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Gels (Basel, Switzerland) Jun 2024Due to their high surface area and low weight, silica aerogels are ideally suited for several uses, including drug delivery, catalysis, and insulation. Oil-water-oil ()...
Due to their high surface area and low weight, silica aerogels are ideally suited for several uses, including drug delivery, catalysis, and insulation. Oil-water-oil () double emulsion is a simple and regulated technique for encasing a volatile oil phase in a silica shell to produce hollow silica (SiO) aerogel particles by using hydrophilic and hydrophobic emulsifiers. In this study, the oil-water-oil () double emulsion method was implemented to synthesize surface-modified hollow silica (SiO) aerogel particles in a facile and effective way. This investigation mainly focused on the influence of the N-hexane-to-water glass () ratio () in the first emulsion, silica (water glass) content concentration (), and surfactant concentration () variations. Furthermore, surface modification techniques were utilized to customize the aerogel's characteristics. The X-ray diffraction (XRD) patterns showed no imprints of impurities except SiO. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images highlight the hollow microstructure of silica particles. Zeta potential was used to determine particle size analysis of hollow silica aerogel particles. The oil-water-oil () double emulsion approach was successfully employed to synthesize surface-modified hollow silica (SiO) aerogel particles, providing precise control over the particle characteristics. By the influence of the optimization condition, this approach improves the aerogel's potential applications in drug delivery, catalysis, and insulation by enabling surface modifications.
PubMed: 38920927
DOI: 10.3390/gels10060380 -
Biomedical Materials (Bristol, England) Jun 2024Sutures are commonly used in surgical procedures and have immense potential for direct drug delivery into the wound site. However, incorporating active pharmaceutical...
Sutures are commonly used in surgical procedures and have immense potential for direct drug delivery into the wound site. However, incorporating active pharmaceutical ingredients into the sutures has always been challenging as their mechanical strength deteriorates. This study proposes a new method to produce microspheres-embedded surgical sutures that offer adequate mechanical properties for effective wound healing applications. The study used curcumin, a bioactive compound found in turmeric, as a model drug due to its anti-inflammatory, antioxidant, and anti-bacterial properties, which make it an ideal candidate for a surgical suture drug delivery system. Curcumin-loaded microspheres were produced using the emulsion solvent evaporation method with polyvinyl alcohol (PVA) as the aqueous phase. The microspheres ' particle sizes, drug loading capacity, and encapsulation efficiency were investigated. Microspheres were melt-extruded with polycaprolactone (PCL) and polyethylene glycol (PEG) via a 3D bioplotter, followed by a drawing process to optimise the mechanical strength. The sutures' thermal, physiochemical, and mechanical properties were investigated, and the drug delivery and biocompatibility were evaluated. The results showed that increasing the aqueous phase concentration resulted in smaller particle sizes and improved drug loading capacity and encapsulation efficiency. However, if PVA was used at 3% w/v or below, it prevented aggregate formation after lyophilisation, and the average particle size was found to be 34.32 ± 12.82 μm. The sutures produced with the addition of microspheres had a diameter of 0.38±0.02 mm, a smooth surface, minimal tissue drag, and proper tensile strength. Furthermore, due to the encapsulated drug-polymer structure, the sutures exhibited a prolonged and sustained drug release of up to 14 days. Microsphere-loaded sutures demonstrated non-toxicity and accelerated wound healing in the in vitro studies. We anticipate that the microsphere-loaded sutures will serve as an excellent biomedical device for facilitating wound healing.
PubMed: 38917838
DOI: 10.1088/1748-605X/ad5baa -
Drug Development and Industrial Pharmacy Jun 2024ObjectiveThe purpose of this study was to prepare and evaluate chitosan (CS) gel containing metformin (MET) loaded polycaprolactone (PCL) nanoparticles (NPs) for topical...
