In vitro release of diclofenac diethylamine from caprylocaproyl macrogolglycerides based microemulsions

The purpose of the present study was to determine the influence of both formulation parameters and vehicle structure on in vitro release rate of amphiphilic drug diclofenac diethylamine (DDA) from microemulsion vehicles containing PEG-8 caprylic/capric glycerides (surfactant), polyglyceryl-6 dioleate (cosurfactant), isopropyl myristate and water. From the constructed pseudo-ternary phase diagram at surfactant-cosurfactant mass ratio (K(m) 1:1), the optimum oil-to-surfactant-cosurfactant mass ratio values (O/SC 0.67-1.64) for formulation of microemulsions with similar concentrations of hydrophilic, lipophilic and amphiphilic phases (balanced microemulsions) were found. The results of characterization experiments indicated bicontinuous or nonspherical water-continuous internal structure of the selected microemulsion vehicles. Low water/isopropyl myristate apparent partition coefficient for DDA as well as elevated electrical conductivity and apparent viscosity values for the investigated microemulsion formulations containing 1.16% (w/w) of DDA, suggested that the drug molecules was predominantly partitioned in the water phase and most likely selfaggregate and interact with interfacial film. Release of DDA from the selected water-continuous (W/O), oil-continuous (O/W) and balanced microemulsions was investigated using rotating paddle dissolution apparatus modified by addition of enhancer cell. A linear diffusion of DDA through regenerated cellulose membrane was observed for the W/O and O/W formulations with the low content of dispersed phase. Non-linearity of the drug release profile in the case of bicontinuous formulations was related to the more complex distribution of DDA including interactions between the drug and vehicle. The membrane flux value increases from 25.02 microgcm(-2)h(-1) (W/O microemulsion) to 117.94 microgcm(-2)h(-1) (O/W microemulsion) as the water phase concentration increases. Moreover, the obtained flux values for balanced microemulsions (29.38-63.70 microgcm(-2)h(-1)) suggested that bicontinuous microstructure hampers the release of the amphiphilic drug.     

Applications of microemulsion based drug delivery system

The use of microemulsions as drug delivery vehicle has been an exciting and attractive area of research because of its many potential and extraordinary benefits. Microemulsions offer an interesting and potentially quite powerful alternative carrier system for drug delivery because of their high solubilization capacity, transparency, thermodynamic stability, ease of preparation, and high diffusion and absorption rates when compared to solvent without the surfactant system. The oral efficacy of microemulsion has already been proved by cyclosporine formulation (Neoral), but apart from oral route, microemulsions for other routes like dermal, transdermal, ocular, vaginal, rectal, buccal, periodontal, parenteral, and nasal delivery routes have also been developed. The present review focuses on various applications of microemulsions through different above mentioned routes and also gives idea about new application of micro emulsion as oral solid dosage form, as microreactors and as blood substitute.     

Characterization of drug delivery vehicles using atomic force microscopy: current status

ABSTRACT

Introduction: The field of nanomedicine, utilizing nano-sized vehicles (nanoparticles and nanofibers) for targeted local drug delivery, has a promising future. This is dependent on the ability to analyze the chemical and physical properties of these drug carriers at the nanoscale and hence atomic force microscopy (AFM), a high-resolution imaging and local force-measurement technique, is ideally suited.

Areas covered: Following a brief introduction to the technique, the review describes how AFM has been used in selected publications from 2015 to 2018 to characterize nanoparticles and nanofibers as drug delivery vehicles. These sections are ordered into areas of increasing AFM complexity: imaging/particle sizing, surface roughness/quantitative analysis of images, and analysis of force curves (to extract nanoindentation and adhesion data).

Expert opinion: AFM imaging/sizing is used extensively for the characterization of nanoparticle and nanofiber drug delivery vehicles, with surface roughness and nanomechanical/adhesion data acquisition being less common. The field is progressing into combining AFM with other techniques, notably SEM, ToF-SIMS, Raman, Confocal, and UV. Current limitations include a 50 nm resolution limit of nanoparticles imaged within live cells and AFM tip-induced activation of cytoskeleton proteins. Following drug release real-time with AFM-spectroscopic techniques and studying drug interactions on cell receptors appear to be on the horizon.     

