Hydrogel- and Nanocomposite-Based Drug-Delivery Strategies in the Treatment of Vaginal Infections.

The reproductive health of women is governed by an optimal balance in the host-microbiota interaction. Depletion of the beneficial vaginal microflora caused by depletion of Lactobacillus species and increased proliferation of pathogens results in gynaecological infections. Among women of reproductive age, vaginal infections are increasingly prevalent. Attaining therapeutic efficacy using conventional formulations remains a challenge as vaginal fluids quickly remove or dilute the therapeutic formulations. Hydrogels have been widely exploited for targeted delivery of therapeutics directly into the vaginal mucus. With a careful choice of polymers (natural, synthetic, or semisynthetic), hydrogels with specific properties, such as stimuli responsiveness, antimicrobial, and muco-adhesiveness, can be tailored for higher therapeutic efficacy. In this review, the advances in hydrogel strategies for the treatment of vaginal infections are presented with emphasis on the types and properties that play a significant role in vaginal drug delivery systems.

Seamless Integration of Conducting Hydrogels in Daily Life: From Preparation to Wearable Application.

Conductive hydrogels (CHs) have received significant attention for use in wearable devices because they retain their softness and flexibility while maintaining high conductivity. CHs are well suited for applications in skin-contact electronics and biomedical devices owing to their high biocompatibility and conformality. Although highly conductive hydrogels for smart wearable devices are extensively researched, a detailed summary of the outstanding results of CHs is required for a comprehensive understanding. In this review, the recent progress in the preparation and fabrication of CHs is summarized for smart wearable devices. Improvements in the mechanical, electrical, and functional properties of high-performance wearable devices are also discussed. Furthermore, recent examples of innovative and highly functional devices based on CHs that can be seamlessly integrated into daily lives are reviewed.

Effects of Different Parts of the Okra Plant (Abelmoschus esculentus) on the Phytosynthesis of Silver Nanoparticles: Evaluation of Synthesis Conditions, Nonlinear Optical and Antibacterial Properties.

In this work, stable and spherical silver nanoparticles (AgNPs) were synthesized in situ from silver salt (silver nitrate) using the aqueous extract of the okra plant (Abelmoschus esculentus) at room temperature and ambient pH conditions. The influences of different parts of the plant (such as the leaves, stems, and pods) on the chemical-reducing effectiveness of silver nitrate to silver nanoparticles were investigated. The aqueous extract of the leaves was found to be more effective in the chemical reduction of silver nanoparticles and in stabilizing them at the same time. The silver nanoparticles produced were stable and did not precipitate even after storage for 1 month. The extract of the stem was less effective in the reduction capacity followed by the extract of the pods. The results indicate that the different amounts of phytochemicals present in the leaves, stems, and pods of the okra plant are responsible for the chemical reduction and stabilizing effect. The silver nanoparticles were characterized by UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX). The surface plasmon resonance (SPR) peak at 460 nm confirmed the formation of silver nanoparticles. The nanoparticles were spherical with an average size of 16 nm and polycrystalline with face-centered cubic (fcc) structures. The z-scan technique was used to study the nonlinear refraction and absorption coefficients of AgNPs at wavelengths of 488 and 514 nm under C.W. mode excitation. The nonlinear refraction index and nonlinear absorption coefficients were calculated in the theoretical equations in the experimental data. The antibacterial properties of the nanoparticles were evaluated against Gram-positive and Gram-negative bacteria.

An Exploration of Nanoparticle-Based Diagnostic Approaches for Coronaviruses: SARS-CoV-2, SARS-CoV and MERS-CoV.

The wildfire-like spread of COVID-19, caused by severe acute respiratory syndrome-associated coronavirus-2, has resulted in a pandemic that has put unprecedented stress on the world's healthcare systems and caused varying severities of socio-economic damage. As there are no specific treatments to combat the virus, current approaches to overcome the crisis have mainly revolved around vaccination efforts, preventing human-to-human transmission through enforcement of lockdowns and repurposing of drugs. To efficiently facilitate the measures implemented by governments, rapid and accurate diagnosis of the disease is vital. Reverse-transcription polymerase chain reaction and computed tomography have been the standard procedures to diagnose and evaluate COVID-19. However, disadvantages, including the necessity of specialized equipment and trained personnel, the high financial cost of operation and the emergence of false negatives, have hindered their application in high-demand and resource-limited sites. Nanoparticle-based methods of diagnosis have been previously reported to provide precise results within short periods of time. Such methods have been studied in previous outbreaks of coronaviruses, including severe acute respiratory syndrome-associated coronavirus and middle east respiratory syndrome coronavirus. Given the need for rapid diagnostic techniques, this review discusses nanoparticle use in detecting the aforementioned coronaviruses and the recent severe acute respiratory syndrome-associated coronavirus-2 to highlight approaches that could potentially be used during the COVID-19 pandemic.

Persistence of Ebola virus in semen among Ebola virus disease survivors in Sierra Leone: A cohort study of frequency, duration, and risk factors.

BACKGROUND: Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone. METHODS AND FINDINGS: In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%-82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%-34.2%), and at 360 days, 6.0% (95% CI 3.1%-10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%-19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose-response pattern, where the youngest men (≤25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26-35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%-50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness. CONCLUSIONS: In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time.

"You have to find a caring man, like your father!" gendering sickle cell and refashioning women's moral boundaries in Sierra Leone.

Most research on sickle cell disorders has tended to be gender-blind. This qualitative study undertaken in 2018, explores if and how sickle cell disorders become gendered in Sierra Leone through the analytical framework of a feminist ethics of care. It argues that women have to navigate moral blame when they have children with the condition. At the same time women refashion moral boundaries so that gendered norms around childhood and parenting for such children become suspended, in favour of creation of careful spaces. Parental fears of physical and sexual violence mean that gendered sexual norms are enforced for teenage boys as they are encouraged into early adulthood. In contrast, girls are kept in enforced ignorance about the consequences of sickle cell for reproduction and are encouraged to delay motherhood. This is because, as women relate, relationships and giving birth are fraught with embodied dangers and risks of violence.

Enhanced transfection of a macromolecular lignin-based DNA complex with low cellular toxicity.

Cationic polymers remain attractive tools for non-viral gene transfer. The effectiveness of these vectors rely on the ability to deliver plasmid DNA (pDNA) into the nucleus of cells. While we have previously demonstrated the potential of Lignin-PGEA-PEGMA as a non-viral gene delivery vector, alterations of cellular phenotype and cytotoxicity were observed post transfection. The present study aims to explore transfection conditions for high efficiency and low toxicity of the Lignin-PGEA-PEGMA based gene delivery system. Cellular toxicity was significantly reduced by using the centrifugation protocol, which enables rapid deposition of DNA complexes. Replacement of media post centrifugation resulted in minimal exposure of cells to excess polymers, which were toxic to cells. At an optimized DNA amount (500-750 ng) and molar ratios of nitrogen (N) in polymer to phosphate (P) in pDNA (N/P = 30-40), with the use of a novel transfection enhancer that facilitates endosomal escape and nuclear trafficking, the efficiency of gene delivery was increased significantly 24 h post transfection. The present study demonstrated an appropriately optimized protocol that enabled the utility of a novel cationic polymer blend with a mixture of fusogenic lipids and a histone deacetylate inhibitor in non-viral transfection, thereby providing an attractive alternative to costly commercial gene carriers.

Engineering PCL/lignin nanofibers as an antioxidant scaffold for the growth of neuron and Schwann cell.

Antioxidant is critical for the successful of nerve tissue regeneration, and biomaterials with antioxidant activity might be favorable for peripheral nerve repair. Lignin, a biopolymer from wood with excellent antioxidant properties, is still "unexplored" as biomaterials. To design an antioxidative bioscaffold for nerve regeneration, here we synthesized lignin-polycaprolactone (PCL) copolymers via solvent free ring-opening polymerization (ROP). Then such lignin-PCL copolymers were incorporated with PCL and engineered into nanofibrous scaffolds for supporting the growth of neuron and Schwann cell. Our results showed that the addition of lignin-PCL enhanced the mechanical properties of PCL nanofibers and endowed them with good antioxidant properties (up to 98.3 ±â€¯1.9% free radical inhibition within 4 h). Cell proliferation assay showed that PCL/lignin-PCL nanofibers increased cell viability compared to PCL fibers, especially after an oxidative challenge. Moreover, Schwann cells and dorsal root ganglion (DRG) neurons cultured on the nanofibers to assess their potential for nerve regeneration. These results suggested that nanofibers with lignin copolymers promoted cell proliferation of both BMSCs and Schwann cells, enhanced myelin basic protein expressions of Schwann cells and stimulated neurite outgrowth of DRG neurons. In all, these sustainable, intrinsically antioxidant nanofibers may be a potential candidate for nerve TE applications.

Stimuli-Responsive Cationic Hydrogels in Drug Delivery Applications.

Stimuli-responsive, smart, intelligent, or environmentally sensitive polymers respond to changes in external stimuli such as pH, temperature, ionic strength, surfactants, pressure, light, biomolecules, and magnetic field. These materials are developed in various network architectures such as block copolymers, crosslinked hydrogels, nanogels, inter-penetrating networks, and dendrimers. Stimuli-responsive cationic polymers and hydrogels are an interesting class of "smart" materials that respond reversibly to changes in external pH. These materials have the ability to swell extensively in solutions of acidic pH and de-swell or shrink in solutions of alkaline pH. This reversible swelling-shrinking property brought about by changes in external pH conditions makes these materials useful in a wide range of applications such as drug delivery systems and chemical sensors. This article focuses mainly on the properties of these interesting materials and their applications in drug delivery systems.

Myoglobin and α-Lactalbumin Form Smaller Complexes with the Biosurfactant Rhamnolipid Than with SDS.

Biosurfactants (BSs) attract increasing attention as sustainable alternatives to petroleum-derived surfactants. This necessitates structural insight into how BSs interact with proteins encountered by current chemical surfactants. Thus, small-angle x-ray scattering (SAXS) has been used for studying the structures of complexes made of the proteins α-Lactalbumin (αLA) and myoglobin (Mb) with the biosurfactant rhamnolipid (RL). For comparison, complexes between αLA and the chemical surfactant sodium dodecyl sulfate (SDS) were also investigated. The SAXS data for pure RL micelles can be described by prolate core-shell structures with a core radius of 7.7 Å and a shell thickness of 12 Å, giving an aggregation number of 11. The small core radius is attributed to RL's complex hydrophobic tail. Data for the αLA-RL complex agree with a 12-molecule micelle with a single protein molecule in the shell. For Mb-RL, the analysis gives complexes of two connected micelles, each containing 10 RL and one protein in the shells. αLA-RL and Mb-RL form surfactant-saturated complexes above 5.6 and 4.7 mM RL, respectively, leaving the remaining RL in free micelles. The SAXS data for SDS agree with oblate-shaped micelles with a core of 20 Å, core eccentricity 0.7, and shell thickness of 5.45 Å, with an aggregation number of 74. The αLA-SDS complexes contain a prolate micelle with a core radius of 11-14 Å and a shell of 8-12 Å with up to 3 αLA per particle and up to 43 SDS per αLA, both considerably larger than for RL. Unlike the RL-protein complexes, the number of surfactant molecules in αLA-SDS complexes increases with surfactant concentration, and saturate at higher surfactant concentrations than αLA-RL complexes. The results highlight how RL and SDS follow similar overall rules of self-assembly and interactions with proteins, but that differences in the strength of protein-surfactant interactions affect the formed structures.

Safety, productivity and predicted contribution of a surgical task-sharing programme in Sierra Leone.

BACKGROUND: Surgical task-sharing may be central to expanding the provision of surgical care in low-resource settings. The aims of this paper were to describe the set-up of a new surgical task-sharing training programme for associate clinicians and junior doctors in Sierra Leone, assess its productivity and safety, and estimate its future role in contributing to surgical volume. METHODS: This prospective observational study from a consortium of 16 hospitals evaluated crude in-hospital mortality over 5 years and productivity of operations performed during and after completion of a 3-year surgical training programme. RESULTS: Some 48 trainees and nine graduated surgical assistant community health officers (SACHOs) participated in 27 216 supervised operations between January 2011 and July 2016. During training, trainees attended a median of 822 operations. SACHOs performed a median of 173 operations annually. Caesarean section, hernia repair and laparotomy were the most common procedures during and after training. Crude in-hospital mortality rates after caesarean sections and laparotomies were 0·7 per cent (13 of 1915) and 4·3 per cent (7 of 164) respectively for operations performed by trainees, and 0·4 per cent (5 of 1169) and 8·0 per cent (11 of 137) for those carried out by SACHOs. Adjusted for patient sex, surgical procedure, urgency and hospital, mortality was lower for operations performed by trainees (OR 0·47, 95 per cent c.i. 0·32 to 0·71; P < 0·001) and SACHOs (OR 0·16, 0·07 to 0·41; P < 0·001) compared with those conducted by trainers and supervisors. CONCLUSION: SACHOs rapidly and safely achieved substantial increases in surgical volume in Sierra Leone.

