapor permeability of active films increased up to 25%, moisture content for 27% in pectin-based ones, but water solubility was not significantly modified. Mechanical properties (tensile strength, elongation at break and Young’s modulus) were mainly decreased due to the residual insoluble particles present in blackcurrant waste. FTIR analysis showed no significant changes between the film samples. The degradation temperatures, determined by DSC, were reduced by 18 °C for chitosan-based samples and of 32 °C lower for the pectin-based samples with blackcurrant powder, indicating a disturbance in polymer stability. The antioxidant activity of active films was increased up to 30-fold. Lightness and redness of dry films significantly changed depending on the polymer type. Significant color changes, especially in chitosan film formulations, were observed after exposure to different pH buffers. This effect is further explored in formulations that were used as color change indicators for intelligent biopackaging.     

Molecular Weight Effect on Latex Film Formation from Polystyrene Particles: A Photon Transmission Study

The photon transmission method was used to probe the time evolution of film formation from latex particles. Two different latex films were prepared from high molecular weight (HM) and low molecular weight (LM) polystyrene particles at room temperature and were annealed at various temperatures in 2.5-min time intervals above the glass transition. The increase in the transmitted photon intensity (Itr) is attributed to the increase in "crossing density" at the junction surface. The Prager-Tirrell model was employed to interpret the increase in crossing density at the junction surface. The back and forth activation energies were measured for HM and LM films and found to be around 59 and 87 kcal/mol for a reptating polymer chain across the junction surface. Monte Carlo simulations were performed for photon transmission through a rectangular lattice. The number of transmitted photons (Ntr) was calculated as a function of the mean free path of photons. It was observed that Ntr, similar to Itr, increases as the square of the mean free path of photons is increased. Copyright 1999 Academic Press.     

Polyvinyl Alcohol–Pectin Cryogel Films for Controlled Release of Enrofloxacin

The release of enrofloxacin entrapped in polyvinyl alcohol (PVA) cryogel at pH?5.5 showed a first-order kinetic, releasing 69.7% of the antibiotic after 4.5?h at 37?°C. In order to slow down the fluoroquinolone release rate, high-methoxylated pectin was added into the cryogel (PVA?CP). A film containing 1.0% (w/v) HM pectin and 5.0???g/ml enrofloxacin released only 3.7% of the antibiotic after 4.5?h. Since the FTIR spectrum showed that most of the interactions between PVA?CP matrix and enrofloxacin were due to polar groups (carboxylate and amine), a two-layer film system was designed to modulate the releasing rate of the drug. The top film equilibrated with 0.75 or 1.5?M NaCl release up to 41.9% and 89.0% of the enrofloxacin in 4?h, respectively. The release rate of enrofloxacin was found dependent on NaCl concentration in the upper gel layer. The two-layer cryogel system showed attractive features for transcutaneous antibiotic delivery.     

A photon transmission study for film formation from poly(vinyl acetate) latex particles with different molecular weights

The photon transmission technique was used to monitor the temperature evolution of film formation from poly(vinyl acetate) (PVAc) latex particles with two different molecular weights. Two sets of latex films were prepared below the glass transition temperature (T_g) of PVAc, which are named as low (LM) and high molecular weight (HM) films. These films were annealed at elevated temperatures above the T_g of PVAc for various time intervals. It is observed that transmitted photon intensity (I_tr) from these films increased as the annealing temperature was increased. Onset temperatures (T_H) at given times (τ_H) for starting the optical clarity of LM and HM films were measured and used to calculate the healing activation energies (ΔH) for the PVAc minor chains, and found to be as 28.1 kcal/mol and 27.7 kcal/mol, respectively. The increase in the transmitted photon intensity, I_tr above T_H was attributed to the increase in the number of disappeared interfaces between the deformed latex particles. Prager–Tirrell (PT) model was employed to interpret the increase in the crossing density of chains at the junction surfaces. The interdiffusion (backbone) activation energies (ΔE) were measured and found to be 177.5 kcal/mol and 210.7 kcal/mol for a diffusing PVAc chains across the junction surface of LM and HM latex films, respectively. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 2918–2925, 2007     

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.     

