Ruthenium dendrimers against acute promyelocytic leukemia: in vitrostudies on HL-60 cells

2019 ◽  
Vol 11 (14) ◽  
pp. 1741-1756 ◽  
Author(s):  
Sylwia Michlewska ◽  
Maksim Ionov ◽  
Marta Maroto-Díaz ◽  
Aleksandra Szwed ◽  
Aliaksei Ihnatsyeu-Kachan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Promyelocytic Leukemia ◽  
Water Soluble ◽  
Carbosilane Dendrimers ◽  
Normal Cells ◽  
Antitumor Potential ◽  
Antitumor Properties ◽  
Ruthenium Arene

Coordination of ruthenium arene fragments on carbosilane dendrimers’ surface greatly increases their antitumor properties. Newly synthetized ruthenium dendrimers are water-soluble, monodisperse and stable. Since carbosilane dendrimers are good carriers of drugs and genes, the presence of ruthenium in their structure makes them promising candidates for new drug delivery systems with improved antitumor potential. Carbosilane ruthenium dendrimers are more toxic to cancer cells than normal cells. Results of several in vitro studies applied here indicate that carbosilane ruthenium dendrimers induce apoptosis in promyelocytic leukemia HL-60 cells.

scholarly journals Effects of Hydrophilic Carriers on Structural Transitions and In Vitro Properties of Solid Self-Microemulsifying Drug Delivery Systems

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 267 ◽  
Author(s):  
Tao Yi ◽  
Jifen Zhang
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Commercial Application ◽  
Simulated Gastric Fluid ◽  
Structural Transitions

Self-microemulsifying drug delivery systems (SMEDDS) offer potential for improving the oral bioavailability of poorly water-soluble drugs. However, their susceptibilities during long term storage and in vivo precipitation issues limit their successful commercial application. To overcome these limitations, SMEDDS can be solidified with solid carriers, thus producing solid self-microemulsifying drug delivery systems (S-SMEDDS). In this study, effects of various hydrophilic carriers on structural transitions and in vitro properties of S-SMEDDS were investigated in order to set up in vitro methods for screening out appropriate carriers for S-SMEDDS. Liquid SMEDDS was prepared and characterized using nimodipine as a model drug. The effects of various hydrophilic carriers on internal microstructure and solubilization of SMEDDS were investigated by conductivity measurement and in vitro dispersion test. The results showed that hydrophilic carriers including dextran 40, maltodextrin and PVP K30 seemed to delay the percolation transition of SMEDDS, allowing it to maintain a microstructure that was more conducive to drug dissolution, thus significantly increasing the solubilization of nimodipine in the self-microemulsifying system and decreasing drug precipitation when dispersed in simulated gastric fluid. S-SMEDDS of nimodipine were prepared by using spray drying with hydrophilic carriers. The effects of various hydrophilic carriers on in vitro properties of S-SMEDDS were investigated by using SEM, DSC, PXRD and in vitro dissolution. The results showed that properties of hydrophilic carriers, especially relative molecular mass of carriers, had obvious influences on surface morphologies of S-SMEDDS, reconstitution of microemulsion and physical state of nimodipine in S-SMEDDS. Considering that in vitro properties of S-SMEDDS are closely related to their pharmacokinetic properties in vivo, the simple and economical in vitro evaluation methods established in this paper can be used to screen solid carriers of S-SMEDDS well.

scholarly journals Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 365 ◽  
Author(s):  
Heejun Park ◽  
Eun-Sol Ha ◽  
Min-Soo Kim
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Drug Application ◽  
In Vitro Digestion ◽  
Delivery Systems ◽  
Water Soluble ◽  
Current Status ◽  
In Vitro Tests

