Model Hydrophobic Drug Research Articles

Sulconazole-Loaded Solid Lipid Nanoparticles for Enhanced Antifungal Activity: In Vitro and In Vivo Approach.

Solid lipid nanoparticles (SLNs) have the advantages of a cell-specific delivery and sustained release of hydrophobic drugs that can be exploited against infectious diseases. The topical delivery of hydrophobic drugs needs pharmaceutical strategies to enhance drug permeation, which is a challenge faced by conventional formulations containing a drug suspended in gel, creams or ointments. We report the fabrication and optimization of SLNs with sulconazole (SCZ) as a model hydrophobic drug and then a formulation of an SLN-based topical gel against fungal infections. The SLNs were optimized through excipients of glyceryl monostearate and Phospholipon® 90 H as lipids and tween 20 as a surfactant for its size, drug entrapment and sustained release and resistance against aggregation. The SCZ-SLNs were physically characterized for their particle size (89.81 ± 2.64), polydispersity index (0.311 ± 0.07), zeta potential (-26.98 ± 1.19) and encapsulation efficiency (86.52 ± 0.53). The SCZ-SLNs showed sustained release of 85.29% drug at the 12 h timepoint. The TEM results demonstrated spherical morphology, while DSC, XRD and FTIR showed the compatibility of the drug inside SLNs. SCZ-SLNs were incorporated into a gel using carbopol and were further optimized for their rheological behavior, pH, homogeneity and spreadability on the skin. The antifungal activity against Candida albicans and Trichophyton rubrum was increased in comparison to a SCZ carbopol-based gel. In vivo antifungal activity in rabbits presented faster healing of skin fungal infections. The histopathological examination of the treated skin from rabbits presented restoration of the dermal architecture. In summary, the approach of formulating SLNs into a topical gel presented an advantageous drug delivery system against mycosis.

Hybrid Poly(β-amino ester) Triblock Copolymers Utilizing a RAFT Polymerization Grafting-From Methodology.

The biocompatibility, biodegradability, and responsiveness of poly(β-amino esters) (PBAEs) has led to their widespread use as biomaterials for drug and gene delivery. Nonetheless, the step-growth polymerization mechanism that yields PBAEs limits the scope for their structural optimization toward specific applications because of limited monomer choice and end-group modifications. Moreover, to date the post-synthetic functionalization of PBAEs has relied on grafting-to approaches, challenged by the need for efficient polymer-polymer coupling and potentially difficult post-conjugation purification. Here a novel grafting-from approach to grow reversible addition-fragmentation chain transfer (RAFT) polymers from a PBAE scaffold is described. This is achieved through PBAE conversion into a macromolecular chain transfer agent through a multistep capping procedure, followed by RAFT polymerization with a range of monomers to produce PBAE-RAFT hybrid triblock copolymers. Following successful synthesis, the potential biological applications of these ABA triblock copolymers are illustrated through assembly into polymeric micelles and encapsulation of a model hydrophobic drug, followed by successful nanoparticle (NP) uptake in breast cancer cells. The findings demonstrate this novel synthetic methodology can expand the scope of PBAEs as biomaterials.

Multi-hierarchical nanoparticles with tunable core by emulsion polymerization processes

Nanoparticles (NPs) with functional cores are gaining research interest due to their advanced architecture. However, exposed reactive groups on NP surfaces can lead to material side reactions and biomedical tissue damage. NPs with multi-hierarchical morphologies can be synthesized by various methods; however, controlling the size and position of the functional groups using conventional and scalable methods is still a challenge. This study explores emulsion-based polymerization methods for producing multi-hierarchical NPs with varying sizes and compositions. We compared micro-, macro-, and semi-batch emulsion polymerization using 2-hydroxyethyl methacrylate (HEMA) and pentafluorophenyl methacrylate (PFMA) as co-monomers. The components present in PFMA can be substituted and are used for post-synthetic functionalization. The results suggest that the architecture of the synthesized NPs is multi-hierarchical, with the substitutable pentafluorophenyl units surrounded by HEMA monomers. Additionally, we evaluated the NPs' ability to enhance dermal drug penetration using nile red as a hydrophobic drug model. Significant variations in skin permeation enhancement properties were observed among the NPs, underscoring the impact of the synthesis method on nanocarriers' drug delivery performance.

