Colloidal Drug Carrier Systems Research Articles

Modern topical drugs-new developments in galenics and pharmacology

The importance of topically applied pharmaceuticals, especially for the treatment of dermatological diseases, is still essential. Thanks to detailed knowledge of the organisation and function of the physicochemical barrier of the skin, new galenic concepts have increasingly been developed to market maturity in recent years. Colloidal drug carrier systems in particular, but also targeted physicochemical modifications of matrices are used to optimise the cutaneous bioavailability of topically applied drugs. In addition, new molecules are increasingly becoming available for the development of these preparations or drugs known from systemic therapy are being formulated into topicals. Against this background, dermatopharmacology is also developing more and more into ahighly specialised science in this area, which is producing innovative concepts for the therapy of special indications. In addition to the classic small-molecule drugs, biotechnological molecules are increasingly finding their way into application, so that amodern age of dermatopharmacology has dawned, which will open up previously unimagined possibilities for topical therapy now and in the coming years.

A review on the functions, preparation and future aspects of nanocapsules

The nano technology in medicinal field offers many exciting possibilities. Many techniques are being usedtoday. The application of many nanoparticles were developing and these involve the utilization of manufactured nanocapsules to form repairs at cellular level and it’s sometimes refers as nano medicine. Nanocapsules are submicroscopic colloidal drug carrier systems composed of an oily or an aqueous core surrounded by a thin polymer membrane. Two technologies can be used to obtain such nanocapsules: the interfacial polymerization of a monomer or the interfacial nanodeposition of a preformed polymer. In future the nanotechnology can creat many wonders in medical field. Nanotechnology is wonderfull technology that can used in diagnosis and treatment in medical field. This review was aimed to knowing the preparation, new aspects, and the applications of the nanocapsules.

Screening of Electrolyte Complexes Formed Between Dextran Sulfate and Amine Structures of Small-Molecule Drugs.

Formation of an electrolyte complex using the electrostatic interactions between a polyanionic polymer and a cationic drug is a simple and efficient method of preparing a colloidal drug carrier system. Dextran sulfate, with a negatively charged sulfate group, was reacted in an acetate buffer solution of pH 3 with positively charged 1° amine, 2° amine, 3° amine, piperazine, and piperidine structures from 24 small-molecule drugs. The electrolyte complex was formed from 15 drugs, 63% of those tested. The tendency to form the electrolyte complex was in the order of piperazine and piperidine >3° amine >>2° amine. The drugs with the 1° amine structure failed to form an electrolyte complex. The mean particle sizes were in the range of 50-740 nm, and most of them showed a submicron colloidal dispersion of <400 nm. Regarding drug encapsulation efficiency (%), 11 drugs with piperazine, piperidine, and 3° amine structures showed 60-98% efficiency, which was fairly high. The results suggest that directly forming the electrolyte complex with dextran sulfate yields promising structural attributes as a submicron colloidal drug carrier system.

Recent Advances in Nanocapsule: Types, Preparation Methods and Characterizatio

Nanocapsules are submicroscopic colloidal drug carrier systems consist of a liquid/solid core in which the drug, gene, protein, and other substances are incorporated into the interior cavity that is surrounded by a distinctive polymeric membrane. Polymers like collagen, albumin, and gelatin are mainly using polymers in nanocapsule formulations. Nanocapsules can serve as nano-sized drug carriers to achieve controlled release as well as efficient drug targeting. The process is used to improve the poor aqueous drug solubility, taste, stabilizing drugs by protecting the molecule from the environment, providing the desired pharmacokinetic profile, allowing controlled release, as well as facilitating oral administration. Capsules are generally prepared between the range of 100 and 1000 nm. Their release and degradation properties largely depend on the composition and the structure of the capsule walls. The dispersion stability of nanocapsules determined by the surfactant, nature of the outer coating. This review describes various facts of nanocapsule drug delivery systems in relation to the method of formulation, characterization, potential benefits and risks, and pharmaceutical applications in drug delivery.

