Controlled Release Studies Research Articles

Camptothecin encapsulated into functionalized MCM-41: In vitro release study, cytotoxicity and kinetics

The application of MCM-41 functionalized by 12-tungstophosphoric acid (TPA) as drug carrier for cancer treatment was studied by loading of camptothecin (CPT). In-vitro controlled release study of CPT in Simulated Body Fluid (pH 7.4, 37 °C) was carried out under stirring as well as static conditions. The systems were also evaluated on cancer cells (HepG2) and the carriers are found to be non-toxic to the cancer cells. In order to see the influence of inorganic moiety on release rate of drug, study was also carried out with CPT loaded unfunctionalized MCM-41. A detailed study on release kinetics and release mechanism using First Order Release Kinetic Model, Higuchi Model, Koresmeyer-Pepps Model and Extended kinetic model was also carried out.

RETRACTED: Production, characterization and controlled release studies of biodegradable polymer microcapsules incorporating neem seed oil by spray drying

Abstract Azadirachtin is a biologically active constituent of neem seed oil, exhibiting medicinal and pesticidal properties. This work reports on the encapsulation of neem seed oil extract within three different polymeric shells: polyvinyl alcohol (PVA), gum arabic (GA) and whey protein isolate/maltodextrin (WPI/MD), using spray drying. The obtained, roughly spherical microcapsules had average sizes of 28.84 ± 11.86 μm, 32.43 ± 13.06 μm, and 52.88 ± 17.33 μm (obtained from PVA, GA, and WPI/MD, respectively). Fourier transform infrared spectroscopy confirmed the presence of the core and shell components, in addition to surface functional groups. Encapsulation efficiencies for neem seed oil proved higher in smaller microcapsules, although efficiency values of 60–92% were obtained in all cases. In vitro release of neem seed oil from the microcapsules followed the Ritger–Peppas model, as governed by Fickian diffusion. From these results, the association of botanical insecticides within biopolymer cores offer considerable potential for increasing agricultural production levels, and reducing impacts on the environment and human health.

Transglutaminase induced gels using bitter apricot kernel protein: Chemical, textural and release properties

Plant protein gels have a good biocompatibility and biodegradability to provide a non-reactive environment and control the release of sensitive or bioactive compounds. In this study, the effects of microbial transglutaminase (MTGase) catalyzed crosslinking on chemical interactions, textural properties and controlled release of gels made using bitter apricot kernel protein concentrate (APC) were investigated. As the MTGase concentration increased, the free amino and free sulfhydryl groups decreased, while the degree of crosslinking, disulfide bonding and surface hydrophobicity increased. A compact and homogenous network structure was observed using SEM. Textural profile analysis showed that MTGase induced crosslinking increased gel hardness, springiness and cohesiveness. In addition, in vitro controlled release studies showed that MTGase induced APC gels were able to resist acidic conditions and pepsin digestion, protected the riboflavin against simulated gastric fluid and allowed gradual release in simulated intestinal fluid. These APC gels may be suitable for delivering sensitive compounds into functional foods, as well as dietary supplements and pharmaceutical products.

Controlled release study of phenol formaldehyde based microcapsules containing various loading percentage of core cypermethrin at different agitation rates

Cypermethrin is a synthetic pyrethroid that acts as a neurotoxin and is used on large scale in both agricultural and domestic purposes. It is easily degraded on soil and plants but can be effective for weeks when applied to indoor inert surfaces. Sometimes it develops tingling, burning, dizziness, and itching to the operator which is why there is a need to develop a safe and effective formulation, which can release cypermethrin under controlled conditions. In this communication, we report a successful encapsulation of cypermethrin within shell of phenol formaldehyde (PF). A series of PF microcapsules have been prepared at various loading percentage and varying agitation rates by in situ polymerization. The formulation consists of mainly two parts, namely emulsification of the oil and wall formation. The morphology of formulated microcapsules was confirmed initially by observing under optical microscope and further with FESEM, which indicated spherical shape, smooth surface, and rigid nature to the microcapsules. The microcapsules were characterized by FTIR, TGA, and particle size analyzer. Release rate of cypermethrin from polymeric microcapsules was calculated by UV spectrophotometer and also by a simple gravimetric method. The stable, safe, and controlled release formulation of easily degradable, highly burning and etching cypermethrin is the success of our present work.

