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Open accessJournal ArticleDOI: 10.3390/PH14030212

D-α-Tocopherol-Based Micelles for Successful Encapsulation of Retinoic Acid.

04 Mar 2021-Pharmaceuticals, policy and law (Multidisciplinary Digital Publishing Institute)-Vol. 14, Iss: 3, pp 212
Abstract: All-trans-retinoic acid (ATRA) represents the first-choice treatment for several skin diseases, including epithelial skin cancer and acne. However, ATRA’s cutaneous side effects, like redness and peeling, and its high instability limit its efficacy. To address these drawbacks and to improve ATRA solubilization, we prepared ATRA-loaded micelles (ATRA-TPGSs), by its encapsulation in D-α-tocopheryl-polyethylene-glycol-succinate (TPGS). First, to explore the feasibility of the project, a solubility study based on the equilibrium method was performed; then, six ATRA-TPGS formulations were prepared by the solvent-casting method using different TPGS amounts. ATRA-TPGSs showed small sizes (11–20 nm), low polydispersity, slightly negative zeta potential, and proved good encapsulation efficiency, confirmed by a chemometric-assisted Fourier transform infrared spectroscopy (FTIR) investigation. ATRA-TPGS stability was also investigated to choose the most stable formulation. Using Carbopol® 980 as gelling agent, ATRA-TPGS-loaded gels were obtained and analyzed for their rheological profiles. Ex vivo release studies from ATRA-TPGSs were performed by Franz cells, demonstrating a permeation after 24 h of 22 ± 4 µ cm−2. ATRA-TPGSs showed enhanced cytotoxic effects on melanoma cells, suggesting that these formulations may represent a valid alternative to improve patient compliance and to achieve more efficacious therapeutic outcomes.

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7 results found

Open accessJournal ArticleDOI: 10.3390/PHARMACEUTICS13081128
23 Jul 2021-Pharmaceutics
Abstract: Children affected by chronic liver disease exhibit impaired neurocognitive development and growth due to the low absorption and digestion of nutrients. Furthermore, malnutrition is an adverse prognostic factor in liver transplantation as it is associated with an increase in morbidity and mortality. D-α-tocopheryl-polyethylene-glycol-succinate (TPGS) is currently administered per os as a vitamin E source to improve children’s survival and well-being; however, TPGS alone does not reverse spinocerebellar degeneration and lipid peroxidation. To potentiate the effects of TPGS, we loaded micelles with resveratrol (RES), a natural polyphenol, with antioxidant and antiinflammatory activities, which has demonstrated protective action in the liver. Firstly, we investigated the suitability of TPGS to encapsulate RES in micelles by means of a phase-solubility study, then RES-TPGS formulations were prepared via solvent casting and solvent diffusion evaporation methods. RES-TPGS colloidal dispersions showed small mean diameters (12 nm), low polydispersity, and quite neutral Zeta potentials. The formulations showed a sustained drug release and a good drug loading capacity, further confirmed by infrared spectroscopy and differential scanning calorimetry. RES-TPGSs exhibited unaltered antioxidant activity compared to pristine RES via the DPPH assay and a significant reduction in toxicity compared to empty TPGS on HaCaT cells. Thus, RES-TPGS micelles may overcome the challenges of current liver disease therapy by providing more protective effects thanks to the antioxidant activity of RES and by reducing the surfactant toxicity on normal cells.

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3 Citations

Open accessJournal ArticleDOI: 10.3390/NANO11092196
26 Aug 2021-Nanomaterials
Abstract: Ursolic acid (UA) is a pentacyclic triterpenoid found in many medicinal plants and aromas endowed with numerous in vitro pharmacological activities, including antibacterial effects. Unfortunately, UA is poorly administered in vivo, due to its water insolubility, low bioavailability, and residual systemic toxicity, thus making urgent the development of water-soluble UA formulations. Dendrimers are nonpareil macromolecules possessing highly controlled size, shape, and architecture. In dendrimers with cationic surface, the contemporary presence of inner cavities and of hydrophilic peripheral functions, allows to encapsulate hydrophobic non-water-soluble drugs as UA, to enhance their water-solubility and stability, and to promote their protracted release, thus decreasing their systemic toxicity. In this paper, aiming at developing a new UA-based antibacterial agent administrable in vivo, we reported the physical entrapment of UA in a biodegradable not cytotoxic cationic dendrimer (G4K). UA-loaded dendrimer nanoparticles (UA-G4K) were obtained, which showed a drug loading (DL%) much higher than those previously reported, a protracted release profile governed by diffusion mechanisms, and no cytotoxicity. Also, UA-G4K was characterized by principal components analysis (PCA)-processed FTIR spectroscopy, by NMR and elemental analyses, and by dynamic light scattering experiments (DLS). The water solubility of UA-G4K was found to be 1868-fold times higher than that of pristine UA, thus making its clinical application feasible.