Biomedical applications of microemulsion through dermal and transdermal route

Microemulsions are thermodynamically stable, transparent, colloidal drug carrier system extensively used by the scientists for effective drug delivery across the skin. It is a spontaneous isotropic mixture of lipophilic and hydrophilic substances stabilized by suitable surfactant and co-surfactant. The easy fabrication, long-term stability, enhanced solubilization, biocompatibility, skin-friendly appearance and affinity for both the hydrophilic and lipophilic drug substances make it superior for skin drug delivery over the other carrier systems. The topical administration of most of the active compounds is impaired by limited skin permeability due to the presence of skin barriers. In this sequence, the microemulsion represents a cost-effective and convenient drug carrier system which successfully delivers the drug to and across the skin. In the present review work, we compiled various attempts made in last 20 years, utilizing the microemulsion for dermal and transdermal delivery of various drugs. The review emphasizes the potency of microemulsion for topical and transdermal drug delivery and its effect on drug permeability.

Therapeutic potential of drug delivery by means of lipid nanoparticles: reality or illusion?

Solid lipid nanoparticles (SLN) are colloidal drug carrier systems that contribute several properties required from a sophisticated drug delivery system for increasing drug bioavailability and providing effective therapy. Many advantages of SLN have been reported over traditional dosage forms and their colloidal counterparts in the studies since the early 1990s. They were optimized for oral drug delivery for the first time. The first SLN formulations were produced by reducing the particle size of solid lipid microparticles by spray congealing technique in the late 1980s. Then, studies have been continued investigating for their different administration routes else including parenteral, transdermal, ocular, nasal, respiratory etc. Their foremost qualifications such as their biocompatible nature and high drug entrapment efficiency make them promising colloidal drug carrier systems for the effective treatment of serious disasters like genetic disorders and cancer. In this review, therapeutic potential of drug delivery of SLN and nanostructured lipid carriers (NLC, the second generation of SLN) are summarized considering researches and patents on their administration via different routes and their preparations in the pharmaceutical market.

Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain.

CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting. Several approaches have been investigated to allow therapeutics to cross the BBB. As the molecular structure of the BBB is better elucidated, several key approaches for brain targeting include physiological transport mechanisms such as adsorptive-mediated transcytosis, inhibition of active efflux pumps, receptor-mediated transport, cell-mediated endocytosis, and the use of peptide vectors. Drug-delivery approaches comprise delivery from microspheres, biodegradable wafers, and colloidal drug-carrier systems (e.g., liposomes, nanoparticles, nanogels, dendrimers, micelles, nanoemulsions, polymersomes, exosomes, and quantum dots). The current review discusses the latest advancements in these approaches, with a major focus on articles published in 2015 and 2016. In addition, we also cover the alternative delivery routes, such as intranasal and convection-enhanced diffusion methods, and disruption of the BBB for brain targeting.

Polymers in Drug Delivery

Polymers are being used extensively in drug delivery due to their surface and bulk properties. They are being used in drug formulations and in drug delivery devices. These drug delivery devices may be in the form of implants for controlled drug delivery. Polymers used in colloidal drug carrier systems, consisting of small particles, show great advantage in drug delivery systems because of optimized drug loading and releasing property. Polymeric nano particulate systems are available in wide variety and have established chemistry. Non toxic, biodegradable and biocompatible polymers are available. Some nano particulate polymeric systems possess ability to cross blood brain barrier. They offer protection against chemical degradation. Smart polymers are responsive to atmospheric stimulus like change in temperature; pressure, pH etc. thus are extremely beneficial for targeted drug delivery. Some polymeric systems conjugated with antibodies/specific biomarkers help in detecting molecular targets specifically in cancers. Surface coating with thiolated PEG, Silica-PEG improves water solubility and photo stability. Surface modification of drug carriers e.g. attachment with PEG or dextran to the lipid bilayer increases their blood circulation time. Polymer drug conjugates such as Zoladex, Lupron Depot, On Caspar PEG intron are used in treatment of prostate cancer and lymphoblastic leukemia. Polymeric Drug Delivery systems are being utilized for controlled drug delivery assuring patient compliance.

Recent Techniques and Patents on Solid Lipid Nanoparticles as Novel Carrier for Drug Delivery.

The various approaches have been utilized in the treatment of a variety of diseases by applying drug delivery system such as polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions and micellar solutions. Recently, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid-drug conjugates (LDCs) have been exploited as a carrier of lipophilic and hydrophilic/amphiphilic substances for invasive and non-invasive routes of delivery. SLNs are colloidal drug carrier system and are like nanoemulsion, however, the lipid content in SLNs is solid in nature. These novel type of lipid nanoparticles with solid matrix offers to develop new prototype therapeutics in drug delivery, which could be used for controlled release, drug targeting, gene therapy, physical and chemical stability and site-specific drug delivery and thereby attracted the research groups worldwide. This manuscript overviews the recent patents, advantages, formulation techniques, stability aspects and applications of SLNs.

