Stimulus triggered release of actives from composite microcapsules based on sporopollenin from Lycopodium clavatum.

Smart drug delivery systems (SDDSs) are a paradigm shift in drug delivery, particularly in microencapsulation technology where the drug is released in response to an internal and/or external stimulus. In this study, a smart microencapsulation platform was developed using three different types of stimuli triggered release of a model active (rhodamine 6G) from sporopollenin from Lycopodium clavatum. Triggers were based on pH-, thermal- and near infrared light-sensitive polymer composition. Carbopol nanogel and methylcellulose were used as responsive aqueous polymers for pH and thermally triggered release, respectively. Methylcellulose loaded with active and gold nanoparticles was used for photothermal triggered release. The formulations were encapsulated into the empty cores of sporopollenin microcapsules using the compressed tablet technique. The pH triggered release of the active was achieved above pH 7, which was mediated by the swelling of the carbopol nanogel that forced its way out of the elastic trilite scars of the sporopollenin. Results from measuring the active fluorescent intensity and its content over time confirmed the crucial role of carbopol in the pH triggered release. For the thermo-sensitive polymer methylcellulose, it was found that the release of the active from methylcellulose loaded sporopollenin was triggered upon heating the system reaching 90% whereas it levelled out at 40% for methylcellulose-free sporopollenin. The maximum amount of active was released at around 55 °C, where the sol-gel transition of the methylcellulose starts. Photothermally triggered release using near infrared (NIR) laser revealed that the amount of active released from sporopollenin loaded with both gold nanoparticles and methylcellulose was approximately four times higher than that from sporopollenin loaded with methylcellulose/active only, confirming the key role of gold nanoparticles in the release via photothermal heating of the polymer formulation.

Natural sporopollenin microcapsules: biological evaluation and application in regulating hepatic toxicity of diclofenac sodium in vivo.

Diclofenac sodium (DIC) is a pain reliever and anti-nociceptive medication. Significant limitations of DIC treatment stem from its adverse effects. This study investigates the feasibility of using natural Lycopodium clavatum sporopollenin (LCS) microcapsules loaded with DIC to mitigate the hepatotoxicity associated with DIC treatment. In addition, LCS microcapsules were tracked in the blood, stomach, small intestine, and feces of rats to demonstrate their morphological integrity and uptake behavior. Four groups (6 per group) of adult male albino rats were administered normal saline (control), empty LCS (30 mg kg-1), plain DIC (10 mg kg-1), and DIC-loaded LCS (40 mg kg-1) orally for seven consecutive days. The first comprehensive histological examination of the rat stomach demonstrated the robustness and bioadhesion ability of LCS under severe conditions. The findings suggested that these versatile microcapsules are unlikely to be digested in the gastrointestinal tract (GIT). The administration of DIC-loaded LCS was found to play a potential protective role in regulating DIC-induced substantially increased serum levels of transaminases, alkaline phosphatase, total bilirubin, and pro-inflammatory cytokines. In addition, DIC-loaded LCS restored the antioxidant enzymes, DNA damage, and liver histological architecture abnormalities caused by DIC. Microencapsulation of DIC into pollen-derived biomaterials could be employed as an efficient platform with enough safety coverage on rat liver, pending further clinical studies.

Pollen-derived microcapsules for aspirin microencapsulation: in vitro release and physico-chemical studies.

Aspirin, also known as acetylsalicylic acid (ASA), is one of the most crucial therapies needed and/or used in a basic health system. Using biocompatible materials to encapsulate ASA would improve its therapeutic efficacy and reduce its side effects via controlled release in physiological environments. Consequently, we explore in this study the feasibility of encapsulation of ASA into robust Lycopodium clavatum L. sporopollenin (LCS) microcapsules. After extracting sporopollenin from their natural micrometer-sized raw spores, the physico-chemical features of the extracted sporopollenin, pure ASA, and sporopollenin loaded with ASA were characterised using various methods, including optical microscopy, Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible (UV-vis.) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Additionally, we demonstrate the in vitro release profile of ASA in a triggered gastrointestinal environment utilizing kinetics analysis to investigate the mechanism of release. The LCS microcapsules were found to be excellent encapsulants for the crucial ASA drug and achieved controlled in vitro release, that would enable further investigations to rationally design versatile controlled delivery platforms.

Encapsulation of folic acid (vitamin B9) into sporopollenin microcapsules: Physico-chemical characterisation, in vitro controlled release and photoprotection study.