Alginate/gelatin blend films and their properties for drug controlled release

Films of alginate and gelatin, cross-linked with Ca²⁺, with ciprofloxacin hydrochloride as model drug incorporated in different concentrations, were obtained by a casting/solvent evaporation method. Chemical, morphological and mechanical properties characterization was carried out, as well as the studies of the factors that influence the drug releasing from alginate and gelatin films. These factors included the component ratio of alginate and gelatin, the loaded amount of ciprofloxacin hydrochloride, the pH and ionic strength of the release solution, the thickness of the drug loaded films and the cross-linking time with Ca²⁺ and others. The best values of the tensile strength at 101.5 MPa and breaking elongation at 19.4% of blend films were obtained when the gelatin content was 50 wt.%. The results of controlled release tests showed that the amount of ciprofloxacin hydrochloride released decreased with an increase in the proportion of gelatin present in the film. Moreover, the release rate of drug decreased as the amount of drug loaded in the film increased. The alginate/gelatin films were also sensitive to pH and ionic strength. For pH 7.4 the drug release was faster compared to pH 3.6, being simultaneously accelerated by a higher ionic strength. It was observed that in simulated intestinal fluid, the thickness of the film increased from 30 μm to 55 μm with a concomitant reduction of the ciprofloxacin hydrochloride concentration from 100% to 83.5%. When the cross-linking time of these films in the Ca²⁺ solution were 0 min, 5 min, 15 min and 30 min, the drug release rate attained 100%, 100%, 77.6% and 52.4%, respectively, within 24 h. All the results indicated that the alginate/gelatin film was potentially useful in drug delivery systems.     

Kappa-Carrageenan/PVA Filmswith Antibacterial Properties: Part 1. Optimization of Preparation Conditions and Preliminary Drug Release Studies

In this work, kappa carrageenan (KC) and poly(vinyl alcohol) are crosslinked with glutaraldehyde (GTA) to produce films without using catalyst HCL. The optimum conditions for the formation of film have been established based on their water absorption property. The crosslinking reaction was confirmed by FTIR analysis.The films were also characterized by scanning electron microscopy(SEM) and X-ray diffraction (XRD) analysis.The equilibrium swelling of films showed fair dependency on the presence of salt in the swelling medium.However, pH dependent swelling behavior was not prominent. Finally, a representative film sample was loaded with antibacterial drug Gentamicin sulphate and release was monitored kinetically in the physiological fluid (PF) at 37°C. The film showed fair antibacterial action against model bacteria E.Coli.     

Complexation of Anthocyanin-Bound Blackcurrant Pectin and Whey Protein: Effect of pH and Heat Treatment

A complexation study between blackcurrant pectin (BCP) and whey protein (WP) was carried out to investigate the impact of bound anthocyanins on pectin–protein interactions. The effects of pH (3.5 and 4.5), heating (85 °C, 15 min), and heating sequence (mixed-heated or heated-mixed) were studied. The pH influenced the color, turbidity, particle size, and zeta-potential of the mixtures, but its impact was mainly significant when heating was introduced. Heating increased the amount of BCP in the complexes—especially at pH 3.5, where 88% w/w of the initial pectin was found in the sedimented (insoluble) fraction. Based on phase-separation measurements, the mixed-heated system at pH 4.5 displayed greater stability than at pH 3.5. Heating sequence was essential in preventing destabilization of the systems; mixing of components before heating produced a more stable system with small complexes (<300 nm) and relatively low polydispersity. However, heating WP before mixing with BCP prompted protein aggregation—producing large complexes (>400 nm) and worsening the destabilization. Peak shifts and emergence (800–1200 cm⁻¹) in infrared spectra confirmed that BCP and WP functional groups were altered after mixing and heating via electrostatic, hydrophobic, and hydrogen bonding interactions. This study demonstrated that appropriate processing conditions can positively impact anthocyanin-bound pectin–protein interactions.     

Functional properties of “cotton protein.” III. Influence of gossypol and phytates on the solubility of gossypulin

The solubility of gossypulin and its derivatives under various conditions has been studied by turbidimetric titration. It was found that the low solubility of the protein under investigation in the neutral range of pH values at a low ionic strength may be due to the presence of phytin and gossypol. The minimum in the solubility of the gossypol-free protein shifted into the more alkaline region (pH 6.0–6.7) as compared with the initial gossypulin (with 0.6% of gossypol). The treatment of gossypulin with dilute solutions of phytin at pH 5.0 led to a shift in the pH of precipitation (pH 3.75), but in the presence of an excess of phytic acid the aggregation capacity of the protein increased and the pH of precipitation changed (pH 4.5–5.0). When Ca²⁺ ions were added, there was a shift of the solubility minimum into the alkaline pH range. In the presence of pectin, the pH of precipitation of all the samples studied shifted into a more acid pH range.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 359–364, May–June, 1986.     