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Topics: Antibacterial agent (55%), Dendrimer (54%)

2 Citations

Open accessJournal ArticleDOI: 10.3390/APP112211022
21 Nov 2021-Applied Sciences
Abstract: Electrospun polycaprolactone nanofibers with embedded magnetic nanoparticles were developed for use in the topical delivery of antipsoriatic drugs. To test a hydrophobic drug, a tazarotene has been used, which is an efficient retinoid derivative. Such a smart hyperthermia nanofiber system with self-generated heat from the incorporated magnetic nanoparticles induced drug release in response to on–off switching of alternating magnetic fields for the delivery of tazarotene through the skin, as quantified using Franz cells. This highly efficient external field-controllable system with minimal skin irritation could create a new avenue for the topical therapy of psoriasis.

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Topics: Tazarotene (60%), Controlled release (50%)

Open accessJournal ArticleDOI: 10.3390/NANO11102662
10 Oct 2021-Nanomaterials
Abstract: 2-(4-Bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4) was synthetized and successfully evaluated concerning numerous biological activities, except for antimicrobial and cytotoxic effects. Due to the antimicrobial effects possessed by pyrazole nucleus, which have been widely reported, and the worldwide need for new antimicrobial agents, we thought it would be interesting to test BBB4 and to evaluate its possible antibacterial effects. Nevertheless, since it is water-insoluble, the future clinical application of BBB4 will remain utopic unless water-soluble BBB4 formulations are developed. To this end, before implementing biological evaluations, BBB4 was herein re-synthetized and characterized, and a new water-soluble BBB4-based nano-formulation was developed by its physical entrapment in a biodegradable non-cytotoxic cationic dendrimer (G4K), without recovering harmful solvents as DMSO or surfactants. The obtained BBB4 nanoparticles (BBB4-G4K NPs) showed good drug loading (DL%), satisfying encapsulation efficiency (EE%), and a biphasic quantitative release profile governed by first-order kinetics after 24 h. Additionally, BBB4-G4K was characterized by ATR-FTIR spectroscopy, NMR, SEM, dynamic light scattering analysis (DLS), and potentiometric titration experiments. While, before the nanotechnological manipulation, BBB4 was completely water-insoluble, in the form of BBB4-G4K NPs, its water-solubility resulted in being 105-fold higher than that of the pristine form, thus establishing the feasibility of its clinical application.

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Topics: Dendrimer (52%), Pyrazole (52%)

Open accessJournal ArticleDOI: 10.3390/PHARMACEUTICS13111976
21 Nov 2021-Pharmaceutics
Abstract: Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and systemic toxicity limit the possibilities of its application in vivo. Consequently, the beneficial activities of UA observed in vitro lose their potential clinical relevance unless water-soluble, not cytotoxic UA formulations are developed. With a nano-technologic approach, we have recently prepared water-soluble UA-loaded dendrimer nanoparticles (UA-G4K NPs) non-cytotoxic on HeLa cells, with promising physicochemical properties for their clinical applications. In this work, with the aim of developing a new antibacterial agent based on UA, UA-G4K has been tested on different strains of the Enterococcus genus, including marine isolates, toward which UA-G4K has shown minimum inhibitory concentrations (MICs) very low (0.5–4.3 µM), regardless of their resistance to antibiotics. Time-kill experiments, in addition to confirming the previously reported bactericidal activity of UA against E. faecium, also established it for UA-G4K. Furthermore, cytotoxicity experiments on human keratinocytes revealed that nanomanipulation of UA significantly reduced the cytotoxicity of UA, providing UA-G4K NPs with very high LD50 (96.4 µM) and selectivity indices, which were in the range 22.4–192.8, depending on the enterococcal strain tested. Due to its physicochemical and biological properties, UA-G4K could be seriously evaluated as a novel oral-administrable therapeutic option for tackling difficult-to-treat enterococcal infections.

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Topics: Antibacterial agent (55%), Ursolic acid (53%)


58 results found

Journal ArticleDOI: 10.1016/J.EJPS.2013.02.006
Yuanyuan Guo1, Jun Luo2, Songwei Tan1, Ben Oketch Otieno1  +1 moreInstitutions (2)
Abstract: D-α-Tocopheryl polyethylene glycol 1000 succinate (simply TPGS or Vitamin E TPGS) is formed by the esterification of Vitamin E succinate with polyethylene glycol 1000. As novel nonionic surfactant, it exhibits amphipathic properties and can form stable micelles in aqueous vehicles at concentration as low as 0.02 wt%. It has been widely investigated for its emulsifying, dispersing, gelling, and solubilizing effects on poorly water-soluble drugs. It can also act as a P-glycoprotein (P-gp) inhibitor and has been served as an excipient for overcoming multidrug resistance (MDR) and for increasing the oral bioavailability of many anticancer drugs. Since TPGS has been approved by FDA as a safe pharmaceutic adjuvant, many TPGS-based drug delivery systems (DDS) have been developed. In this review, we discuss TPGS properties as a P-gp inhibitor, solubilizer/absorption and permeation enhancer in drug delivery and TPGS-related formulations such as nanocrystals, nanosuspensions, tablets/solid dispersions, adjuvant in vaccine systems, nutrition supplement, plasticizer of film, anticancer reagent and so on. This review will greatly impact and bring out new insights in the use of TPGS in DDS.