Injectable On-Demand Pulsatile Drug Delivery Hydrogels Using Alternating Magnetic Field-Triggered Polymer Glass Transitions.

Remote-controlled pulsatile or staged release has significant potential in a wide range of therapeutic treatments. However, most current approaches are hindered by the low resolution between the on- and off-states of drug release and the need for surgical implantation of larger controlled-release devices. Herein, we describe a method that addresses these limitations by combining injectable hydrogels, superparamagnetic iron oxide nanoparticles (SPIONs) that heat when exposed to an alternating magnetic field (AMF), and polymeric nanoparticles with a glass transition temperature (Tg) just above physiological temperature. Miniemulsion polymerization was used to fabricate poly(methyl methacrylate-co-butyl methacrylate) (p(MMA-co-BMA)) nanoparticles loaded with a model hydrophobic drug and tuned to have a Tg value just above physiological temperature (∼43 °C). Co-encapsulation of these drug-loaded nanoparticles with SPIONs inside a carbohydrate-based injectable hydrogel matrix (formed by rapid hydrazone cross-linking chemistry) enables injection and immobilization of the nanoparticles at the target site. Temperature cycling facilitated a 2.5:1 to 6:1 on/off rhodamine release ratio when the nanocomposites were switched between 37 and 45 °C; release was similarly enhanced by exposing the nanocomposite hydrogel to an AMF to drive heating, with enhanced release upon pulsing observed even 1 week after injection. Coupled with the apparent cytocompatibility of all of the nanocomposite components, these injectable nanocomposite hydrogels are promising as minimally invasive but remotely actuated release delivery vehicles capable of complex release kinetics with high on-off resolution.

MOF-Thermogel Composites for Differentiated and Sustained Dual Drug Delivery.

In recent years, multidrug therapy has gained increasing popularity due to the possibility of achieving synergistic drug action and sequential delivery of different medical payloads for enhanced treatment efficacy. While a number of composite material release platforms have been developed, few combine the bottom-up design versatility of metal-organic frameworks (MOFs) to tailor drug release behavior, with the convenience of temperature-responsive hydrogels (or thermogels) in their unique ease of administration and formulation. Yet, despite their potential, MOF-thermogel composites have been largely overlooked for simultaneous multidrug delivery. Herein, we report the first systematic study of common MOFs (UiO-66, MIL-53(Al), MIL-100(Fe), and MOF-808) with different pore sizes, geometries, and hydrophobicities for their ability to achieve simultaneous dual drug release when embedded within PEG-containing thermogel matrices. After establishing that MOFs exert small influences on the rheological properties of the thermogels despite the penetration of polymers into the MOF pores in solution, the release profiles of ibuprofen and caffeine as model hydrophobic and hydrophilic drugs, respectively, from MOF-thermogel composites were investigated. Through these studies, we elucidated the important role of hydrophobic matching between MOF pores and loaded drugs in order for the MOF component to distinctly influence drug release kinetics. These findings enabled us to identify a viable MOF-thermogel composite containing UiO-66 that showed vastly different release kinetics between ibuprofen and caffeine, enabling temporally differentiated yet sustained simultaneous drug release to be achieved. Finally, the MOF-thermogel composites were shown to be noncytotoxic in vitro, paving the way for these underexploited composite materials to find possible clinical applications for multidrug therapy.

Fabrication of PEG-PLGA Microparticles with Tunable Sizes for Controlled Drug Release Application.

Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Although existing techniques for producing polymeric drug carriers offer the possibility of achieving greater production yield across a wide range of sizes, these methods are improbable to precisely tune particle size while upholding uniformity of particle size and morphology, ensuring consistent production yield, maintaining batch-to-batch reproducibility, and improving drug loading capacity. Herein, we developed a novel scalable method for the synthesis of tunable-sized microparticles with improved monodispersity and batch-to-batch reproducibility via the coaxial flow-phase separation technique. The study evaluated the effect of various process parameters on microparticle size and polydispersity, including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution, whereas surfactant concentration had the most substantial impact on the morphology of particles. In addition to synthesizing microparticles of spherical morphology yielding particle sizes in the range of 5-50 µm across different formulations, we were able to also synthesize several microparticles exhibiting different morphologies and particle concentrations as a demonstration of the tunability and scalability of this method. Notably, by adjusting key determining process parameters, it was possible to achieve microparticle sizes in a comparable range (5-7 µm) for different formulations despite varying the concentration of polymer and volume of polymer solution in the organic phase by an order of magnitude. Finally, by the incorporation of fluorescent dyes as model hydrophilic and hydrophobic drugs, we further demonstrated how polymer amount influences drug loading capacity, encapsulation efficiency, and release kinetics of these microparticles of comparable sizes. Our study provides a framework for fabricating both hydrophobic and hydrophilic drug-loaded microparticles and elucidates the interplay between fabrication parameters and the physicochemical properties of microparticles, thereby offering an itinerary for expanding the applicability of this method for producing polymeric microparticles with desirable characteristics for specific drug delivery applications.

Efficient Synthesis of Submicrometer‐Sized Active Pharmaceuticals by Laser Fragmentation in a Liquid‐Jet Passage Reactor with Minimum Degradation

AbstractOne challenge in the development of new drug formulations is overcoming their low solubility in relevant aqueous media. Reducing the particle size of drug powders to a few hundred nanometers is a well‐known method that leads to an increase in solubility due to an elevated total surface area. However, state‐of‐the‐art comminution techniques like cryo‐milling suffer from degradation and contamination of the drugs, particularly when sub‐micrometer diameters are aspired that require long processing times. In this work, picosecond‐pulsed laser fragmentation in liquids (LFL) of dispersed drug particles in a liquid‐jet passage reactor is used as a wear‐free comminution technique using the hydrophobic oral model drugs naproxen, prednisolone, ketoconazole, and megestrol acetate. Particle size and morphology of the drug particles are characterized using scanning electron microscopy (SEM) and changes in particle size distributions upon irradiation are quantified using an analytical centrifuge. The findings highlight the superior fragmentation efficiency of the liquid‐jet passage reactor setup, with a 100 times higher fraction of submicrometer particles (SMP) of the drugs compared to the batch control, which enhances solubility and goes along with minimal chemical degradation (<1%), determined by attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR), high‐performance liquid chromatography (HPLC), and X‐ray diffraction (XRD). Moreover, the underlying predominantly photo‐mechanically induced laser fragmentation mechanisms of organic microparticles (MP) are discussed.

Development of Gelled-Oil Nanoparticles for the Encapsulation and Release of Berberine.

In this study, a new drug carrier based on gelled-oil nanoparticles (GNPs) was designed and synthesized for the encapsulation and release of the model hydrophobic drug, berberine chloride (BCl). Two compositions with different oil phases were examined, sesame oil (SO) and cinnamaldehyde (Cin), which were emulsified with water, stabilized with Tween 80 (Tw80), and gelled using an N-alkylated primary oxalamide low-molecular-weight gelator (LMWG) to give stable dispersions of GNPs between 100 and 200 nm in size. The GNP formulation with Cin was significantly favored over SO due to (1) lower gel melting temperatures, (2) higher gel mechanical strength, and (3) significantly higher solubility, encapsulation efficiency, and loading of BCl. Also, the solubility and loading of BCl in Cin were significantly increased (at least 7-fold) with the addition of cinnamic acid. In vitro release studies showed that the release of BCl from the GNPs was independent of gelator concentration and lower than that for BCl solution and the corresponding nanoemulsion (no LWMG). Also, cell internalization studies suggested that the N-alkylated primary oxalamide LMWG did not interfere with the internalization efficiency of BCl into mouse mast cells. Altogether, this work demonstrates the potential use of these new GNP formulations for biomedical studies involving the encapsulation of drugs and nutraceuticals and their controlled release.

Effect of hydrophilic polymers on the solubility and dissolution enhancement of rivaroxaban/beta-cyclodextrin inclusion complexes

BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of β-cyclodextrin (βCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with βCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with βCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: βCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% w/w to optimized binary formulation RIV:βCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: βCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban.

Tuning stimuli-responsive properties of alginate hydrogels through layer-by-layer functionalization for dual-responsive dual drug release

This study aimed to understand the effect of layer-by-layer (LbL) modification on the stimuli-responsive properties of physical alginate (ALG) hydrogels and examine the potential of LbL-coated hydrogels as dual responsive, dual drug releasing platforms for antibacterial applications. ALG hydrogels were functionalized through LbL self-assembly using temperature-responsive poly(2-isopropyl-2-oxazoline) (PiPOX) and pH-responsive tannic acid (TA). Ciprofloxacin (CIP) and Curcumin (CUR) were used as model hydrophilic and hydrophobic drugs, respectively. CIP was included in the hydrogel during LbL process, whereas CUR was incorporated into the hydrogel through gelation in the presence of CUR-loaded CaCO3 microparticles. The effect of LbL modification on the stimuli-responsive swelling, stability and drug release properties of hydrogels was examined in comparison with bare hydrogels. We have shown that LbL modification resulted in a partial loss of solid content from the hydrogel, leading to a greater swelling. In addition, LbL modification imparted temperature-responsiveness to ALG hydrogel and provided enhanced CIP release upon increasing the temperature at pH 7.4. On the other hand, LbL-coated hydrogels displayed minimal CIP release at pH 5.5 regardless of the temperature. The antibacterial activity of LbL-coated hydrogels was greater at pH 7.4 than pH 5.5 against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. The combination of CIP and CUR provided enhanced antibacterial effect on the inhibition of E.coli growth at both pH 7.4 and pH 5.5. This effect became more remarkable as the CIP concentration was decreased at a constant CUR concentration in the hydrogels. However, the combinatorial effect of CIP and CUR was not observed with S. aureus. Overall, these results may be promising for wound healing applications where drug release is triggered when the pH becomes alkaline in the presence of bacterial colonization.

Structure Property Relationship of Micellar Waterborne Poly(Urethane-Urea): Tunable Mechanical Properties and Controlled Release Profiles with Amphiphilic Triblock Copolymers.

Waterborne polyurethane (WPU) has attracted significant interest as a promising alternative to solvent-based polyurethane (SPU) due to its positive impact on safety and sustainability. However, significant limitations of WPU, such as its weaker mechanical strength, limit its ability to replace SPU. Triblock amphiphilic diols are promising materials to enhance the performance of WPU due to their well-defined hydrophobic-hydrophilic structures. Yet, our understanding of the relationship between the hydrophobic-hydrophilic arrangements of triblock amphiphilic diols and the physical properties of WPU remains limited. In this study, we show that by controlling the micellar structure of WPU in aqueous solution via the introduction of triblock amphiphilic diols, the postcuring efficiency and the resulting mechanical strength of WPU can be significantly enhanced. Small-angle neutron scattering confirmed the microstructure and spatial distribution of hydrophilic and hydrophobic segments in the engineered WPU micelles. In addition, we show that the control of the WPU micellar structure through triblock amphiphilic diols renders WPU attractive in the applications of controlled release, such as drug delivery. Here, curcumin was used as a model hydrophobic drug, and the drug release behavior from WPU-micellar-based drug delivery systems was characterized. It was found that curcumin-loaded WPU drug delivery systems were highly biocompatible and exhibited antibacterial properties in vitro. Furthermore, the sustained release profile of the drug was found to be dependent on the structure of the triblock amphiphilic diols, suggesting the possibility of controlling the drug release profile via the selection of triblock amphiphilic diols. This work shows that by shedding light on the structure-property relationship of triblock amphiphilic diol-containing WPU micelles, we may enhance the applicability of WPU systems and move closer to realizing their promising potential in real-life applications.