Stimuli‐responsive micelles of amphiphilic AMPS‐b‐AAL copolymers in layer‐by‐layer films

Aqueous reversible addition‐fragmentation chain transfer polymerization was used to synthesize poly(N‐[3‐(dimethylamino)propyl]acrylamide) (PDMAPA) cationic homopolymers and micelle‐forming, pH‐responsive, amphiphilic diblock copolymers of poly(sodium 2‐acrylamido‐2‐methyl‐1‐propanesulfonate‐block‐N‐acryloyl‐L ‐alanine) (P(AMPS‐b‐AAL)). At low pH, the AAL blocks are protonated rendering them hydrophobic, whereas the AMPS blocks remain anionically charged because of the pendant sulfonate groups. Self‐assembly results in core–shell micelles consisting of hydrophobic cores of AAL and negatively charged shells of AMPS. Using solutions of these micelles with anionic coronas and of the cationic homopolymer PDMAPA, layer‐by‐layer (LbL) films were assembled at low pH, maintaining the micelle structures. Several block copolymers with varying AMPS and AAL block lengths were synthesized and used in the formation of LbL films. The thickness and morphology of the films were examined using ellipsometry and atomic force microscopy. The stimuli‐responsive behavior can be triggered by submersion of the film in water at neutral pH to disrupt the micelles. This behavior was monitored by observing the decrease in film thickness and alteration of the film morphology. The micelles were also loaded with a model hydrophobic compound, pyrene, and incorporated into LbL films. The release of pyrene from the films was monitored by fluorescence spectroscopy at varying pH values (1, 3, 5, and 7). As the pH of the solution increases, the rate of release increases. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Studies on pectin coating of liposomes for drug delivery

The present study investigated the surface coating of charged liposomes by three different types of pectin (LM, HM and amidated pectin) by particle size determinations and zeta potential measurements. The pectins and the pectin coated liposomes were visualized by atomic force microscopy. The adsorption of pectin onto positive liposomes yielded a reproducible increase in particle size and a shift of the zeta potential from positive to negative side for all three pectin types, whereas the adsorption of pectin onto negative liposomes did not render any significant changes probably due to electrostatic repulsion. The positive liposomes coated with HM-pectin gave the largest pectin coated particles with the least negative zeta potential, while the opposite was observed for the LM-pectin coated positive liposomes. Furthermore, results from dynamic light scattering revealed narrow size distributions, indicating that the degree of aggregation was low for the pectin coated liposomes. As liposomes are able to encapsulate drugs and pectin has been found to be mucoadhesive, these pectin coated liposomes may be potential drug delivery systems.     

Facile tailoring of film morphology and release properties using layer-by-layer assembly of thermoresponsive materials

Layer-by-layer self-assembly was used to prepare thermoresponsive thin films of poly(N-isopropylacrylamide) (PNIPAAm) and poly(acrylic acid) (PAA) based on hydrogen bonding. The temperature of PNIPAAm adsorption was shown to significantly affect both the mass proportion of PNIPAAm in the film and the film surface morphology. When the adsorption was conducted at temperatures close to the lower critical solubility temperature of PNIPAAm, the amount of PNIPAAm in the film increased significantly (from 51 to 59%), and the total film mass increased by 30-40%. The films prepared at 30 degrees C also exhibited a lower surface roughness (1-2 nm) compared with 5-8 nm when prepared at 10 or 21 degrees C. The resulting multilayer films ([PAA/PNIPAAm]10) were capable of being reversibly loaded and unloaded with dye (Rhodamine B) by exposure to solutions at elevated temperatures. The rate of loading and release was shown to depend on both the solution temperature and film preparation temperature, leading to tunable loading/release properties.     

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH-sensitive drug release property

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200 μm were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic complexation by alginate and/or pectin, as well as ionotropic gelation with calcium ions, the microparticles exhibited an improved pH-sensitive drug release property. The in vitro drug release behaviors of the microparticles were studied in simulated gastric (pH 1.2 and pH 5.0), intestinal (pH 7.4) and colonic (pH 6.0 and pH 6.8 with enzyme) media. For the composite microparticles with suitable compositions, the releases of BSA at pH 1.2 and pH 5.0 could be effectively sustained, while the releases at pH 7.4, pH 6.8 and pH 6.0 increased significantly, especially in the presence of pectinase. These results clearly suggested that the microparticles had potential for site-specific protein drug delivery through oral administration.     