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Topics: Drug delivery (52%)

377 Citations

Journal ArticleDOI: 10.1016/J.JCONREL.2004.11.020
Chiara Sinico1, Maria Manconi1, Marcello Peppi1, Francesco Lai1  +2 moreInstitutions (1)
Abstract: The influence of liposome composition, size, lamellarity and charge on the (trans)dermal delivery of tretinoin (TRA) was studied. For this purpose we studied both multilamellar (MLV) or unilamellar (UV) liposomes. Positively or negatively charged liposomes were obtained using either hydrogenated (Phospholipon®90H) or non-hydrogenated soy phosphatidylcholine (Phospholipon®90) and cholesterol, in combination with stearylamine or dicetylphosphate. Liposomal formulations were characterized by transmission electron microscopy (TEM) and optical and light polarized microscopy for vesicle formation and morphology, and by dynamic laser light scattering for size distribution. In order to obtain more information about the stability and the thermodynamic activity of the liposomal tretinoin, TRA diffusion through a lipophilic membrane was investigated. The effect of the vesicular incorporation of tretinoin on its accumulation into the newborn pig skin was also studied. The experiments were performed in vitro using Franz cells in occlusive conditions and were compared to three different controls. The tretinoin amount delivered through and accumulated in the several skin layers was detected by HPLC. Furthermore, TEM in combination with osmium tetroxide was used to visualize the skin structure after the liposomal administration. Overall obtained results showed that liposomes may be an interesting carrier for tretinoin in skin disease treatment, when appropriate formulations are used. In particular, negatively charged liposomes strongly improved newborn pig skin hydration and TRA retention, though no evidence of intact vesicle penetration was found.

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Topics: Liposome (56%), Vesicle (51%)

251 Citations

Journal ArticleDOI: 10.1023/A:1016015113795
D. Giron1Institutions (1)
Abstract: Thermal analysis methods are well-established techniques in research laboratories of pharmaceutical industry. The robustness and sensitivity of instrumentation, the introduction of automation and of reliable software according to the industrial needs widened considerably the areas of applications inthe last decade. Calibration of instruments and validation of results follow the state of the art of cGMP as for other analytical techniques. Thermal analysis techniques are especially useful for the study of the behavior of the poly-phasic systems drug substances and excipients and find a unique place for new delivery systems. Since change of temperature and moisture occur by processing and storage, changes of the solid state may have a considerable effect on activity, toxicity and stability of compounds. Current requirements of the International Conference of Harmonisation for the characterization and the quantitation of polymorphism in new entities re-enforce the position of thermal analysis techniques. This challenging task needs the use of complementary methods. Combined techniques and microcalorimetry demonstrate their advantages. This article reviews the current use of thermal analysis and combined techniques in research and development and in production. The advantage of commercially coupled techniques to thermogravimetry is emphasized with some examples.

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224 Citations

Journal ArticleDOI: 10.1016/J.IJPHARM.2006.02.018
Abstract: Mixed micelles prepared of poly(ethylene glycol)2000-phosphatidyl ethanolamine conjugate (PEG(2000)-PE) and d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in 1:1 molar ratio have been investigated. Micelle formation was confirmed by NMR spectroscopy. CMC of the micelles was found to be 1.5 x 10(-5)M. Poorly soluble anti-cancer drug paclitaxel (PCL) was efficiently solubilized in 15 nm non-toxic PEG-PE/TPGS micelles. PCL entrapment was quite stable with only about 20% of the incorporated drug released from micelles after 48 h at 37 degrees C. In addition, PCL-containing PEG(2000)-PE/TPGS micelles were stable in vitro under various conditions modeling the physiological ones, in particular, at low pH values and in the presence of bile acids, which is especially important for their possible oral administration. Fluorescently labeled micelles demonstrated time-dependent internalization by human colon adenocarcinoma cell line, Caco-2. The internalization of PEG(2000)-PE/TPGS micelles loaded with P-glycoprotein (P-gp) substrate, rhodamine-123 (RH-123), opposite to the internalization of the free RH-123, was not influenced by the inhibition of the P-gp pump with verapamil hydrochloride, which assumes a P-gp-independent micelle internalization.

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Topics: Micelle (57%), Polyethylene glycol (55%), PEG ratio (54%) ... read more

182 Citations

Open accessJournal ArticleDOI: 10.7150/THNO.22711
Conglian Yang1, Tingting Wu1, Yan Qi1, Zhiping Zhang1Institutions (1)
01 Jan 2018-Theranostics
Abstract: D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future.

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Topics: Drug delivery (54%)

179 Citations