Pharmacokinetics of temoporfin-loaded liposome formulations: Correlation of liposome and temoporfin blood concentration

Liposomal formulations of the highly hydrophobic photosensitizer temoporfin were developed in order to overcome solubility-related problems associated with the current therapy scheme. We have incorporated temoporfin into liposomes of varying membrane composition, cholesterol content, and vesicle size. Specifically, two phosphatidyl oligoglycerols were compared to PEG2000-DSPE with respect to the ability to prolong circulation half life of the liposomal carrier. We measured the resulting pharmacokinetic profile of the liposomal carrier and the incorporated temoporfin in a rat model employing a radioactive lipid label and 14C-temoporfin. The data for the removal of liposomes and temoporfin were analyzed in terms of classical pharmacokinetic theory assuming a two-compartment model. This model, however, does not allow in a straightforward manner to distinguish between temoporfin eliminated together with the liposomal carrier and temoporfin that is first transferred to other blood components (e. g. plasma proteins) before being eliminated from the blood. We therefore additionally analyzed the data based on two separate one-compartment models for the liposomes and temoporfin. The model yields the ratio of the rate constant of temoporfin elimination together with the liposomal carrier and the rate constant of temoporfin elimination following the transfer to e. g. plasma proteins. Our analysis using this model demonstrates that a fraction of temoporfin is released from the liposomes prior to being eliminated from the blood. In case of unmodified liposomes this temoporfin release was observed to increase with decreasing bilayer fluidity, indicating an accelerated temoporfin transfer from gel-phase liposomes to e. g. plasma proteins. Interestingly, liposomes carrying either one of the three investigated surface-modifying agents did not adhere to the tendencies observed for unmodified liposomes. Although surface-modified liposomes exhibited improved pharmacokinetic properties with regard to the liposomal carrier, an enhanced temoporfin loss and elimination from the PEGylated-liposomes was observed. This effect was more pronounced for PEGylated liposomes than for the two oligo-glycerols. Our combined experimental–theoretical approach for in vivo plasma re-distribution of liposomal drugs may help to optimize colloidal drug carrier systems.

Preparation of Nanoemulsions and Solid Lipid Nanoparticles by Premix Membrane Emulsification

In an attempt to overcome problems of conventional high-energy preparation processes for colloidal drug carrier systems, premix membrane emulsification was investigated for the first time as an alternative low-energy input process for the preparation of pharmaceutical nanoemulsions and solid lipid nanoparticles. The effect of process parameters on dispersions based on nonpolar lipids (medium-chain triglycerides, soybean oil, and trimyristin) and different emulsifiers (sodium dodecyl sulfate, poloxamer 188, polyglyceryl-10-laurate, and sucrose laurate) was studied in a small-volume device and a larger scale-up approach. For emulsions and suspensions, mean particle sizes in a range from about 100 to 200 nm were observed for monomodal to monodisperse particle size distributions after 21 cycles of extrusion through polycarbonate membrane filters. As the mass ratio of matrix lipid to emulsifier (4:3, w/w concentrations) usually applied for the preparation of stable colloidal lipid particles was quite high, the amount of emulsifier in the dispersions was minimized. It was observed that the minimal concentration of emulsifier increased with decreasing membrane pore size. The possibility to prepare colloidal drug carrier systems with a high concentration of matrix lipid (up to 20%) by an optimized membrane extrusion process offers new opportunities for the processing of sensitive substances.

Solid Lipid Nanoparticle: A Review

– Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine and research as well as in othervaried sciences. Solid lipid nanoparticle (SLN) dispersions have been proposed as a new type of colloidal drug carrier system suitable for intravenous administration. The system consists of spherical solid lipid particles in the nanometer ranges, which are dispersed in water or in aqueous surfactant solution. It is identical to an oil-in-water emulsion for parenteral nutrition but the liquid lipid (oil) of the emulsion has been replaced by a solid lipid, i.e., yielding Solid Lipid Nanoparticles. Different production methods which are suitable for large scale production and applications of solid lipid nanoparticles are described. Appropriate analytical techniques for characterization of solid lipid nanoparticles like photon correlation spectroscopy, scanning electron microscopy, differential scanning calorimetry are highlighted. Aspects of solid lipid nanoparticles route of administration and their biodistribution are also incorporated. If appropriately investigated, solid lipid nanoparticles may open new vistas in therapy of complex diseases. Keywords–– Solid lipid nanoparticles (SLN), colloidal drug carriers, homogenization.