Self-emulsifying drug delivery systems (SEDDSs) are a vital strategy to enhance the bioavailability (BA) of formulations of poorly water-soluble compounds. However, these formulations have certain limitations, including in vivo drug precipitation, poor in vitro in vivo correlation due to a lack of predictive in vitro tests, issues in handling of liquid formulation, and physico-chemical instability of drug and/or vehicle components. To overcome these limitations, which restrict the potential usage of such systems, the supersaturable SEDDSs (su-SEDDSs) have gained attention based on the fact that the inclusion of precipitation inhibitors (PIs) within SEDDSs helps maintain drug supersaturation after dispersion and digestion in the gastrointestinal tract. This improves the BA of drugs and reduces the variability of exposure. In addition, the formulation of solid su-SEDDSs has helped to overcome disadvantages of liquid or capsule dosage form. This review article discusses, in detail, the current status of su-SEDDSs that overcome the limitations of conventional SEDDSs. It discusses the definition and range of su-SEDDSs, the principle mechanisms underlying precipitation inhibition and enhanced in vivo absorption, drug application cases, biorelevance in vitro digestion models, and the development of liquid su-SEDDSs to solid dosage forms. This review also describes the effects of various physiological factors and the potential interactions between PIs and lipid, lipase or lipid digested products on the in vivo performance of su-SEDDSs. In particular, several considerations relating to the properties of PIs are discussed from various perspectives.

scholarly journals FORMULATION, DEVELOPMENT AND CHARACTERIZATION OF DRUG DELIVERY SYSTEMS BASED TELMISARTAN ENCAPSULATED IN SILK FIBROIN NANOSPHERE’S

2019 ◽  
Vol 11 (1) ◽  
pp. 247 ◽  
Author(s):  
Shahid Ud Din Wani ◽  
Gangadharappa H. V. ◽  
Ashish N. P.
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Zeta Potential ◽  
Silk Fibroin ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Random Coil ◽  
Burst Release

Objective: The aim of the present work was to formulate silk fibroin (SF) nanospheres (NS’s) for drug delivery application. The current study was designed to advance the water solubility and bio-availability of telmisartan by nanoprecipitation method.Methods: SF NS’s loaded with TS were prepared by nanoprecipitation method. The drug was dissolved in aqueous solution of SF by using acetone as a non-solvent. The prepared NS’s were then characterized by FTIR, X-ray diffraction and zeta potential, and were evaluated for its, surface morphology, %drug content, encapsulation efficiency and in vitro drug release.Results: The evaluation results of SF NS’s loaded of TS showed 74.22±0.17 % entrapment efficiency, 35.21±0.02 % of drug loading, and-4.9 mV to-13.6 mV of zeta potential due to the proper bounding of TS with the β-sheets of SF, the particle size reported was within the size range of 160-186 nm having smooth surface and were spherical in shape. The SFNS’s pattern switched from random coil to β-sheet formation on treating with acetone. FTIR and DSC studies marked no such inter-molecular interactions between SF and drug molecules. The % cumulative in vitro drug release from SF NS’s exhibited quick burst release. The in vitro cumulative drug release of SF NS’s of TS it was found that about 74% of the drug was released within 8 h and about 96% of drug released at 24 hr. The rate of drug release increased with the increase in SF ratio.Conclusion: It is believed that these SF NS’s will find potential applications in drug delivery release as drug carriers, especially poor water-soluble drugs. All these results proposed that SF NS’s are eventuality handy in various drug delivery systems.

scholarly journals Chitosan as Valuable Excipient for Oral and Topical Carvedilol Delivery Systems

2021 ◽  
Vol 14 (8) ◽  
pp. 712
Author(s):  
Szymon Sip ◽  
Magdalena Paczkowska-Walendowska ◽  
Natalia Rosiak ◽  
Andrzej Miklaszewski ◽  
Katarzyna Grabańska-Martyńska ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Gastrointestinal Tract ◽  
Drug Delivery Systems ◽  
Reference Sample ◽  
Delivery Systems ◽  
Water Soluble ◽  
Apparent Permeability ◽  
Water Soluble Drugs ◽  
Vitro Model

Chitosan is a valued excipient due to its biocompatibility properties and increasing solubility of poorly water-soluble drugs. The research presented in this paper concerns the preparation of binary combinations of chitosan (deacetylated chitin) with carvedilol (beta-blocker) to develop a formulation with a modified carvedilol release profile. As part of the research, six physical mixtures of chitosan with carvedilol were obtained and identified by spectral (PXRD, FT-IR, and Raman), thermal (DSC), and microscopic (SEM) methods. The next stage of the research estimated the profile changes and the dissolution rate for carvedilol in the obtained drug delivery systems; the reference sample was pure carvedilol. The studies were conducted at pH = 1.2 and 6.8, simulating the gastrointestinal tract conditions. Quantitative changes of carvedilol were determined using the developed isocratic UHPLC-DAD method. Established apparent permeability coefficients proved the changes in carvedilol’s permeability after introducing a drug delivery system through membranes simulating the gastrointestinal tract and skin walls. A bioadhesive potential of carvedilol–chitosan systems was confirmed using the in vitro model. The conducted research and the obtained results indicate a significant potential of using chitosan as an excipient in modern oral or epidermal drug delivery systems of carvedilol.

scholarly journals A COMPREHENSIVE REVIEW ON SUPERSATURABLE SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM

2021 ◽  
pp. 40-44
Author(s):  
MUTHADI RADHIKA REDDY ◽  
KUMAR SHIVA GUBBIYAPPA
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
In Vitro Tests ◽  
Drug Bioavailability ◽  
Advantages And Disadvantages ◽  
Anti Cancer

Lipid-based drug delivery systems are extensively reported in the literature for enhancing drug solubility, permeability, and bioavailability. Self-nanoemulsifying drug delivery systems (SNEDDS) are a superior strategy for enhancing solubility and bioavailability of poorly water-soluble compounds and the most prevailing and commercially viable oil-based approach for drugs that exhibit low dissolution rate and inadequate absorption. However, these formulations have few limitations that include in vivo drug precipitation, inferior in vitro in vivo correlation owing to unavailability of in vitro tests, handling issues of liquid formulation, and physicochemical instability of drugs. These limitations are overcome by potential systems such as supersaturable SNEDDS (S-SNEDDS) which are prepared by addition of precipitation inhibitors into formulated SNEDDS to maintain drug supersaturation post dispersion in gastrointestinal tract. These systems improve drug bioavailability and reduce the inconsistency of exposure. In addition, these formulations also help to overcome the drawbacks of liquid and capsule dosage forms. The S-SNEDDS provides an effective approach for improving the dissolution and bioavailability of anti-cancer agents. In this article, an attempt was made to present an overview of SNEDDS, S-SNEDDS, their mechanism, formulation excipients, recent advancements, advantages, and disadvantages of SNEDDS formulations. The article also focuses on reviewing the application of S-SNEDDS in enhancing the solubility and bioavailability of anti-cancer drugs in cancer therapy.

scholarly journals DESIGN AND DEVELOPMENT OF SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEMS (SMEDDS) OF TELMISARTAN FOR ENHANCEMENT OF IN VITRO DISSOLUTION AND ORAL BIOAVAILABILITY IN RABBIT

2018 ◽  
Vol 10 (4) ◽  
pp. 117 ◽  
Author(s):  
Suvendu Kumar Sahoo ◽  
Padilam Suresh ◽  
Usharani Acharya
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Zeta Potential ◽  
Droplet Size ◽  
Oral Bioavailability ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Poorly Water Soluble

Objective: The main purpose of this investigation was to prepare self-microemulsifying drug delivery system (SMEDDS) for enhancement of oral bioavailability of a poorly water soluble drug telmisartan (TLS), a BCS class II drug by improving its dissolution rate. Methods: Self-Emulsifying Drug Delivery Systems (SEDDS) of TLS were formulated using cinnamon essential oil as the oil phase, Gelucire 44/14 as the surfactant and Transcutol HP as co-surfactant. Drug-excipient interactions were studied by FTIR spectroscopy. The formulations were evaluated for its self-emulsifying ability, clarity, and stability of the aqueous dispersion after 48 h and the phase diagram was constructed to optimize the system. Selected formulations were characterized in terms of droplet size distribution, zeta potential, cloud point and were subjected to in vitro drug release studies. The bioavailability of optimized formulation was assessed in New Zealand white rabbits.Results: By considering smaller droplet size, higher zeta potential and faster rate of drug release the formulation TF9 was chosen as optimized SMEDDS formulations. TF9 was robust to different pH media and dilution volumes, remained stable after three cooling-heating cycles and after stored at 4 °C and 25 °C for 3 mo without showing a significant change in droplet size. The pharmacokinetic study in rabbits showed SMEDDS have significantly increased the Cmax and area under the curve (AUC) of TLS compared to suspension (P<0.05).Conclusion: SMEDDS can be an effective oral dosage form for enhancing aqueous solubility and improving oral bioavailability of poorly water soluble drugs.