Imprinted polymers as drug delivery vehicles for metal-based anti-inflammatory drug

A drug delivery system based on metal-chelate imprinting is described for the first time for a metal-based drug, copper salicylate. Metal-chelate embedded polymer (MCEP) material was prepared by adding 2 equiv. of 4-vinyl pyridine, 8 equiv. of 2-hydroxyethyl methacrylate, 32 equiv. of ethyleneglycoldimethacrylate to 1 equiv. of copper salicylate in 10 ml of 2-methoxyethanol and then polymerizing thermally in the presence of 2,2'-azobisisobutyronitrile as initiator. The removal of the embedded copper salicylate from MCEP to prepare metal-chelate imprinted polymer (MCIP) was assessed by X-ray photoelectron spectroscopy (XPS), flame atomic absorption spectroscopy (FAAS) and high performance liquid chromatography (HPLC) techniques. Conventional or non-imprinted polymer material was prepared in a similar manner to MCEP, but without the addition of copper salicylate to the synthesis recipe. The drug release behaviour was examined in vitro with polymer materials having different template to monomer ratio, different crosslinker density and with polymer material loaded with copper salicylate to different extent. Detailed drug release studies with the drug loaded to MCIP and NIP materials unequivocally establish the higher and sustained release of the therapeutic agent over several days in addition to higher drug loading capacity with the former material.     

Using microemulsion formulations for oral drug delivery of therapeutic peptides

Peptide drugs are increasingly becoming a very important class of therapeutic agents with the rapid advances in the field of biotechnology engineering. However, these drugs are generally not suitable for oral administration. In this review, the main physico-chemical and biopharmaceutical characteristics of peptides are summarized. The obstacles to peptide drug absorption and the different possibilities for solving these difficulties are listed. Results using this formulation approach for oral drug delivery of peptides are apparently promising with some specific peptides such as cyclosporin. Various mechanisms are only beginning to be understood and further investigations need to be performed in this area to explain the results obtained with some peptides.     

Perfluorocarbon compounds as vehicles for pulmonary drug delivery

Drug delivery to the diseased lung is hindered by the buildup of fluid and shunting of blood flow away from the site of injury. The use of perfluorocarbon compounds (PFCs) as drug delivery vehicles has been proposed to overcome these obstacles. This drug delivery approach is based on the unique properties of PFCs. For example, PFCs can homogeneously fill the lung and recruit airways by replacing edematous fluid. Analogously, drugs administered with a PFC vehicle are expected to be homogeneously distributed throughout the lung. At the same time, intrapulmonary administration of the drug will achieve higher drug concentrations in the lung than conventional approaches, while reducing systemic exposure. Unfortunately, PFCs are poor solvents for typical drug molecules. To overcome this obstacle, several approaches, such as dispersions, prodrugs, solubilizing agents and (micro)emulsions, are under investigation to develop homogeneous PFC–drug mixtures suitable for intrapulmonary administration.     

Perfluorocarbon compounds as vehicles for pulmonary drug delivery

Drug delivery to the diseased lung is hindered by the buildup of fluid and shunting of blood flow away from the site of injury. The use of perfluorocarbon compounds (PFCs) as drug delivery vehicles has been proposed to overcome these obstacles. This drug delivery approach is based on the unique properties of PFCs. For example, PFCs can homogeneously fill the lung and recruit airways by replacing edematous fluid. Analogously, drugs administered with a PFC vehicle are expected to be homogeneously distributed throughout the lung. At the same time, intrapulmonary administration of the drug will achieve higher drug concentrations in the lung than conventional approaches, while reducing systemic exposure. Unfortunately, PFCs are poor solvents for typical drug molecules. To overcome this obstacle, several approaches, such as dispersions, prodrugs, solubilizing agents and (micro)emulsions, are under investigation to develop homogeneous PFC-drug mixtures suitable for intrapulmonary administration.     

葛根素微乳的制备

目的:制备葛根素微乳口服给药系统(PUE-ME).方法:通过溶解度实验、处方配伍实验和伪三元相图的绘制,以乳化时间、色泽为指标,筛选油相、表面活性剂、助表面活性剂的最佳搭配和处方配比.结果:葛根素在微乳中的溶解度最高可达77.11 mg/mL.结论:所制备的PUE-ME对葛根素增溶效果显著,将为PUE的口服制剂的进一步开发提供依据.     

Auto-associative amphiphilic polysaccharides as drug delivery systems

Self-assembly of amphiphilic polysaccharides provides a positive outlook for drug delivery systems without the need for solvents or surfactants. Various polymeric amphiphilic polysaccharides undergo intramolecular or intermolecular associations in water. This type of association, promoted by hydrophobic segments, led to the formation of various drug delivery systems such as micelles, nanoparticles, liposomes and hydrogels. Here, we review a selection of the most important amphiphilic polysaccharides used as drug delivery systems and their pharmaceutical applications. Attention focuses on amphiphilic chitosan owing to its unique properties such as excellent biocompatibility, non-toxicity and antimicrobial and bioadhesive properties.     