Cholesterol included self-assembled electrospun proliposomes as a feasible approach for drug delivery

Liposomes are the most well established systems for drug delivery due to their biocompatibility, extended circulation time and availability of surface modification. Besides, there are limitations mainly related with their inadequate stability. Electrospinning is a versatile method which incorporates many drugs into polymeric nanofibers. Self-assembly liposomes obtained from nanofibers could be an advantageous approach that can overcome the stability problems of liposomes. In this study, proliposome nanofibers of soy phosphatidylcholine(PC) and PC/Cholesterol(Chol) were developed in dry state using polyvinylpyrrolidone(PVP), by a single step method, electrospinning. Hydrocortisone(HC) was used as a hydrophobic model drug. All formulations were successfully electrospun according to SEM images. DSC, FT-IR and XRD studies showed that the drug was encapsulated and transformed into an amorphous form. The hydration of PC/Chol containing nanofibers provides to form liposomes around 150 nm with −30mV zeta potential and 0.23 polydispersity index. Self-assembled liposomes obtained by hydration of nanofibers and PDI values were found to be very low without extrusion or sonication step. No vesicular structure was observed for PVP nanofibers without PC. The release studies showed the addition of Chol to nanofiber structure, enhanced HC release within 48 h. Additionally, three-months stability data showed that Chol improves in vitro stability of liposomes.

Surface Eroding Methacrylic Anhydride Copolymers and Model Drug Release

AbstractMethacrylic anhydride (MAA)‐based copolymers are synthesized to probe how comonomer composition and type affect the erosion profiles. Anhydrides readily undergo hydrolysis, which when combined with high crosslink density and hydrophobicity tend to exhibit an ideal surface erosion mechanism for drug delivery, tissue adhesives, and biocement applications. The cylindrical (10 mm diameter × 5 mm height) polyanhydrides are degraded under pseudo‐physiological conditions and surface erosion is qualitatively observed via photographs. The non‐anhydride comonomer can be utilized to tune erosion profiles while retaining degradability and product solubility. The comonomer can accelerate or slow the degradation process to a greater extent at low MAA concentrations. Drug release is conducted using purpurin to model hydrophobic drugs. Purpurin concentration is quantified using UV–visible spectral analysis. Purpurin extends the degradation profile due to a combination of local pH changes, hydrophobicity, and molecular diffusion. Linear purpurin release is observed as a function of polymer erosion (0.9897 R2) thus confirming a surface erosion‐mediated drug release mechanism.

Performance of alkyl β-D-maltosides in molecular self-assembly and formation of oil-in-water nanoemulsions as drug delivery systems

Alkyl β-D-maltosides are nonionic sugar-based surfactants that can be used as excipients in lipid-based nanoparticles because of their physiological functions and biocompatibility. The self-assembly of alkyl β-D-maltosides (C8-C12) was studied to investigate the effects of alkyl chain length in the binary and ternary systems. Surface tension measurements in the binary systems revealed a synergistic effect on the stability of mixed surfactants with Tween 80 (T80) in the critical aggregation concentration (CAC). Subsequently, formulations of 10:90 wt% oil-in-water (O/W) nanoemulsions (ternary systems) containing T80/alkyl β-D-maltosides with and without cyclosporine (CsA) as the hydrophobic model drug were characterised by particle size, polydispersity index (PDI), morphology, rheology, and physical stability. The formulations of all nanoemulsion systems were found to be stable against phase separation for 28 days at room temperature. The hydrophobic effect of n-dodecyl-β-D-maltoside (DDM, C12) was stronger by enhancing the stability of T80 nanoemulsion in molecular self-assembly compared to the shorter chains of the maltosides. The in vitro drug release study showed that T80/DDM nanoemulsion improved the cumulative release of CsA in 24 h by 98.33 ± 7.72% compared to T80 nanoemulsion at 83.75 ± 4.05%. The release of CsA has the highest fit with the Korsmeyer-Peppas kinetic model (R2 > 0.9), suggesting that CsA is released slowly from the oily core of nanoemulsions to the dissolution medium due to its hydrophobic nature. The cytotoxicity study against 3T3 cells showed that all formulations had no cytotoxicity effect (IC50) up to 500 μg/mL. The findings demonstrated that T80/DDM nanoemulsion holds great promise as a drug delivery system for the treatment of psoriasis.