Utilising inorganic nanocarriers for gene delivery.

The delivery of genetic materials into cells to elicit cellular responses has been extensively studied by biomaterials scientists globally. Many materials such as lipids, peptides, viruses, synthetically modified cationic polymers and certain inorganic nanomaterials could be used to complex the negatively charged plasmids and deliver the formed package into cells. The recent literature on the delivery of genetic materials utilising inorganic nanoparticles is carefully examined in this review. We have picked out the most relevant references and concisely summarised the findings with illustrated examples. We further propose alternative approaches and suggest future pathways towards the practical use of multifunctional nanocarriers.

Synthesis and Properties of New "Stimuli" Responsive Nanocomposite Hydrogels Containing Silver Nanoparticles.

Hydrogel nanocomposites containing silver nanoparticles of size 15⁻21 nm were prepared by diffusion and in-situ chemical reduction in chemically crosslinked polymers based on N-acryloyl-N'-ethyl piperazine (AcrNEP) and N-isopropylacrylamide (NIPAM). The polymer chains of the hydrogel network offered control and stabilization of silver nanoparticles without the need for additional stabilizers. The presence of silver nanoparticles and their size was quantified by UV-Vis absorption spectroscopy and scanning electron microscopy. The nanocomposite hydrogels were responsive to pH and temperature changes of the external environment. The equilibrium weight swelling ratio of the hydrogel nanocomposite was lower in comparison with the precursor hydrogel. Silver nanoparticles present in the nanocomposite offered additional physical crosslinking which influenced media diffusion and penetration velocity. The release of silver nanoparticles from the hydrogel matrix in response to external pH changes was studied. The rate of release of silver nanoparticles was higher in a solution of pH 2.5 due to maximum swelling caused by ionization of the gel network. No significant release of nanoparticles was observed in a solution of pH 7.

Characterization and degradation of elastomeric four-armed star copolymers based on caprolactone and L-lactide.

Although biodegradable polymers have found extensive applications in medical areas, there are limited reports that show elastomeric behavior. In this work, a biodegradable, elastomeric polymer is demonstrated from a four-armed star copolymer. With a fixed middle core composition, comprising caprolactone (CL) and L-lactide (LA), an elastomer is obtained by increasing the polylactide (PLA) end block lengths to obtain sufficient end block crystallinity. This increase suppressed the middle core's crystallinity yet ensured cocrystallization of the PLA ends of individual star copolymer chains to form a three-dimensional network via physical crosslinking. Cyclic and creep test of the star copolymers showed that at least 75% of recovery was achieved. Degradation study of the copolymer showed that degradation first occurred in the caprolactone-co-lactide (CLLA) core, followed by degradation in the PLA ends. Chain scission in the middle core resulted in immediate formation of CL crystals within the core and increased crystallinity over time, in both CLLA core and PLA ends.

Synthesis and characterization of nanogels of poly(N-isopropylacrylamide) by a combination of light and small-angle X-ray scattering.

Thermo-responsive crosslinked nanogels of N-isopropylacrylamide (NIPAM) were synthesized by emulsion polymerization and the size was varied using different concentrations of surfactant (sodium dodecyl sulfate, SDS) in the polymerization process. The collapse behavior of the nanogels at the lower critical solution temperature at around 32 °C was investigated by dynamic light scattering, and by combined static light scattering (SLS) and small-angle X-ray scattering (SAXS). The combined data from SLS and SAXS were analyzed by a model for the nanogels which at intermediate temperatures included a central core and a more diffuse outer layer describing pending polymer chains with a low degree of cross linking. In the expanded state, the particles were modeled with a single component with a broad graded surface. In the collapsed state the nanogels were modeled as homogeneous and relatively compact particles. The amount of surfactant used had a profound effect on the final size of the nanogels owing to the phenomenon of colloidal stabilization of the emulsion droplets during polymerization. The combination of SLS and SAXS as applied to the nanogels is an attractive method for particle characterization as it spans a very large range of scattering vector from q = 0.0004 to 0.22 Å(-1).

Nucleation of an oil phase in a nonionic microemulsion-containing chlorinated oil upon systematic temperature quench.