ObjectiveThe purpose of this study was to prepare and evaluate chitosan (CS) gel containing metformin (MET) loaded polycaprolactone (PCL) nanoparticles (NPs) for topical treatment of melanoma.SignificanceTopical administration of MET-PCL NPs-CS gel improves penetration of drug, decrease side effects and increase efficacy of treatment.MethodsMET-PCL nanoparticles were prepared by double emulsion method. Particle size, charge, encapsulation efficiency, release and morphology were evaluated. MET-PCL NPs-CS gel formulation were characterized in terms of organoleptic properties, pH, gelling time, viscosity, spreadability, release and morphology. Cytotoxicity was performed on B16F10 cells. Ex vivo permeability were done with pig skin.ResultsThe size, charge and encapsulation efficiency were found to be 180 ± 10 nm, -11.4 mV and 93%. SEM images showed that nanoparticles were spherical and smooth. An initial burst release followed by a slower release was observed. MET-PCL NPs-CS gel was found to be transparent. The pH was 4.9 ± 0.05. The gelation time was 1.6 ± 0.2 min. The viscosity results confirm pseudoplastic behaviour of gel. The spreadability by % area was 392 ± 6.4 cm. The images showed that gelling network of CS gel was composed of suspended nanoparticles. The viscosity was between 554-3503 cP. Met-PCL NPs-CS gel showed prolonged release up to 72 h. On B16F10 cells, gel showed higher cytotoxicity compared to MET solution. MET-PCL NPs-CS gel had 2-fold higher permeability in pig skin compared with Met-CS gel.ConclusionsTopical administration of Met-PCL NPs-CS gel into the skin resulted in improved dermal penetration and this promising approach may be of value in effective treatment of melanoma and other skin cancers.
PubMed: 38916971
DOI: 10.1080/03639045.2024.2372290 -
Frontiers in Medical Technology 2024Preformulation investigations into the development of drug formulations, encompassing considerations related to the structure of the drug, excipients, composition, and...
Preformulation investigations into the development of drug formulations, encompassing considerations related to the structure of the drug, excipients, composition, and physical attributes are crucial. This phase is pivotal in ensuring the ultimate success of nanoemulsion development. The objective of this study was to evaluate and define the properties of bedaquiline (BDQ) and the necessary excipients for the formulation of self-emulsifying BDQ-loaded nanoemulsions. To determine the saturation solubility of BDQ in various oils, an in-house validated HPLC method was used. Fourier transform infrared spectroscopy was utilised to identify and evaluate the compatibility between BDQ and the selected excipients. The water titration method was used to construct phase diagrams to identify the type of structure that resulted following emulsification and to characterise the behaviour of mixtures along dilution paths. The solubility studies revealed that BDQ exhibited the highest solubility in olive oil, with a solubility of 3.45 ± 0.041 mg/ml. The design space led to the formation of emulsions categorised as Winsor products. Importantly, the FTIR data indicated the absence of any potential interactions between BDQ and the chosen excipients. The preformulation studies were successful and facilitated the selection of compatible and suitable excipients for the formulation of BDQ-loaded nanoemulsions.
PubMed: 38915350
DOI: 10.3389/fmedt.2024.1388113 -
Current Pharmaceutical Biotechnology Jun 2024Self-emulsifying drug delivery systems (SEDDS) can increase the solubility and bioavailability of poorly soluble drugs. The inability of 35% to 40% of new...
Self-emulsifying drug delivery systems (SEDDS) can increase the solubility and bioavailability of poorly soluble drugs. The inability of 35% to 40% of new pharmaceuticals to dissolve in water presents a serious challenge for the pharmaceutical industry. As a result, there must be dosage proportionality, considerable intra- and inter-subject variability, poor solubility, and limited lung bioavailability. As a result, it is critical that drugs intended for oral administration be highly soluble. This can be improved through a variety of means, including salt generation and the facilitation of solid and complicated dispersion. Surfactants, lubricants, and cosolvents may occasionally be found in SEDDS or isotropic blends. Lipophilic drugs, whose absorption is limited by their dissolution rate, have been used to demonstrate the effectiveness of various formulations and techniques. These particles can form microemulsions and suitable oil-inwater emulsions with minimal agitation and dilution by the water phase as they pass through the gastrointestinal tract. This study summarises the numerous advances, biopharmaceutical components, variations, production techniques, characterisation approaches, limitations, and opportunities for SEDDS. With this context in mind, this review compiles a current account of biopharmaceutical advancements, such as the application of quality by design (QbD) methodologies to optimise drug formulations in different excipients with controllable ratios, the presence of regulatory roadblocks to progress, and the future consequences of SEDDS, encompassing composition, evaluation, diverse dosage forms, and innovative techniques for in vitro converting liquid SEDDS to solid forms.