Microencapsulation of Curcumin by a Spray-Drying Technique Using Gum Arabic as Encapsulating Agent and Release Studies

Curcumin is a natural yellow pigment extracted from dried roots of turmeric, used in food applications. Despite its applicability in food products, this phenolic compound is also used in the pharmaceutical field. It is reported to have health benefits such as anticancer, antitumor, and antiviral effects. However, curcumin is a very unstable compound. Therefore, this work proposes the microencapsulation of curcumin, in order to protect it and to improve its stability and solubility in water, by spray-drying, using the gum arabic as an encapsulating agent in three different concentrations 10, 15, and 20% (weight/volume (w/v)). Emulsions were prepared with coconut oil and used to prepare the curcumin microparticles. For this purpose, different analysis and studies were performed. A product yield ranging from 44 to 52% and from 29 to 42% was obtained for the production of microparticles without and with curcumin, respectively. The curcumin microcapsules and empty capsules were characterized and evaluated. All the microparticles presented a spherical form, had a diameter around 7–9 μm (considering a volume distribution), and had a rough surface. The efficiency of encapsulation was between 75 and 85%, being higher for the particles prepared with higher concentrations of encapsulating agents. Considering the controlled release studies, the microcapsules were prepared with different concentrations of gum arabic but showed similar release profiles. However, it was also concluded that increasing the amount of gum arabic used in the formulation of the microparticles, the amount of curcumin released in the first minutes decreases; therefore, the release tends to be slower (63.2% of the release varied between 25.5 and 69.0 min). Fitting the experimental results to a linearized equation of the Weibull model, it was possible to obtain a good correlation coefficient (R2 varying from 0.94 to 0.97), indicating that this model adapts to the experimental data obtained.

Preparation of bergenin - Poly (lactic acid) polymers and in vitro controlled release studies

The efficacy of bergenin prepared with osmotic-pump-controlled release is much lower than expected. In this study, biodegradable polylactic acid is used to modify bergenin and immobilize it with chemical methods. Bergenin-PLA obtained by this method has low molecular weight and good thermal stability, as well as prolonged in vitro release time along with increased molecular weight. Biocompatibility tests and in vitro antitumor tests showed that bergenin-PLA at a ratio of 1:30 has good biological properties and low cytotoxicity at t three concentrations, and its antitumor activity was significantly increased compared to bergenin. The chemical immobilization of bergenin not only provides a good mode of administration for patients but also provides a good foundation for the sustained release of drugs over time.

Preparation of zinc layered hydroxide-ferulate and coated zinc layered hydroxide-ferulate nanocomposites for controlled release of ferulic acid

Ferulic acid (FA) was intercalated into zinc layered hydroxide (ZLH) to form a new nanocomposite, namely zinc layered hydroxide-ferulate (ZLH-FA) and was further coated by surfactants sodium dodecyl sulfate (SDS) and polysorbate 80 (Tween-80). XRD patterns of the ZLH-FA nanocomposite obtained reveals a crystalline structure with basal spacing of 26·9 Å. The XRD pattern of the coated nanocomposite showed similar peaks to the ZLH-FA nanocomposite. The loading of FA in the nanocomposite was estimated to be 56·82% (w/w), and its thermal stability was markedly enhanced compare to its free counterpart. A controlled release study showed that the FA was release was slower from interlayer of ZLH-FA/SDS and ZLH-FA/Tween-80 nanocomposites compared to the ZLH-FA nanocomposite. The mechanism of release follow the pseudo-second order kinetics model for all nanocomposites. Results from this study highlight the potential of these nanocomposites for controlled release formulation of FA drug anion.