A clear and stable nonionic model microemulsion consisting of pentaoxyethylene glycol dodecyl ether (C(12)E(5)), water, and 1-chlorotetradecane (CLTD) was prepared. This system was subjected to a systematic temperature quench (perturbation out of equilibrium) in steps of 1.0 degrees C from 20.4 to 15.3 degrees C in the unstable region of its phase diagram. The change in turbidity (for droplet volume fractions of 0.02 and 0.08) and hydrodynamic radius (R(h)) (for a droplet volume fraction of 0.02) of the system on its way to its new equilibrium was measured at each quench temperature. For small systematic temperature quenches just below the emulsification failure boundary (EFB) the turbidity decreases and remains constant indicating quick changes in the microstructures. Further lowering of temperature brings the system to the unstable region where the turbidity and light scattering increase sharply as function of time because of expulsion of excess oil from the microemulsion droplets. The newly formed oil-rich droplets grow in size as a function of time. These observations indicate the existence of a narrow but observable metastable region en route to the new equilibrium where both microemulsion droplets and larger oil-rich droplets coexist. The region in which microemulsion droplets are metastable is very narrow and is concentration-dependent. The presence of a metastable region is as for other similar systems attributed to the presence of a free energy barrier for the formation of the larger oil-rich droplets associated with curvature free energy of the surfactant film. The turbidity-time curves were converted to the radius-time curves using a model assuming monodisperse spherical droplets. The obtained results are in good agreement with the results for the hydrodynamic radius. The observed average radius from both type of measurements decreases in the metastable region. By performing calculation of the influence of eccentricity and size polydispersity on the observed radius, we have shown that the distribution of the microemulsion droplets becomes more homogeneous in the metastable region.

Phase behavior and kinetics of phase separation of a nonionic microemulsion of C12E5/water/1-chlorotetradecane upon a temperature quench.

The phase behavior and phase separation kinetics of a model ternary nonionic microemulsion system composed of pentaethylene glycol dodecyl ether (C12E5), water, and 1-chlorotetradecane were studied. With increasing temperature, the microemulsion exhibits the following rich phase behavior: oil-in-water phase (L1+O), droplet microemulsion phase (L1), lamellar liquid crystalline phase (Lproportional), and sponge-like (liquid) phase (L3). The microemulsion with a fixed surfactant-to-oil volume fraction ratio (Phis/Phio) of 0.81 and droplet volume fraction of 0.087 was perturbed from equilibrium by a temperature quench from the L1 region (24 degrees C) to an unstable region L1+O (13 degrees C), where the excess oil phase is in equilibrium with the microemulsion droplets. The process of phase separation in the unstable region was followed by time-resolved small-angle X-ray scattering (TR-SAXS) and time-resolved turbidity methods. Due to the large range of scattering vector (q=0.004-0.22 A(-1)) that is possible to access with the TR-SAXS method, the growth of the oil droplets and shrinking of the microemulsion droplets as a result of phase separation could be studied simultaneously. By using an advanced polydisperse ellipsoidal hard-sphere model, the experimental curves have been quantitatively analyzed. The microemulsion droplets were modeled as polydisperse core-shell ellipsoidal particles, using molecular constraints, and the oil droplets are modeled as polydisperse spheres. The radius of gyration (Rg) of the growing oil droplets, volume fraction of oil in the microemulsion droplets, and polydispersity were obtained from the fit parameters. The volume equivalent radius at the neutral plane between the surfactant head and tail of the microemulsion droplet decreased from 76 to 51 A, while the radius of oil drop increased to 217 A within the 160 min of the experiment. After about 48 min from the temperature quench, the system reaches a steady state and continues to coarsen at a constant fraction of the oil of 0.51 in the oil phase by Ostwald ripening with the power law dependence of Roil proportional, variant t1/3. The size of the oil droplets determined by the time-resolved turbidity method is in good agreement with that of the TR-SAXS, highlighting the usefulness of the method in the size determination of oil-in-water microemulsions on an absolute scale.

Phase behavior and microstructure of C12E5 nonionic microemulsions with chlorinated oils.