Nanodisks: hydrophobic drug delivery vehicles

Members of the class of exchangeable apolipoproteins possess the unique capacity to transform phospholipid vesicle substrates into nanoscale disk-shaped bilayers. This reaction can proceed in the presence of exogenous hydrophobic biomolecules, resulting in the formation of novel transport vehicles termed nanodisks (NDs). The objective of this study is to describe the structural organization of NDs and evaluate the utility of these complexes as hydrophobic biomolecule transport vehicles. The topics presented focus on two distinct water insoluble drugs, amphotericin B (AMB) and all trans retinoic acid (ATRA). In vitro and in vivo studies reveal that AMB-ND display potent anti-fungal and anti-protozoal activity, while ATRA-ND show promise in the treatment of cancer. The versatility conferred by the presence of a polypeptide component provides opportunities for targeted delivery of ND to cells.     

Designing and testing of an effective oil-in-water microemulsion drug delivery system for in vivo application

The phase behavior of a new psedoternary system of clove oil/Tween 20 has been studied. Several compositions from the single-phase region were selected and their stability toward time, temperature, and electrolytes has been examined. A particular composition(clove oil/Tween 20/water as 5/30/65) was chosen as the drug delivery system from the clear oil-in-water zone of the pseudoternary system. The droplet dimension and the polydispersity state of the particular composition was determined by dynamic light scattering. A bioactive compound quarcetin was encapsulated in the vehicle. The efficacy of the drug in the vehicle was examined against leishmaniasis in hamster models. The hepatotoxicity of the vehicle (o/w microemulsion) with and without the drug quarcetin was examined by estimating serum alkaline phosphatase, glutamate pyruvate transaminase, urea, and creatinine.     

PLGA microparticles: possible vehicles for topical drug delivery

Distribution of PLGA-microparticles in porcine skin, after its topical application, was studied in vitro using microparticles containing rhodamine as a fluorescent probe. PLGA-microparticles loaded with rhodamine were prepared using a solvent evaporation technique. Skin distribution of fluorescent microparticles was performed, by horizontal and vertical slicing of frozen skin. Fluorescence photomicrographs revealed that PLGA-microparticles could penetrate through the stratum corneum and reach the epidermis. However, permeation experiments showed that these microparticles were not able to reach the receptor compartment of the diffusion cells, even in a period of 24 h. The carriers described in this work could be used as vehicles for topical drug delivery, in order to obtain a sustained drug release into the skin, improving therapy by reduction of time intervals between doses.     

Nanodiamonds as vehicles for systemic and localized drug delivery

Owing to their exceptional biocompatibility and unique surface properties, nanodiamonds (NDs) are shown to be a progressively promising nanomaterial for drug delivery. In this article, NDs as a platform for a host of biomedical applications are described, with an emphasis on cancer therapy, ranging from systemic modalities to primary constituents within polymer hybrid microfilms. Experimental results and theoretical explanations of ND–drug dynamics are compared. Water-dispersion of previously insoluble therapeutics when complexed with NDs demonstrates great promise in expanding current drug delivery options. Various forms of incorporating NDs within microfilms as a localized drug release coating and implant are also discussed.     

Chitosan and its derivatives as vehicles for drug delivery

Abstract

Chitosan and its derivatives as vehicles for drug delivery can achieve the purpose of sustained release and controlled release for drugs, improve the stability of drugs, and reduce adverse drug reactions. So, the bioavailability of drugs can be enhanced. Therefore, chitosan and its derivatives have become a hotspot in the field of drug delivery. Their characteristics as drug delivery vectors were introduced, the types and applications were summarized. The development direction of chitosan and its derivatives in this field was also forecasted.     

Cholesterol-bile salt vesicles as potential delivery vehicles for drug and vaccine delivery

The aim of this study was to further investigate the interactions between cholesterol (CH) and mixed bile salts (BS) (sodium cholate and sodium deoxycholate) and their suitability for drug and vaccine delivery. Insulin was used as a model protein to assess the ability of CH:BS vesicles to entrap a therapeutically relevant macromolecule. The association of protein (FITC-insulin) with the CH:BS structure was confirmed with fluorescence microscopy, and the overall morphology of the vesicles was examined with atomic force microscopy (AFM). Results demonstrate that the nature of the vesicles formed between CH and BS is dependent not only on the concentration of BS but also on the increasing CH concentration leading to CH crystal formation.     