Novel Thiolated Chitosan-Polyethyleneglycol blend/Montmorillonite composite formulations for the oral delivery of insulin

A novel drug delivery system is architectured at achieving systematically improved therapeutic success for drugs including those that have limited use because of toxicity, uneven distribution pattern, stability and formulation of difficulties. In the present work, we report on the preparation of a novel composite formulation, i.e., biodegradable Thiolated Chitosan- Polyethylene Glycol (TCS-PEG) blend incorporated with medical clay, MMT called TCS-PEG/MMT composites for the oral delivery of insulin. The different stages of the preparation were well characterized and the effects of pH on insulin loading along with controlled release studies were carried out. The drug release was monitored by changing time, % drug loading and pH of the medium. Results showed only 5% release of insulin after 2 h incubation in the simulating gastric condition and after 4 h incubation in the simulating intestinal conditions, the release profile enhanced to 67% at basic pH (7.4), which shows the release was much pronounced in the basic medium than in the acidic medium.

Thermocleavable friction modifiers for controlled release in lubricants

Abstract Organic friction modifiers (FMs) are commonly utilized in lubricants. FM molecules possess a polar head group that interacts with metallic surfaces and aliphatic chains that cohesively interact with neighboring molecules. Under boundary lubrication conditions, as experienced in engine valve trains and cylinders, fluid films are unable to form between metallic surfaces. This results in metal-metal contact. Thus, organic friction modifiers are commonly utilized to reduce friction under these conditions. While efficacious, these molecules are consumed over time owing to engine environments, reducing their effectiveness. To replenish organic friction modifier stocks in base oil lubricants, tertiary ester derivatives of fatty acid-containing dicarboxylic acids were investigated. A series of fatty acid-containing dicarboxylic acids were first developed based on a tartaric acid backbone and their friction modifying capabilities assessed. Coefficient of friction studies illustrated that friction-modifying capabilities were heavily influenced by polar head group type (i.e., carboxylic acid, ester) and chemical bond to tartaric acid (i.e., ester, ether). Thermogravimetric analysis coupled gas-phase Fourier transform infrared spectroscopy revealed that fatty acid-containing dicarboxylic acids degraded into their respective fatty acids at elevated temperatures. Controlled release studies were conducted on a compound modified with thermocleavable esters, and showed sustained friction modifying activity through the course of the entire study. These systems are ideal candidates for the controlled delivery of friction modifiers, which can increase engine efficiency and reduce fuel consumption, effectively reducing vehicle emissions.

Controlled release studies of boron and zinc from layered double hydroxides as the micronutrient hosts for agricultural application

Abstract Two forms of zinc-aluminium layered double hydroxides (ZnAl-LDH) with borate association (iZA and cZA) were prepared by ion-exchange process and in-situ co-precipitation. The received materials were examined using several characterization techniques, e.g. x-ray diffraction (XRD), scanning- and transmission-electron microscopy (SEM and TEM). The XRD diffractograms suggested that only monoborate ions (possibly trigonal and tetrahedral forms) were involved in the intercalation and adsorption. Elemental analyses, i.e. inductive coupled plasma-optical emission and atomic absorption spectroscopies, were used to determine the starting zinc and boron compositions, and the contents after the dissolution experiment in water, soil, and plant growth study. The iZA and cZA samples were found to controlled-release Zn and B contents which can be used as micronutrient sources in agricultural application. The releases of the two nutrients are suggested to initiate from the anionic-exchange of BO33 − and the transformation of Zn2 + from LDH basal plane. The plant experiments treated with these iZA and cZA exhibit improvements in plant growth, evidently attributed to the controlled and sustainable releases of boron and zinc for assisting macronutrient uptakes when used with the NPK fertilizer.

Synthesis, characterization and antibacterial activity of juglone encapsulated PLGA nanoparticles.

The aim of the study was to examine the effect of different process parameters which including; initial juglone amount, initial poly(d,l-lactide co-glycolide) amount, polyvinyl alcohol volume and polyvinyl alcohol concentration on encapsulation of juglone to poly(d,l-lactide co-glycolide) nanoparticles. The synthesized nanoparticle formulations were analyzed for reaction yield, encapsulation efficiency, particle size, polydispersity, zeta potential and juglone release. In conjunction with the highest encapsulation rate, the highest amount of juglone release was obtained for F4 formulation, which has 281·8nm particle size, 0·217 polydispersity index, and -19·55 mV zeta potential. After the detailed physicochemical characterization of this formulation, the four different kinetic models were used and it was found that juglone release mechanism controlled by Fickian diffusion method. According to antimicrobial activity results, minimal inhibitory concentration (MIC) values of both F4 and free juglone is higher for Gram negative bacteria than Gram positive bacteria. Inhibition zone diameters in the quantitative methods are found 15 and 16mm for Staphylococcus aureus, 9 and 7 mm for Bacillus cereus, respectively, for F4 and free juglone. Moreover, the MIC values for qualitative methods were found 31·5μgml-1 for two bacteria strains. It was found that the antibacterial activity of the juglone nanoparticles was higher and longer than the free juglone. Additionally, a similar antimicrobial effect with a lower juglone amount (obtained from controlled release study) indicates that nanoparticle formulation is more effective. The use of nanoparticle formulations of juglone in biological systems and applications could be more beneficial than its free form due to its toxicity.

Antioxidant activity and controlled drug delivery potential of tragacanth gum-cl- poly (lactic acid-co-itaconic acid) hydrogel

Tragacanth gum-cl-poly (lactic acid–co-itaconic acid) (TG-cl-p(LA-co-IA)) hydrogel is synthesized through graft copolymerization reaction using microwave assisted technique. The synthesized hydrogel was characterised using various analytical and characterization techniques such as FTIR, FESEM, XRD, TGA, TEM and SEM. It was observed that, the maximum percentage swelling (Ps) of the hydrogel was 311.61% after 6h at room temperature and 298.06% after 3h at 60°C and TG-cl-p(LA-co-IA) exhibited highest Amoxicillin loading (73%) in double distilled waterafter 24h. From the controlled release studies, it was evident that maximum drug release of about 96% took place at pH 2.2=after 6h. The synthesized hydrogel also showed mild antioxidant properties and 43.85% of free radical scavenging was occurred at a concentration of 640μg/mL and hence it can be effectively used to reduce the oxidative stresses. In addition to this, the antibacterial studies also showed that it is more effective against S. aureus.

Glucose-responsive zwitterionic dialdehyde starch-based micelles with potential anti-phagocytic behavior for insulin delivery

Both blood stability and glucose responsiveness for carriers are the most important issues in insulin controlled release studies. However, few reports focus on reducing macrophage response performance for drug carriers themselves. Zwitterionic self-assembled micelles mitigated recognition by immune cell has evolved to address this limitation. In this work, novel zwitterionic dialdehyde starch-based micelles, sulfobetaine (SB) as the hydrophilic shell, and 3-aminophenylboronic acid (APBA) as glucose-responsive groups to the dialdehyde starch (DAS) backbones (SB-DAS-APBA) with glucose-responsive behavior were developed. Insulin release from the nanocarriers is sensitive to the different concentration of the glucose, rapidly at the condition of 3 mg/mL of glucose at pH 7.4. Methyl thiazolyl tetrazoliumviability (MTT) assay confirmed that zwitterion micelles were cytobiocompatible and low cytotoxic activity with A549 cells. For comparison, PEGylation micelles, monomethyl ether (mPEG) as the hydrophilic shell, and APBA as glucose-responsive groups to the DAS backbones (mPEG-DAS-APBA), were also synthesized. Confocal laser scanning microscopy (CLSM) and flow cytometry results displayed that PEGylation and zwitterion coating micelles have different recognition processes in contact with macrophages. After 4 h, doxorubicin (Dox) fluorescence of the Dox-loaded mPEG-DAS-APBA micelle groups were mostly located in nuclei. However, SB-DAS-APBA micelle groups were slightly detected in both nuclei and cytosol. In addition, the fluorescence signals of mPEG-DAS-APBA micelles showed enhanced trend than that of SB-DAS-APBA micelles in macrophage cells. These results suggest that, as drug carriers, zwitterionic self-assembled micelles SB-DAS-APBA not only possessed glucose-responsive insulin delivery property, but also reduced macrophage response performance.