Ultra-small micelles together with UTMD enhanced the therapeutic effect of docetaxel on Glioblastoma

Owing to the difficult-to-penetrate blood-brain barrier (BBB), glioblastoma (GBM) doesn't respond well to the current chemical therapeutics. In this study, ultra-small micelles (NMs) self-assembled by RRR-a-tocopheryl succinate-grafted-ε-polylysine conjugate (VES-g-ε-PLL) as the delivery vehicle of chemical therapeutics in conjunction with ultrasound-targeted microbubble destruction (UTMD) to surmount BBB and treat GBM. Docetaxel (DTX) as a hydrophobic model drug was incorporated into NMs. DTX-loaded micelles (DTX-NMs) with 3.08% of drug loading exhibited a hydrodynamic diameter (33.2 nm) and positive Zeta potential (16.9 mV), having a remarkable tumor-permeating capacity. Furthermore, DTX-NMs presented good stability in physiologic condition. The sustained- release profile of DTX-NMs was also displayed by dynamic dialysis. Treatment of DTX-NMs together with UTMD led to more pronounced apoptosis of C6 tumor cells than DTX-NMs alone. Moreover, compared with the DTX solution or DTX-NMs alone, the combination of DTX-NMs with UTMD had a stronger inhibitory effect on tumor growth for GBM-bearing rats. The median survival period of GBM-bearing rats was extended to 75 days in the DTX-NMs+UTMD group from under 25 days in the control group. The invasive growth of glioblastoma was largely inhibited by the combination of DTX-NMs with UTMD, which was demonstrated by staining of Ki67, caspase-3, and CD31, together with TUNEL assay. In conclusion, the combination of ultra-small micelles (NMs) with UTMD may be a promising strategy to overcome the limitations of the first-line chemotherapeutics against GBM.

Poly(ε-caprolactone)-poly(ethylene glycol) Tri-Block Copolymer as Quercetin Delivery System for Human Colorectal Carcinoma Cells: Synthesis, Characterization and In Vitro Study.

Quercetin is a hydrophobic molecule with short blood circulation times and instability. The development of a nano-delivery system formulation of quercetin may increase its bioavailability, resulting in greater tumor suppressing effects. Triblock ABA type polycaprolactone-polyethylenglycol- polycaprolactone (PCL-PEG-PCL) copolymers have been synthetized using ring-opening polymerization of caprolactone from PEG diol. The copolymers were characterized by nuclear magnetic resonance (NMR), diffusion-ordered NMR spectroscopy (DOSY), and gel permeation chromatography (GPC). The triblock copolymers self-assembled in water forming micelles consisting of a core of biodegradable polycaprolactone (PCL) and a corona of polyethylenglycol (PEG). The core-shell PCL-PEG-PCL nanoparticles were able to incorporate quercetin into the core. They were characterized by dynamic light scattering (DLS) and NMR. The cellular uptake efficiency of human colorectal carcinoma cells was quantitatively determined by flow cytometry using nanoparticles loaded with Nile Red as hydrophobic model drug. The cytotoxic effect of quercetin-loaded nanoparticles was evaluated on HCT 116 cells, showing promising results.

Hydrogen sulfide detection induced burst release of model drug from polymeric micelles

In this study, a poly(ester-amide)-based amphiphilic polymer (named P1) is prepared for the burst release of a model drug, rhodamine, from polymeric micelles, triggered by hydrogen sulfide (H2S) detection. P1 was synthesized by the Passerini multicomponent polymerization of a hydrophobic H2S-specific unit (M1) with 6-isocyanohexanoic acid, and hydrophilic polyethylene glycol (PEG) dicarboxylic acid. When P1 self-assembles in water, it generates polymeric micelles consisting of a hydrophilic PEG shell and a hydrophobic core derived from M1 with 6-isocyanohexanoic acid. P1 micelles exhibited selective colorimetric (colorless to yellow) and fluorometric (non-emissive to blue emission) H2S detection in water. The limit of detection was as low as 0.09 mM. Upon the exposure of H2S to a P1 micelle solution encapsulating the hydrophobic model drug, rhodamine, H2S detection induced a sequential and self-destructive elimination process of the polymer backbone, resulting in the swelling of the micelles and the abrupt release of rhodamine.