Folic acid (FA) is a crucial vitamin for all living creatures. However, it is susceptible to degradation under pH, heat, ultraviolet (UV) and day sunlight conditions, resulting in lowering its bioavailability. Therefore, a versatile protective encapsulation system for FA is highly required to overcome its inherent instability. We report the use of the robust Lycopodium clavatum sporopollenin (LCS) microcapsules, extracted from their natural micrometer-sized raw spores, for FA microencapsulation. The physico-chemical characterisation of the LCS microcapsules are comprehensively investigated before and after the microencapsulation using SEM, elemental, CLSM, FTIR, TGA/DTG and XRD analyses, revealing a successful FA encapsulation within the LCS in an amorphous form. The phenylpropanoid acids, responsible for the UV protection and the autofluorescence of the LCS, were found in the LCS as evidenced by FTIR analysis. TGA/DTG results revealed that the hemi-cellulose and cellulose are the major component of the LCS. A controlled and sustained release of FA from FA-loaded LCS were achieved where the release profile of FA-loaded LCS was found to be pH-dependent. The percentages of cumulative FA released after 10 h at 37 ± 0.5 °C were 45.5% and 76.1% in pH 1.2 and 7.4, respectively, ensuring controlled and slow release in simulated physiological conditions. The FA release kinetic studies indicated the prevalence of the Fickian diffusion mechanism in pH 1.2, while anomalous non-Fickian transport was ascribed for FA release in pH 7.4. The in vitro cytotoxicity assay revealed that the obtained formulations were biocompatible against the human skin fibroblast (HSF) cell line. The versatile LCS microcapsules exhibited intriguing photostability for FA under UV or sunlight irradiation. Concretely, the obtained FA sustained delivery and photoprotection properties of these LCS microcapsules validate their multifunctional characteristics, opening up intriguing applications in oral and topical drug delivery as well as in food industry.

Sustained In Vitro and In Vivo Delivery of Metformin from Plant Pollen-Derived Composite Microcapsules.

We developed a dual microencapsulation platform for the type 2 diabetes drug metformin (MTF), which is aimed to increase its bioavailability. We report the use of Lycopodium clavatum sporopollenin (LCS), derived from their natural spores, and raw Phoenix dactylifera L. (date palm) pollens (DPP) for MTF microencapsulation. MTF was loaded into LCS and DPP via a vacuum and a novel method of hydration-induced swelling. The loading capacity (LC) and encapsulation efficiency (EE) percentages for MTF-loaded LCS and MTF-loaded DPP microcapsules were 14.9% ± 0.7, 29.8 ± 0.8, and 15.2% ± 0.7, 30.3 ± 1.0, respectively. The release of MTF from MTF-loaded LCS microcapsules was additionally controlled by re-encapsulating the loaded microcapsules into calcium alginate (ALG) microbeads via ionotropic gelation, where the release of MTF was found to be significantly slower and pH-dependent. The pharmacokinetic parameters, obtained from the in vivo study, revealed that the relative bioavailability of the MTF-loaded LCS-ALG beads was 1.215 times higher compared to pure MTF, following oral administration of a single dose equivalent to 25 mg/kg body weight MTF to streptozotocin (STZ)-induced diabetic male Sprague-Dawley rats. Significant hypoglycemic effect was obtained for STZ-induced diabetic rats orally treated with MTF-loaded LCS-ALG beads compared to control diabetic rats. Over a period of 29 days, the STZ-induced diabetic rats treated with MTF-loaded LCS-ALG beads showed a decrease in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides, cholesterol, and low-density lipoprotein-cholesterol (LDL-C) levels, as well as an increase in glutathione peroxidase (GPx) and a recovery in the oxidative stress biomarker, lipid peroxidation (LPx). In addition, histopathological studies of liver, pancreas, kidney, and testes suggested that MTF-loaded LCS-ALG beads improved the degenerative changes in organs of diabetic rats. The LCS-ALG platform for dual encapsulation of MTF achieved sustained MTF delivery and enhancement of bioavailability, as well as the improved biochemical and histopathological characteristics in in vivo studies, opening many other intriguing applications in sustained drug delivery.

Microwave assisted one-pot green synthesis of cinnoline derivatives inside natural sporopollenin microcapsules.

We present a green and efficient approach for the synthesis of novel cinnoline derivatives inside natural Lycopodium clavatum sporopollenin (LCS) microcapsules via a one-pot microwave (MW) assisted reaction for the first time. We also propose the concept that the robust micrometre-sized sporopollenin microcapsules can act as MW microreactors. We demonstrate the feasibility of this concept by in situ synthesising 8-hydroxy-7-nitro-6-(3-nitrophenyl)-3-oxo-2-(p-tolyl)-2,3,5,6-tetrahydrocinnoline-4-carbonitrile inside the LCS microcapsules via a microwave (MW) assisted reaction of ethyl 5-cyano-4-methyl-6-oxo-1-(p-tolyl)-1,6-dihydropyridazine-3-carboxylate with 1-nitro-2-phenylethylene in the presence of piperidine as a base at 100 °C for 20 minutes. The LCS microparticles are extensively characterised before and after the MW induced reaction using several techniques. The formation of the cinnoline compound inside the LCS microcapsules is confirmed by laser scanning confocal microscopy (LSCM), X-ray diffraction (XRD) and fourier-transform infrared spectroscopy (FTIR) analyses. Using liquid chromatography-mass spectrometry (LCMS) analyses, we show that the structural integrity of the cinnoline compound, recovered from the cinnoline loaded (cinn-loaded) LCS, is preserved. The pure cinnoline is found to show promising optical properties with two λ max absorption peaks at 310 and 610 nm. Both the pure cinnoline and cinn-loaded LCS show promising antibacterial activity against Pseudomonas aeruginosa (Gram-negative) and Bacillus cereus (Gram-negative) human pathogenic bacterial strains. The successful MW induced reaction of the prominent cinnoline derivative inside the biocompatible LCS microreactors can open up intriguing applications in materials and pharmaceutical sciences.