Innovative and high performance synthesis of microcapsules containing methyl anthranilate by microsuspension iodine transfer polymerization

In this research, preparations of polymer microcapsule encapsulated methyl anthranilate (MA) as an essential oil model by both microsuspension conventional radical polymerization (ms CRP) and microsuspension iodine transfer polymerization (ms ITP) using methyl methacrylate (MMA) and ethylene glycol dimethacrylate (EGDMA) copolymer as the polymer shell were studied. In the case of ms CRP, a large amount of free polymer particles nucleated in aqueous medium were obtained. Using ms ITP, the free polymer particle formation was significantly depressed. Iodoform (CHI3) as a chain transfer agent with 0.8 wt% relative to the monomer, such a phenomenon was not observed. Various emulsifiers (oleic acid, Span 80 and PEG 30 dipolyhydroxystearate (DPHS)) with low hydrophile–lipophile balance value were used to retain MA in the monomer droplets or polymerizing particles. DPHS is the most effective emulsifier to retain MA in microcapsules giving 58% encapsulation at 20 wt% of DPHS relative to MA. In addition, from the controlled release study, only 55 wt% of the encapsulated MA was released by 90 days. Polymer microcapsule encapsulated MA using an MMA-EGDMA copolymer shell with a high percentage of encapsulation and without free polymer particles was successfully prepared for the first time. Based on slow release of the encapsulated MA, the prepared microcapsules could be used in various applications. © 2017 Society of Chemical Industry

Magadiite as a support for the controlled release of herbicides

Diuron and 2,4-dichlorophenoxyacetic acid were intercalated into layered silicate magadiite and the presence of anchored herbicides within the lamellas was confirmed by Fourier transform infrared spectroscopy. X-ray diffraction patterns and surface area analysis showed that the intercalation of herbicides decreased basal lamellar spacing and the surface area of the silicate. According to the results obtained from surface charge analysis, the main interactions between magadiite and the herbicides were mediated by hydrogen bond formation. Controlled release studies demonstrated that the delivery of the herbicides occurred substantially faster at pH 9, while the difference in delivery rates at pH 1 and pH 4.6 (the point of zero charge) was far less marked, although release at the more acidic pH was slightly quicker. The use of magadiite as a herbicide support shows great potential for the development of controlled release systems and will contribute to more sustainable forms of weed control.

Functionalized SBA-15 for controlled release of poorly soluble drug, Erythromycin

SBA-15 was functionalized by 12-tungstophosphoric acid followed by loading of poorly water soluble drug, Erythromycin and Characterized by various physicochemical techniques such as TGA, FT-IR, Nitrogen adsorption-desorption, XRD and TEM. In-vitro controlled release studies of Erythromycin in Simulated Body Fluid were carried out under stirring as well as static conditions. In order to see the influence of inorganic moiety on release rate of drug, study was also carried out with Erythromycin loaded unfunctionalized SBA-15. A study on release mechanism and release kinetics using Higuchi model, Koresmeyer-Peppas model and Extended kinetic model shows that 12-tungstophosphoric acid has significant influence on the release rate of Erythromycin.

Development of docetaxel-loaded PEG–PLA nanoparticles using surfactant-free method for controlled release studies

ABSTRACTDocetaxel (DTX)-loaded poly(ethylene glycol)–poly(D,L-lactide) is prepared by nanoprecipitation method in the absence of any surfactants. The average particle size of the copolymer was found to be 101 nm. The drug entrapment efficiency (%) and drug loading (%) of polymer were found to be 9.471 ± 0.047 and 94.71 ± 0.466, respectively. The in vitro drug release characteristics show the controlled release of 98% of docetaxel in 72 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis measured in terms of cleaved Poly(ADP-ribose) Polymerase (PARP) and cleaved caspase-3 protein expression shows that the copolymer has better cytotoxicity effect and apoptosis in comparison to free DTX in HeLa cells.