Molecular imprinted polymers as drug delivery vehicles

This review is aimed to discuss the molecular imprinted polymer (MIP)-based drug delivery systems (DDS). Molecular imprinted polymers have proved to possess the potential and also as a suitable material in several areas over a long period of time. However, only recently it has been employed for pharmaceuticals and biomedical applications, particularly as drug delivery vehicles due to properties including selective recognition generated from imprinting the desired analyte, favorable in harsh experimental conditions, and feedback-controlled recognitive drug release. Hence, this review will discuss their synthesis, the reason they are selected as drug delivery vehicles and for their applications in several drug administration routes (i.e. transdermal, ocular and gastrointestinal or stimuli-reactive routes).     

Fluorocarbon nanoparticles as multifunctional drug delivery vehicles

The history and current status of fluorocarbon nanoparticles in biomedicine is briefly reviewed. The deficiencies of current fluorocarbon nanoparticle formulations are highlighted. Strategies to remedy such deficiencies and to functionalize fluorocarbon nanoparticles are presented. Potential applications of fluorocarbon nanoparticles as multifunctional drug delivery vehicles are discussed. The strength of fluorocarbon nanoparticles as drug delivery vehicles is that they integrate drug delivery with non-invasive MR imaging so that the biodistribution of the pharmaceutical entity (drug+delivery vehicle) can be monitored in real time. This, in turn, permits the physician to adjust treatment plan for each patient based on his/her actual response to the ongoing treatment.     

Fluorocarbon nanoparticles as multifunctional drug delivery vehicles

The history and current status of fluorocarbon nanoparticles in biomedicine is briefly reviewed. The deficiencies of current fluorocarbon nanoparticle formulations are highlighted. Strategies to remedy such deficiencies and to functionalize fluorocarbon nanoparticles are presented. Potential applications of fluorocarbon nanoparticles as multifunctional drug delivery vehicles are discussed. The strength of fluorocarbon nanoparticles as drug delivery vehicles is that they integrate drug delivery with non-invasive MR imaging so that the biodistribution of the pharmaceutical entity (drug + delivery vehicle) can be monitored in real time. This, in turn, permits the physician to adjust treatment plan for each patient based on his/her actual response to the ongoing treatment.     

Normal flora: living vehicles for non-invasive protein drug delivery

Feasibility to use probiotic bacteria as a living protein delivery system through oral route was assessed in vitro. Lactococcus lactis transformed with a plasmid to express and secret beta-lactamase was used to deliver beta-lactamase through Caco-2 monolayer, an intestine epithelium. Transport of beta-lactamase through Caco-2 monolayer was carried out in the transwells. The viability and integrity of the cell monolayers co-cultured with L. lactis was examined by trypan blue exclusion method and by measuring the transport of mannitol and propranolol as well as the transepithelial electrical resistance (TEER). Results show that it is feasible to use cell culture technique to evaluate the drug delivery by normal flora. The transport rate of beta-lactamase when delivered by L. lactis was 2.0 +/- 0.1 x 10(-2)h(-1) (n = 9) and through free solution form was 1.0 +/- 0.1 x 10(-2)h-1. When co-cultured with L. lactis, Caco-2 cell viability decreased to 98, 96, and 94% at 6, 8, and 10h, respectively. Transport of mannitol through Caco-2 cell monolayer was significantly increased and the transport of propranolol through Caco-2 cell monolayer was significantly decreased in the presence of L. lactis. Increase in the amount of protein delivered is probably due to the concentrate of the protein by L. lactis on the monolayer (absorption surface) and the opening of the tight junction of Caco-2 monolayer by L. lactis.     

Block copolymeric biotransport carriers as versatile vehicles for drug delivery

This review describes block co-polymer-based systems that are used in drug delivery. The main focus is on amphiphilic block co-polymers, the application of which modifies the pharmacological performance of various classes of drugs and is attracting more and more attention. The two main reasons for this are the high tendency of block co-polymer-based drug formulations to self-assemble and the flexibility of block co-polymer chemistry, which allows precise tailoring of the carrier to virtually any chemical entity. The combination of these and some other features makes it possible to adjust block co-polymer-based drug formulations to achieve the most beneficial balance in their biological interactions (biotransport), with systems that control drug removal from the body and those that are responsible for drug therapeutic activity. The following major aspects are considered: