-
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 -
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 -
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 -
Molecules (Basel, Switzerland) Jun 2024Oleoresin of Roxb. ex G. Don (DA) has been traditionally used for local medicinal applications. Several in vitro studies have indicated its pharmacological potential....
Oleoresin of Roxb. ex G. Don (DA) has been traditionally used for local medicinal applications. Several in vitro studies have indicated its pharmacological potential. However, the low water solubility hinders its use and development for pharmaceutical purposes. The study aimed to (1) formulate oil-in-water (/) Pickering emulsions of DA oleoresin and (2) demonstrate its activities in cancer cells. The Pickering emulsions were formulated using biocompatible carboxylated cellulose nanocrystal (cCNC) as an emulsifier. The optimized emulsion comprised 3% (F1) and 4% (/) (F2) of oleoresin in 1% cCNC and 0.1 M NaCl, which possessed homogeneity and physical stability compared with other formulations with uniform droplet size and low viscosity. The constituent analysis indicated the presence of the biomarker dipterocarpol in both F1 and F2. The pharmacological effects of the two emulsions were demonstrated in vitro against two cancer cell lines, HepG2 and HCT116. Both F1 and F2 suppressed cancer cell viability. The treated cells underwent apoptosis, as demonstrated by distinct nuclear morphological changes in DAPI-stained cells and Annexin V/PI-stained cells detected by flow cytometry. Our study highlights the prospect of Pickering emulsions for oleoresin, emphasizing enhanced stability and potential pharmacological advantages.
Topics: Humans; Hep G2 Cells; Cell Proliferation; Emulsions; HCT116 Cells; Apoptosis; Plant Extracts; Colonic Neoplasms; Cell Survival; Liver Neoplasms; Antineoplastic Agents, Phytogenic
PubMed: 38893569
DOI: 10.3390/molecules29112695 -
Molecules (Basel, Switzerland) May 2024Epigallocatechin gallate (EGCG), the principal catechin in green tea, exhibits diverse therapeutic properties. However, its clinical efficacy is hindered by poor...
Epigallocatechin gallate (EGCG), the principal catechin in green tea, exhibits diverse therapeutic properties. However, its clinical efficacy is hindered by poor stability and low bioavailability. This study investigated solid particle-in-oil-in-water (S/O/W) emulsions stabilized by whey protein isolate (WPI) and sodium caseinate (NaCas) as carriers to enhance the bioavailability and intestinal absorption of EGCG. Molecular docking revealed binding interactions between EGCG and these macromolecules. The WPI- and NaCas-stabilized emulsions exhibited high encapsulation efficiencies (>80%) and significantly enhanced the bioaccessibility of EGCG by 64% compared to free EGCG after simulated gastrointestinal digestion. Notably, the NaCas emulsion facilitated higher intestinal permeability of EGCG across Caco-2 monolayers, attributed to the strong intermolecular interactions between caseins and EGCG. Furthermore, the emulsions protected Caco-2 cells against oxidative stress by suppressing intracellular reactive oxygen species generation. These findings demonstrate the potential of WPI- and NaCas-stabilized emulsions as effective delivery systems to improve the bioavailability, stability, and bioactivity of polyphenols like EGCG, enabling their applications in functional foods and nutraceuticals.