O/W Pickering emulsion stabilized by magnesium carbonate particles for drug delivery systems

This study investigates the formulation of surfactant-free Pickering emulsions that release a drug at a specific pH to improve its oral bioavailability. The stabilizing particles composed of magnesium carbonate particles. Pickering oil-in-water emulsions stabilized with magnesium carbonate particles and encapsulating a hydrophobic drug model (ibuprofen) were formulated using a high-energy process with rotor-stator turbo mixer (IKA® T25 digital ultra-Turrax). The experimental approach explored the impact of all formulation parameters, dispersed phase and amount of magnesium carbonate particles on the physicochemical properties of Pickering emulsions. The O/W Pickering emulsion was characterized by a methylene blue test, pH and conductivity measurements, and droplet size determination. In addition, Pickering emulsions stabilized by magnesium carbonate particles have the advantage of being destabilized in acidic medium leading to the release of the active principle via the droplets. The acidic medium release study (pH equal to 1.2) showed ibuprofen release as a function of initial droplet loading and saturation concentration. In the simulated intestinal medium at pH equal to 6.8, we found a better release of ibuprofen from emulsions that already had saturation in an acid medium. Thus, the interest of these Pickering emulsions lies on the fact that their non-toxicity and magnesium carbonate particles allow destabilization of the emulsions and release of the drug. These emulsions not only protect patients from the side effects of acid-based drugs, but also contribute to increase the bioavailability of these acidic drugs.
 Keywords: emulsion -Pickering-magnesium carbonate- ibuprofen-oral bioavailability

The impact of solvent selection on the characteristics of niosome nanoparticles prepared by microfluidic mixing

The aim of this work was to assess the impact of solvent selection on the characteristics of niosomes prepared by microfluidic mixing. To achieve this, niosomes were manufactured using bench-scale microfluidic mixing systems by changing the type of aqueous and/or organic solvents used to prepare the particles. Niosomes were prepared using different non-ionic surfactants and cholesterol compositions with different solvents and evaluated to investigate the influence of organic and aqueous solvents on the particle's physiochemical characteristics. Here we demonstrated that the solvent selection is a key factor to be considered during the preparation of niosomes with microfluidic mixing. The type of organic solvent was shown to significantly affect the size and the size distribution of the prepared particles. In general, niosome size increased with increasing organic solvent polarity, without affecting the niosomes stability. Moreover, changing the aqueous solvent used to hydrate the lipid components significantly (p < 0.05) affected the characteristics of the prepared niosomes in terms of particles size, size distribution, and surface charge. This impact of solvent selection on the final product is dependent on the lipid components where niosomes prepared with different compositions will have different characteristics when changing the type of organic and/or aqueous solvents. The apparent encapsulation efficiency of quinine as a model hydrophobic drug was subsequently shown to be significantly (p < 0.05) affected by the type of the organic solvent used to prepare the niosomes, while the impact of the organic solvent had less impact on the apparent encapsulation of atenolol as a model hydrophilic drug.

Dermaplaning for Transdermal Drug Permeation Enhancement: A Qualitative and Quantitative Assessment.

In this study, we sought to investigate the effect of dermaplaning, a popular cosmeceutical skin rejuvenation technique on the permeation of drugs. Baclofen and diclofenac were used as hydrophilic and hydrophobic model drugs, respectively. A specific area of skin was treated with 4 strokes of a dermaplane device. Interindividual variability was assessed by having multiple users operate the device for the study. Dermaplaned skin was histologically evaluated and characterized for resistance drop and the depletion of the stratum corneum (SC). The effect of dermaplaning on drug permeation was investigated via in vitro permeation studies. Histology studies depicted the removal of SC and some parts of viable epidermis by dermaplaning. A significant drop in electrical resistance post skin dermaplaning was observed for all treatment groups, signifying the depletion of barrier properties of SC (p < 0.05). Consequently, significant drug flux and permeation were observed over 24h for the model drugs across dermaplaned skin. However, varied absorption profile was observed in vitro for both drugs across dermaplaned skin. Dermaplaning displayed a better suitability for significantly enhancing the permeation of the hydrophilic drug, baclofen. Evidence of variation in results post dermaplaning was observed amidst multiple users as well (p < 0.05).