New non-ionic microemulsions consisting of pentaethyleneglycol dodecyl ether, water, and 1-chloroalkanes were prepared, and their phase behavior was studied. A homologous series of five different 1-chloroalkanes from 1-chlorooctane to 1-chlorohexadecane was studied. The phase behavior of the microemulsions was determined by vertical sections through the Gibbs' phase prism ("fish" plots), from which valuable information such as the microemulsion balance temperature (T(0)), efficiency of the surfactant (phi*), temperature extension of the three-body phase (DeltaT), mean temperature (T(m)), and the monomeric solubility in oil (phi(mon,oil)) was obtained. The chlorinated alkanes in the microemulsions shift the balance temperature to about 14 degrees C lower compared with their n-alkane counterparts. This indicates the polar nature of the chlorinated oils and their ability to penetrate the surfactant film. The chlorinated alkanes thus behave as short n-alkane molecules and lower the spontaneous curvature of the microemulsion droplets. The efficiency of the surfactant and the monomeric solubility in oil systematically depend on the alkyl chain length of the oil, with the efficiency and solubility decreasing with increasing alkyl chain length of 1-chloroalkane. The size and shape of the microemulsion droplets in the microemulsion phase were studied by small-angle X-ray scattering (SAXS). For a surfactant-to-oil volume fraction ratio of 0.80, the droplets can be described by ellipsoidal shapes, and the size of the droplets increased with increasing alkyl chain length.

Microemulsion droplets decorated by Brij700 block copolymer: phase behavior and structural investigation by SAXS and SANS.

The phase behavior and structure of a four-component microemulsion system forming droplets with an oil core surrounded by the non-ionic C12E5 surfactant in water and "decorated" by long PEO chains using the block copolymer/surfactant Brij 700 has been studied. The surfactant-to-oil volume ratio, the coverage density of the droplets with decorating molecules, and the temperature were varied. For a surfactant-to-oil volume ratio of 2, the solutions form isotropic and clear solutions at room temperature, and the addition of Brij molecules stabilize the micelles: the transition to an opaque phase is shifted to higher temperatures as the surface coverage increases. At a surfactant-to-oil ratio of 1, the isotropic microemulsion phase is confined to a very narrow range of temperature, which location is shifted to increasing temperature, as the amount of Brij at the surface of the droplet is increased. For large surface coverages, the lower emulsification boundary varies roughly linearly with the surface coverage. The structure of the droplet phase was investigated by small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS). For a surfactant-to-oil ratio of 2, the SANS data revealed a transition from rodlike to spherical particles when Brij molecules are added to the system, which induces a larger curvature of the surfactant film. For a surfactant-to-oil ratio of 1, the droplets are nearly spherical at all surface coverages. The intermicellar interactions effects become increasingly more pronounced as Brij is added, due to the introduction of the highly swollen corona. A quantitative analysis of some of the SAXS data was done using an advanced model based on Monte Carlo simulations. It demonstrates the strong chain-chain interactions within the corona and confirms the increased interparticle interactions, as the coverage density is increased.

Structural development of self nano emulsifying drug delivery systems (SNEDDS) during in vitro lipid digestion monitored by small-angle X-ray scattering.

PURPOSE: To investigate the structural development of the colloid phases generated during lipolysis of a lipid-based formulation in an in vitro lipolysis model, which simulates digestion in the small intestine. MATERIALS AND METHODS: Small-Angle X-Ray scattering (SAXS) coupled with the in vitro lipolysis model which accurately reproduces the solubilizing environment in the gastrointestinal tract and simulates gastrointestinal lipid digestion through the use of bile and pancreatic extracts. The combined method was used to follow the intermediate digestion products of a self nano emulsified drug delivery system (SNEDDS) under fasted conditions. SNEDDS is developed to facilitate the uptake of poorly soluble drugs. RESULTS: The data revealed that a lamellar phase forms immediately after initiation of lipolysis, whereas a hexagonal phase is formed after 60 min. The change of the relative amounts of these phases clearly demonstrates that lipolysis is a dynamic process. The formation of these phases is driven by the lipase which continuously hydrolyzes triglycerides from the oil-cores of the nanoemulsion droplets into mono- and diglycerides and fatty acids. We propose that this change of the over-all composition of the intestinal fluid with increased fraction of hydrolyzed nanoemulsion induces a change in the composition and effective critical packing parameter of the amphiphilic molecules, which determines the phase behavior of the system. Control experiments (only the digestion medium) or the surfactant (Cremophor RH 40) revealed the formation of a lamellar phase demonstrating that the hexagonal phase is due to the hydrolysis of the SNEDDS formulation. CONCLUSIONS: The current results demonstrate that SAXS measurements combined with the in vitro dynamic lipolysis model may be used to elucidate the processes encountered during the digestion of lipid-based formulations of poorly soluble drugs for oral drug delivery. Thus the combined methods may act as an efficient screening tool.