Topics: Catechin; Humans; Whey Proteins; Caseins; Caco-2 Cells; Biological Availability; Emulsions; Molecular Docking Simulation; Reactive Oxygen Species; Oxidative Stress; Drug Carriers; Antioxidants; Intestinal Absorption
PubMed: 38893466
DOI: 10.3390/molecules29112588 -
Molecules (Basel, Switzerland) May 2024An increased demand for natural products nowadays most specifically probiotics (PROs) is evident since it comes in conjunction with beneficial health effects for... (Review)
Review
An increased demand for natural products nowadays most specifically probiotics (PROs) is evident since it comes in conjunction with beneficial health effects for consumers. In this regard, it is well known that encapsulation could positively affect the PROs' viability throughout food manufacturing and long-term storage. This paper aims to analyze and review various double/multilayer strategies for encapsulation of PROs. Double-layer encapsulation of PROs by electrohydrodynamic atomization or electrospraying technology has been reported along with layer-by-layer assembly and water-in-oil-in-water (W/O/W) double emulsions to produce multilayer PROs-loaded carriers. Finally, their applications in food products are presented. The resistance and viability of loaded PROs to mechanical damage, during gastrointestinal transit and shelf life of these trapping systems, are also described. The PROs encapsulation in double- and multiple-layer coatings combined with other technologies can be examined to increase the opportunities for new functional products with amended functionalities opening a novel horizon in food technology.
Topics: Probiotics; Emulsions; Humans; Drug Carriers; Drug Compounding; Food Technology
PubMed: 38893306
DOI: 10.3390/molecules29112431 -
International Journal of Molecular... May 2024Oil-core nanocapsules (NCs, also known as nanoemulsions) are of great interest due to their application as efficient carriers of various lipophilic bioactives, such as...
Oil-core nanocapsules (NCs, also known as nanoemulsions) are of great interest due to their application as efficient carriers of various lipophilic bioactives, such as drugs. Here, we reported for the first time the preparation and characterization of NCs consisting of chondroitin sulfate (CS)-based shells and liquid oil cores. For this purpose, two amphiphilic CS derivatives (AmCSs) were obtained by grafting the polysaccharide chain with octadecyl or oleyl groups. AmCS-based NCs were prepared by an ultrasound-assisted emulsification of an oil phase consisting of a mixture of triglyceride oil and vitamin E in a dispersion of AmCSs. Dynamic light scattering and cryo-transmission electron microscopy showed that the as-prepared core-shell NCs have typical diameters in the range of 30-250 nm and spherical morphology. Since CS is a strong polyanion, these particles have a very low surface potential, which promotes their stabilization. The cytotoxicity of the CS derivatives and CS-based NCs and their impact on cell proliferation were analyzed using human keratinocytes (HaCaTs) and primary human skin fibroblasts (HSFs). In vitro studies showed that AmCSs dispersed in an aqueous medium, exhibiting mild cytotoxicity against HaCaTs, while for HSFs, the harmful effect was observed only for the CS derivative with octadecyl side groups. However, the nanocapsules coated with AmCSs, especially those filled with vitamin E, show high biocompatibility with human skin cells. Due to their stability under physiological conditions, the high encapsulation efficiency of their hydrophobic compounds, and biocompatibility, AmCS-based NCs are promising carriers for the topical delivery of lipophilic bioactive compounds.
Topics: Nanocapsules; Humans; Chondroitin Sulfates; Drug Carriers; Dietary Supplements; Fibroblasts; Cell Proliferation; Keratinocytes; Emulsions; Particle Size; Vitamin E; Cell Survival; Cell Line; HaCaT Cells
PubMed: 38892083
DOI: 10.3390/ijms25115897 -
BMC Complementary Medicine and Therapies Jun 2024The present study aimed to assess the anti-leishmanial effects of curcumin nanoemulsion (CUR-NE) against Leishmania major (MRHO/IR/75/ER) in both in vitro and in vivo...