PEO–PPO based star-block copolymer T904 as pH responsive nanocarriers for quercetin: Solubilization and release study

Solubilization of quercetin (QN), a hypolipidemic drug in aqueous micellar solution of a star-like octablock Tetronic® T904 covering different salt concentration, pH and temperature is investigated. The change in pH modulates the charge of the copolymer which alters the dibasic nature of the centrally located ethylenediamine moiety and makes T904 undergo deprotonation favoring self assembly. At low pH, the columbic repulsion among the positively charged amine groups of Tetronic® hinders micellization while presence of salt facilitates it. The drug solubility data for micelles in aqueous/salt solutions determined by UV–Visible spectroscopy and micellar size with loaded drug from dynamic light scattering (DLS) are reported. Hydrophobic/anionic QN, deprotonates T904 and induces the micellization in acidic pH thus assisting solubilization. The expected locus (site) of the QN in T904 micelles was successfully correlated by the significant and positive cross peaks obtained from two-dimensional nuclear Overhauser effect spectroscopy (2D-NOESY). The evaluated in vitro release profile employing different kinetic models explains the controlled release of drug from T904 micelles.     

Evaluation of Adding Natural Gum to Pectin Extracted from Ecuadorian Citrus Peels as an Eco-Friendly Corrosion Inhibitor for Carbon Steel

The production and use of eco-friendly corrosion inhibitors allows valuable compounds contained in plant waste to be identified and repurposed while reducing the use of polluting synthetic substances. Pectin extracted from Tahiti limes (Citrus latifolia) and King mandarin (Citrus nobilis L.) in addition to natural gums—xanthan gum and latex from the “lechero” plant (Euphorbia laurifolia)—were used to create an eco-friendly corrosion inhibitor. The optimal extraction conditions for pectin were determined from different combinations of pH, temperature, and time in a 2³ factorial design and evaluated according to the obtained pectin yield. The highest pectin extraction yields (38.10% and 41.20% from King mandarin and lime, respectively) were reached at pH = 1, 85 °C, and 2 h. Extraction of pectic compounds was confirmed using Fourier-transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetry analyses. Subsequently, a simplex-centroid mixture design was applied to determine the formulation of extracted pectin and natural gums that achieved the highest corrosion inhibitor effect (linear polarization and weight loss methods in NACE 1D-196 saline media using API-5LX52 carbon steel). Impedance spectroscopy analysis showed that the addition of xanthan gum to pectin (formulation 50% pectin–50% xanthan gum) improved the corrosion inhibitor effect from 29.20 to 78.21% at 400 ppm due to higher adsorption of inhibitory molecules on the metal surface.     

Reversible loading and unloading of nanoparticles in "exponentially" growing polyelectrolyte LBL films

The exponentially growing layer-by-layer (LBL) films made from poly(diallyldimethylammonium chloride) (PDDA) and poly(acrylic acid) (PAA) were used to load and unload the CdTe nanoparticles (NPs). The reversible loading of NPs were investigated through UV-vis studies and further confirmed by confocal microscopy. In addition the LBL films were also compared for the release kinetics for pH 9 and 7 and films capped with (PDDA-PSS)10 layers. The amount of released particles at pH 9 was found to be at least 2 orders of magnitude higher than those at pH 7 and with (PDDA-PSS)10 capped layers after 25 h. This variation in film response for CdTe-particle release presents a route for studies in which highly swollen exponentially growing LBL films can be loaded with functionalized NPs for biological applications and explored as carriers to hold the NPs inside the films for self-assembly.     

The role of polymer/drug interactions on the sustained release from poly(dl-lactic acid) tablets

The release profiles of model drugs (propranolol HCl, diclofenac sodium, salicylic acid and sulfasalazine) from low molecular weight poly(d,l-lactic acid) [d,l-PLA] tablets immersed in buffer solutions were investigated in an attempt to explore the mechanism of the related phenomena. It was confirmed that drug release is controlled by diffusion through the polymer matrix and by the erosion of the polymer. The pH of the surrounding medium influences the drug solubility as well as swelling and degradation rate of the polymer and therefore the overall drug release process. Physicochemical interaction between d,l-PLA and drug is an additional factor which influences the degree of matrix swelling and therefore its porosity and diffusion release process. Propranolol HCl shows extended delivery time at both examined pH values (5.4 and 7.4) and especially at pH 7.4 where release was accomplished in 190 days, most probably due to its decreased solubility at higher pH values. The acidic drugs gave shorter delivery times especially at pH 7.4. A slower drug release rate and more extended delivery time at pH 7.4 in comparison with that at pH 5.4 was recorded for tablets loaded with diclofenac sodium and salicylic acid. The opposite effect was observed with samples loaded with propranolol HCl.