Comparative In Vitro Controlled Release Studies on the Chronobiotic Hormone Melatonin from Cyclodextrins-Containing Matrices and Cyclodextrin: Melatonin Complexes

A series of hydrophilic matrix tablets was prepared and tested with respect to their ability to release the hormone melatonin in a controlled manner, in order to alleviate sleep onset and sleep maintenance dysfunctions. Besides the active ingredient, the tablets were comprised of combinations of the following: HPMC K 15M, low viscosity sodium alginate, microcrystalline cellulose (Avicel PH 102), magnesium stearate, and the cyclodextrins, α-CD, β-CD, γ-CD, HP-β-CD, sulfated β-CD, HP-α-CD and HP-γ-CD, and MLT (guest):CD (host) complexes of the above cyclodextrins, in 1:1 ratio. The controlled release studies were conducted in two aqueous dissolution media at pH 1.2 and 7.4. The stoichiometry of the formed complexes was examined by applying the continuous variation method (Job plot), while the stability constants were calculated by monitoring the spectrophotometric properties of free and CD-encapsulated melatonin (UV-Vis). Host-guest interactions were studied by Nuclear Magnetic Resonance (NMR) spectroscopy. The dissolution data suggest that melatonin is released faster from the MLT:CD complexes than from the rest matrix systems. This enhancement in the dissolution rate and the % release of melatonin from the complexes is due to the increased solubility of the MLT:CD complexes.

Competitive-Binding Activated Supramolecular Nanovalves Based on β-Cyclodextrin Complexes

Competitive binding activated nanovalves (CBAN) with on-demand activation capability are fabricated through switching from host-guest complexation to decomplexation upon the introduction of competitive guest (C-guest) molecules. Guest molecules of pyrene or naphthalene are used to associate with β-cyclodextrin (β-CD) host to form supramolecular complexes. These supramolecular conjugations were assembled on the surface of mesoporous silica nanoparticles (MSNs), which played a role of “nanovalve” for blocking the nanopores. For the activation of nanovalves, C-guest of 1-adamantanamine hydrochloride (Ad), was added to dissociate formerly assembled complex by competitive binding with host β-CD. In controlled release study, the fabricated CBAN was stable at “Off” state for preventing cargo release, and able to release the cargo efficiently at “On” state. Moreover, the competitive binding process was also investigated by using fluorescein isothiocyanate modified β-CD. It was found that the shift of host-guest complexation equilibrium by C-guest activates the CBAN. These results would shed lights on the development of novel supramolecular nanovalves.

Polysaccharide blended whey protein isolate-(WPI) hydrogels: A physicochemical and controlled release study

Design and characterization of composite whey protein isolate (WPI) hydrogels are gaining interest due to their utilization as controlled delivery matrices for bioactive agents. In this study, black carrot extract (BC) loaded composite WPI hydrogels, containing xanthan (XN), pectin (PC) and gum tragacanth (GT) were prepared by conventional water bath (CV) and infrared (IR) assisted microwave heating (MW). Release and swelling experiments were conducted at pH 7.0 phosphate buffer solution for 24 h. Highest swelling ratio (SR) was observed at CV XN hydrogels and only XN hydrogels showed a distinct increase in SR (17.85%) with respect to WPI hydrogels containing no additional polymer (10.55%) (p < 0.05). CV WPI hydrogels having no added polysaccharide showed the highest release percent (77.81%). CV PC, XN and GT hydrogels with release ratios of 37.15%, 32.79% and 29.39%, respectively, were capable of retarding release with respect to sole WPI hydrogels (p < 0.05). MW increased the release rates of all polymer added hydrogels. Nuclear Magnetic Resonance (NMR) relaxometry was used to understand the polymer-water interactions in the samples. Therefore, transverse relaxation times (T2) and self-diffusion coefficients (SDC) of each hydrogel were measured. Increasing T2 and SDC values of CV XN samples were associated with better gel characteristics. Scanning electron microscope (SEM) images revealed the microstructural differences between the heating and polymer types. Mathematical modelling of release behaviors of hydrogels was also conducted to estimate diffusion coefficients. Moreover, this study introduces the effects of MW-IR heating on the physiochemical and controlled release behavior of WPI-GT composite hydrogels for the first time.