PubMed: 38910472
DOI: 10.2174/0113892010296223240612050639 -
Journal of Controlled Release :... Jun 2024Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell...
Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled in situ loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. In vivo evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.
PubMed: 38908755
DOI: 10.1016/j.jconrel.2024.06.046 -
European Journal of Pharmaceutical... Jun 2024Lamivudine (LMD), an enantiomer of 2'-deoxy-3'-thiacytidine, plays a crucial role in combatting HIV-1 and managing hepatitis B virus infections. Despite its...
Enhancing Flowability of Lamivudine through Quasi-Emulsion Solvent-Diffusion (QESD) Crystallization: A Comprehensive Study on Surfactant Impact, Particle Morphology by QbD concepts and Tablet Compression Challenges.
Lamivudine (LMD), an enantiomer of 2'-deoxy-3'-thiacytidine, plays a crucial role in combatting HIV-1 and managing hepatitis B virus infections. Despite its effectiveness, challenges arise from its difficult flowability and tendency to agglomerate during storage, necessitating a granulation step before tablet compression, as direct compression has proven ineffective. This study aimed to optimize Lamivudine spherical agglomerates using response surface methodology, delving into the intricate relationship between design factors (concentration of tween, span, and acetone) and experimental outcomes (yield and particle size) through central composite design. Analysis of variance (ANOVA) was employed for optimization, with the Quasi-emulsion solvent-diffusion (QESD) crystallization technique utilized for the checkpoint batch. This technique, involving a single solvent and antisolvent with surfactants, showcased remarkable enhancements in flowability and reduced storage agglomeration. The impact of various surfactants [Hydroxy Propyl Methyl Cellulose (HPMC), polysorbate 80, and sorbitane monooleate] on particle morphology, flowability, and storage agglomeration during crystallization was thoroughly assessed. While achieving direct compression into tablets, the porous structure of LMD agglomerates presented challenges in tablet press production speeds, prompting adjustments such as reducing punch speed or implementing a precompression step. Positive outcomes were realized for disintegration and in vitro drug release in comparison to direct compression and wet granulation methods. In conclusion, the QESD crystallization technique successfully yielded hollow, spherical LMD agglomerates with enhanced properties, representing a significant milestone in pharmaceutical formulation.
PubMed: 38908413
DOI: 10.1016/j.ejps.2024.106835 -
International Journal of Biological... Jun 2024In this investigation, we present an innovative pH-responsive nanocomposite designed to address challenges associated with using 5-Fluorouracil (5-FU) in cancer therapy....
In this investigation, we present an innovative pH-responsive nanocomposite designed to address challenges associated with using 5-Fluorouracil (5-FU) in cancer therapy. The nanocomposite containing zein (Z), starch (S), and graphitic carbon nitride (g-CN) macromolecules is synthesized by a water-in-oil-in-water (W/O/W) double emulsion technique, serving as a carrier for 5-FU. The S/Z hydrogel matrix's entrapment and loading efficiency are greatly improved by adding g-CN nanosheets, reaching noteworthy values of 45.25 % and 86.5 %, respectively, for drug loading efficiency and entrapment efficiency. Characterization through FTIR and XRD validates the successful loading of 5-FU, elucidating the chemical bonding within the nanocomposite and crystalline characteristics. Structural analysis using FESEM, along with DLS and zeta potential measurements, reveals an average nanocomposite size of 193.48 nm, indicating a controlled structure, and a zeta potential of -42.32 mV, signifying a negatively charged surface. Studies on the in vitro release of drugs reveal that 5-FU is delivered more effectively and sustainably in acidic environments than in physiological circumstances. This highlights the fact that the created nanocarrier is pH-sensitive. Modeling release kinetics involves finding the right mathematical conditions representing underlying physicochemical processes. Employing curve-fitting techniques, predominant release mechanisms are identified, and optimal-fitting kinetic models are determined. The Baker kinetic model performed best at pH 7.4, indicating that the leading cause of the drug release was polymer swelling. In contrast, the Higuchi model was most accurate for drug release at pH 5.4, illuminating the diffusion and dissolution mechanisms involved in diffusion. To be more precise, the mechanism of release at pH 7.4 and 5.4 was anomalous transport (dissolution-controlled), according to the Korsmeyer-Peppas mathematical model. The pH-dependent swelling and degradation behavior of S/Z/g-CN@5-FU nanocomposite showed higher swelling and faster degradation in acidic environments compared to neutral conditions. Crucially, outcomes from the MTT test affirm the significant cytotoxicity of the 5-FU-loaded nanocomposite against U-87 MG brain cancer cells, while simultaneously indicating non-toxicity towards L929 fibroblast cells. These cumulative findings underscore the potential of the engineered S/Z/g-CN@5-FU as a productive and targeted therapeutic approach for cancer cells.