Encapsulation of erythromycin and bacitracin antibiotics into natural sporopollenin microcapsules: antibacterial, cytotoxicity, in vitro and in vivo release studies for enhanced bioavailability.

Nature produces large quantities of superbly complex and highly reliable microcapsules. The micrometre-sized Lycopodium clavatum spores are one example of these robust capsules. The encapsulation of erythromycin (EM) and bacitracin (BAC) antibiotics into the Lycopodium clavatum sporopollenin (LCS) extracted from these spore species is explored for the first time. The LCS microparticles are extensively characterised before and after loading using SEM, CLSM, TGA and FTIR techniques. The loading capacity and entrapping efficiency of EM were 16.2 and 32.4%, respectively. The antibacterial activities of pure antibiotics, empty LCS and the antibiotic-loaded LCS were evaluated against Staphylococcus aureus (Gram-positive), Pseudomonas aeruginosa (Gram-negative), and Klebsiella pneumoniae (Gram-negative) human pathogenic bacterial strains. A remarkable increase in the antibacterial fold activity of both EM- and BAC-loaded LCS compared to that of the pure antibiotics is observed. Crucial for drug delivery applications, empty LCS, EM- and BAC-loaded LCS were found to be nontoxic against human epithelial colorectal adenocarcinoma cells Caco-2 as revealed by the cytotoxicity evaluation. The in vitro release mechanism of EM in pH 7.4 showed a deviation from Fick's law. In vivo release of EM from EM-loaded LCS (an oral dose of 50 mg kg-1) revealed high values of the area under the plasma concentration-time curve (AUC0-6 h and AUC0-∞ were 1620 and 2147 µg h L-1, respectively) indicative of the enhanced EM bioavailability. The successful loading of antibiotics into the nontoxic LCS and the enhanced bioavailability can open up intriguing applications in oral and topical drug delivery strategies.

Strained arrays of colloidal nanoparticles: conductance and magnetoresistance enhancement.

Colloidal nanoparticles are very popular as building blocks of functional arrays for electronic and optical applications. However, there is a problem in achieving electrical conductivity in such nanoarrays due to their molecular shells. These shells, which are inherent to colloidal particles, physically separate the nanoparticles in an array and act as very effective insulators. Post-assembly thinning of the shells is therefore required to enhance the array conductivity to a sensible value. Here, we introduce a conceptually new approach to the thinning, using compressive stress applied to the array by the supporting matrix. The stress arises from polymerization-induced shrinkage of the matrix as an integral step during device assembly. Using arrays of oleic-acid-covered magnetite nanoparticles in conjunction with an HDDA-polymer (HDDA: 1,6-hexanediol diacrylate) matrix, we have achieved a significant steady current in the array along with an unprecedented value of the magnetoresistance. Our results serve as a proof-of-concept for other colloidal nanoparticles.

Fabrication of magnetically-functionalized lens- and donut-shaped microparticles by a surface-formation technique.

We report a simple method for the preparation of magnetically-functionalized lens-like and donut-shaped polymeric microparticles, based on spreading a magnetite-doped paraffin-polymer solution at the air/water interface in the presence of an external magnetic field. We examine the parameters that affect the particle morphology and interfacial aggregation behaviour.

Contact angles in relation to emulsions stabilised solely by silica nanoparticles including systems containing room temperature ionic liquids.

We report measured and calculated oil-ionic liquid, water-ionic liquid and oil-water contact angles on silica surfaces which have been hydrophobised to different extents by silanisation. Based on the idea that the contact angle formed by a liquid-liquid interface with a particle adsorbed at that interface is a key determinant of the strength of particle adsorption and the tendency of the adsorbed particle film to curve, we correlate the contact angle data with the phase inversion points and stabilities of the corresponding particle-stabilised emulsions.

Novel emulsions of ionic liquids stabilised solely by silica nanoparticles.

We have successfully prepared a series of novel stable emulsions, of both simple and multiple types, containing ionic liquids and stabilised solely by silica nanoparticles.

Ellipsometric Study of Monodisperse Silica Particles at an Oil-Water Interface.

Results are reported for ellipsometric measurements of hydrophobized monodisperse silica particles, with a diameter of about 25 nm, spread at the toluene-water interface. Theoretical values for the ellipsometric parameters are derived by treating the particles as a core-shell model and performing integrations of the refractive index profile through the interface using Drude's equations. With justifiable choices of the fixed parameters for the system, the agreement is good between measured and calculated values for the ellipsometric parameter Δ as a function of the amount of silica particles added to the interface. However, the results at high particle concentration at the interface are consistent either with coverage greater than a close-packed monolayer or with a monolayer with corrugations whose amplitude is less than the radius of the particles. The results show that this is not a suitable method for the determination of the contact angle of the particles at the oil-water interface.