Development of Self-Microemulsifying Drug Delivery Systems of Poorly Water-Soluble Pazopanib for Improvement of Oral Absorption

2020 ◽  
Vol 12 (1) ◽  
pp. 152-160
Author(s):  
Sung-Up Choi ◽  
Mi Jeong Kim ◽  
Sung Tae Kim ◽  
Hee-Cheol Kim ◽  
Kwan Hyung Cho ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Delivery Systems ◽  
Water Soluble ◽  
Pharmacokinetic Parameters ◽  
Poorly Water Soluble

Self-microemulsifying drug delivery systems represent a stable formulation for enhancing the solubility and absorption efficacy of poorly soluble drugs. In this study, a self-microemulsifying drug delivery system (SMEDDS) was designed and applied for oral administration of poorly water-soluble pazopanib, a Biopharmaceutical Classification Class II anticancer drug. The solubility of pazopanib was first evaluated using various oils, surfactants, and co-surfactants. Pseudoternary phase diagrams were plotted to identify the selfemulsifying region and the phase behavior of optimized vehicle selected after screening of oils, surfactants, and co-surfactants. The SMEDDS comprising Capmul MCM NF, Tween 80, and PEG 400 was fabricated for incorporating pazopanib. It exhibited spherical droplets with size of 86.9 ± 0.8 nm and zeta potential value of –14.7 ± 0.1 mV. In vitro dissolution profiles of the SMEDDS were 2.40-fold (pH 4.0) and 6.45-fold (pH 6.8) higher than that of pazopanib powder. In particular, pazopanib-SMEDDS showed pH-independent dissolution profiles. In vivo pharmacokinetic parameters of the SMEDDS revealed enhanced bioavailability of pazopanib, which was 3.32-fold higher than that of pazopanib powder when administered orally. Taken together, the SMEDDS is effective as an oral delivery vehicle for pazopanib. In addition, our findings demonstrate that self-microemulsifying drug delivery systems could be a potential tool for improving bioavailability of other poorly water-soluble drugs.

scholarly journals Advanced Static and Dynamic Fluorescence Microscopy Techniques to Investigate Drug Delivery Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 861
Author(s):  
Jacopo Cardellini ◽  
Arianna Balestri ◽  
Costanza Montis ◽  
Debora Berti
Keyword(s):  
Drug Delivery ◽  
Fluorescence Microscopy ◽  
Drug Delivery Systems ◽  
Laser Scanning ◽  
Super Resolution ◽  
Laser Scanning Confocal Microscopy ◽  
Delivery Systems ◽  
Scanning Confocal Microscopy ◽  
Biological Phenomena

In the past decade(s), fluorescence microscopy and laser scanning confocal microscopy (LSCM) have been widely employed to investigate biological and biomimetic systems for pharmaceutical applications, to determine the localization of drugs in tissues or entire organisms or the extent of their cellular uptake (in vitro). However, the diffraction limit of light, which limits the resolution to hundreds of nanometers, has for long time restricted the extent and quality of information and insight achievable through these techniques. The advent of super-resolution microscopic techniques, recognized with the 2014 Nobel prize in Chemistry, revolutionized the field thanks to the possibility to achieve nanometric resolution, i.e., the typical scale length of chemical and biological phenomena. Since then, fluorescence microscopy-related techniques have acquired renewed interest for the scientific community, both from the perspective of instrument/techniques development and from the perspective of the advanced scientific applications. In this contribution we will review the application of these techniques to the field of drug delivery, discussing how the latest advancements of static and dynamic methodologies have tremendously expanded the experimental opportunities for the characterization of drug delivery systems and for the understanding of their behaviour in biologically relevant environments.

Sign in / Sign up

Export Citation Format

Share Document