PubMed: 38906350
DOI: 10.1016/j.ijbiomac.2024.133275 -
European Journal of Pharmaceutics and... Jun 2024Poloxamer hydrogels are of interest as injectable depot delivery systems. However, their use for delivering hydrophobic drugs, such as curcumin, is limited due to poor...
Poloxamer hydrogels are of interest as injectable depot delivery systems. However, their use for delivering hydrophobic drugs, such as curcumin, is limited due to poor loading capacity. Here, we evaluated the influence of incorporating hydrophobic medium chain triglycerides (MCT] or amphiphilic polyethylene glycol 400 (PEG400) on the physicochemical properties, drug loading, and in-vitro compatibility of a curcumin-loaded poloxamer hydrogel. Poloxamer 407 and 188 hydrogel formulations (16:6 w/w) were prepared and MCT and PEG400 (saturated with curcumin) were added to these systems, either alone or in combination, up to 10 % w/w. Formulation viscoelasticity, gelation behaviour, injectability, morphology and release profiles were assessed. The cytocompatibility of the formulations was also assessed on dermal fibroblasts (HDFn). Both additives increased curcumin loading into the formulation. Addition of MCT to the hydrogel lowered its gelation temperature, while PEG400 had no notable impact. Both additives increased the force required to inject the formulation. PEG400 containing systems were single phase whereas MCT addition created emulsion systems. All formulations released ∼20-30 % of their loaded curcumin in sustained fashion over 24 h. The modified hydrogel systems showed great biocompatibility on cells when administering up to 100-150 µM curcumin into the culture. This study addresses a key limitation in loading hydrophobic drugs into hydrogels and provides a strategy to enhance drug loading into and performance of hydrogels by integrating additives, such as MCT and PEG400 into the systems.
PubMed: 38897552
DOI: 10.1016/j.ejpb.2024.114372 -
International Journal of Nanomedicine 2024Natural products are potential sources of anticancer components. Among various species, the lipophilic extract of the subsp. (Wiesb.) Vollm. (VALE) has shown promising...
BACKGROUND AND PURPOSE
Natural products are potential sources of anticancer components. Among various species, the lipophilic extract of the subsp. (Wiesb.) Vollm. (VALE) has shown promising therapeutic potential. The present work aimed to qualify the plant source and characterize the extract's chemical profile. In addition, a self-nanoemulsifying drug delivery system (SNEDDS) containing VALE (SNEDDS-VALE) was developed.
METHODS
subsp. histochemistry was performed, and the chemical profile of VALE was analyzed by GC-MS. After the SNEEDS-VALE development, its morphology was visualized by transmission electron microscopy (TEM), while its stability was evaluated by the average droplet size, polydispersity index (PdI) and pH. Lastly, SNEDDS-VALE chemical stability was evaluated by LC-DAD-MS.
RESULTS
The histochemical analysis showed the presence of lipophilic compounds in the leaves and stems. The major compound in the VALE was oleanolic acid, followed by lupeol acetate and ursolic acid. SNEDDS was composed of medium chain triglyceride and Kolliphor RH 40 (PEG-40 hydrogenated castor oil). A homogeneous, isotropic and stable nanoemulsion was obtained, with an average size of 36.87 ± 1.04 nm and PdI of 0.14 ± 0.02, for 14 weeks.
CONCLUSION
This is the first histochemistry analysis of subsp. growing on . which provided detailed information regarding its lipophilic compounds. A homogeneous, isotropic and stable SNEDDS-VALE was obtained to improve the low water solubility of VALE. Further, in vitro and in vivo experiments should be performed, in order to evaluate the antitumoral potential of SNEDDS-VALE.
Topics: Plant Extracts; Viscum album; Emulsions; Plant Leaves; Drug Delivery Systems; Particle Size; Nanoparticle Drug Delivery System; Nanoparticles
PubMed: 38895147
DOI: 10.2147/IJN.S464508