The present study aimed to assess the anti-leishmanial effects of curcumin nanoemulsion (CUR-NE) against Leishmania major (MRHO/IR/75/ER) in both in vitro and in vivo experiments. CUR-NE was successfully prepared via the spontaneous emulsification method. The in vitro effect of various concentrations of CUR-NE against L. major promastigotes was assessed using the flow cytometry method. In vivo experiments were carried out in BALB/c mice inoculated subcutaneously with 2 × 10L. major promastigotes. Mice were treated with topical CUR-NE (2.5 mg/ml), intra-lesion injection of CUR-NE (2.5 mg/ml), topical CUR suspension (CUR-S, 2.5 mg/ml), topical NE without CUR (NE-no CUR), amphotericin B as the positive control group, and infected untreated mice as the negative control group. In vitro exposure of promastigotes to CUR-NE showed a dose-dependent anti-leishmanial effect, with a 67.52 ± 0.35% mortality rate at a concentration of 1250 µg/ml and an IC50 of 643.56 µg/ml. In vivo experiments showed that topical CUR-NE and CUR-S significantly decreased the mean lesion size in mice after four weeks from 4.73 ± 1.28 to 2.78 ± 1.28 mm and 4.45 ± 0.88 to 3.23 ± 0.59 mm, respectively (p = 0.001). Furthermore, CUR-NE significantly decreased the parasite load in treated mice compared with the negative control group (p = 0.001). Results from the current study demonstrated the promising activity of CUR-NE against L. major in both in vitro and in vivo experiments. Moreover, CUR-NE was more efficient than CUR-S in healing and reducing parasite burden in mouse models. Future studies should aim to identify molecular mechanisms as well as the pharmacologic and pharmacokinetic aspects of CUR-NE.
Topics: Animals; Curcumin; Mice, Inbred BALB C; Leishmania major; Mice; Emulsions; Leishmaniasis, Cutaneous; Antiprotozoal Agents; Female; Nanoparticles
PubMed: 38890586
DOI: 10.1186/s12906-024-04522-1 -
Preparation of Luvangetin Nanoemulsions: Antimicrobial Mechanism and Role in Infected Wound Healing.International Journal of Nanomedicine 2024Incorporation of luvangetin in nanoemulsions for antimicrobial and therapeutic use in infected wound healing.
PURPOSE
Incorporation of luvangetin in nanoemulsions for antimicrobial and therapeutic use in infected wound healing.
PATIENTS AND METHODS
Luvangetin nanoemulsions were prepared by high-speed shear method and characterized based on their appearance structure, average droplet size, polydispersity index (PDI), electric potential, storage stability. Optimized formulation of luvangetin nanoemulsion by Box-Behnken design (BBD). The antimicrobial activity and antimicrobial mechanism of luvangetin nanoemulsions against common hospital pathogens, ie, and , were investigated using luvangetin nanoemulsions. The biosafety of luvangetin nanoemulsion was evaluated through cytotoxicity, apoptosis, and reactive oxygen species (ROS) assay experiments using human normal epidermal cells and endothelial cells. Finally, the effect of luvangetin nanoemulsion on healing of infected wounds was investigated in B6 mice.
RESULTS
Luvangetin nanoemulsion formulation consists of 2.5% sunflower seed oil, 10% emulsifier Span-20 and 7 minutes of shear time, and with good stability. Luvangetin nanoemulsion produces antibacterial activity against and by disrupting the structure of bacterial cell membranes. Luvangetin nanoemulsion are biologically safe for HaCat and HUVEC. Luvangetin nanoemulsion showed good therapeutic effect on MRSA infected wounds in mice.
CONCLUSION
For the first time, developed a new formulation called luvangetin nanoemulsion, which exhibited superior antibacterial effects against Gram-positive bacteria. Luvangetin nanoemulsion has a favorable effect in promoting infected wound healing. We have combined luvangetin, which has multiple activities, with nanoemulsions to provide a new topical fungicidal formulation, and have comprehensively evaluated its effectiveness and safety, opening up new possibilities for further applications of luvangetin.
Topics: Animals; Wound Healing; Escherichia coli; Humans; Emulsions; Staphylococcus aureus; Mice; Anti-Bacterial Agents; Wound Infection; Nanoparticles; Reactive Oxygen Species; Mice, Inbred C57BL; Staphylococcal Infections; Cell Line; Microbial Sensitivity Tests
PubMed: 38882542
DOI: 10.2147/IJN.S457322