Cryogenic transmission electron microscopy (cryo-TEM) for studying the morphology of colloidal drug delivery systems

Cryogenic transmission electron microscopy (cryo-TEM) has evolved into an indispensable tool for the characterization of colloidal drug delivery systems. It can be applied to study the size, shape and internal structure of nanoparticulate carrier systems as well as the overall colloidal composition of the corresponding dispersions. This review gives a short overview over the instrumentation used in cryo-TEM experiments and over the sample preparation procedure. Selected examples of cryo-TEM studies on colloidal drug carrier systems, including liposomes, colloidal lipid emulsions, solid lipid nanoparticles, thermotropic and lyotropic liquid crystalline nanoparticles, polymer-based colloids and delivery systems for nucleic acids, are presented in order to illustrate the wealth of information that can be obtained by this technique.

Freeze drying of human serum albumin (HSA) nanoparticles with different excipients

Freeze drying is a suitable technique to improve the long-term storage stability of colloidal drug carrier systems such as nanoparticles. Aim of this study was to systematically evaluate excipients for the freeze drying and long-term stability of albumin-based nanoparticles. In our study, nanoparticles made of human serum albumin (HSA) were freeze dried in the presence of different cryoprotective agents and after reconstitution were evaluated with regard to their physico-chemical characteristics. Empty, doxorubicin-loaded, and PEGylated nanoparticles were prepared and were freeze dried in the presence of different concentrations of sucrose, trehalose, and mannitol, respectively. The samples were physico-chemically characterised with regard to lyophilisate appearance, particle size, and polydispersity using photon correlation spectroscopy. For evaluation of long-term stability, the samples were stored at 2–8, 25, and 40 °C over predetermined time intervals. In the absence of cryoprotectants, particle growth was observed in all freeze-dried formulations. In the presence of sucrose, mannitol, and trehalose aggregation of HSA nanoparticles during the freeze-drying procedure was prevented. Although all of the excipients were identified to be suitable stabilisers for freeze drying of HSA nanoparticles, sucrose and trehalose were superior to mannitol, especially with regard to the long-term storage stability results.

Method for Quantifying the PEGylation of Gelatin Nanoparticle Drug Carrier Systems Using Asymmetrical Flow Field-Flow Fractionation and Refractive Index Detection

The PEGylation of colloidal drug carrier systems protects them from a rapid clearance from the blood stream and therefore prolongs their plasma half-lives. This fundamental concept is nowadays widely applied whereas the analytical description, i.e., the quantification of the PEGylation process, is still challenging due to the poor spectrophotometrical properties of PEG. The aim of this work is to quantify the PEGylation process of gelatin nanoparticles by utilizing the combination of asymmetrical flow field-flow fractionation (AF4) and refractive index (RI) detection and to demonstrate the potential of AF4 in the work with colloidal drug carrier systems. An AF4 separation mechanism of gelatin nanoparticles and PEG was developed without further sample preparation. After separation, the PEGylation could be directly quantified from the respective RI data and a threshold of a maximum amount of PEG that can be bound onto the surface of the nanoparticles could be determined. The PEGylation could be further visualized by atomic force microscopy (AFM). In sum, the presented results show the successful application of AF4 in the field of colloidal drug carrier systems, and in combination with AFM, both techniques can be stated as promising tools for the future analysis of colloidal drug carrier systems.

Comparison of stratum corneum penetration and localization of a lipophilic model drug applied in an o/w microemulsion and an amphiphilic cream

Vehicle dependent effects on the penetration behavior of drugs following topical application are well known from the literature. In this context, many reports concerning the enhancing activities for hydrophilic as well as lipophilic substances by colloidal drug carrier systems, particularly microemulsions, are available. However, there is little knowledge about the localization of the drugs within the skin and the stratum corneum, respectively. In the present study, the lipophilic dye curcumin incorporated in an oil-in-water microemulsion and in an amphiphilic cream was applied onto the skin of human volunteers. Using the method of tape stripping to remove the stratum corneum (SC), the depth profiles of the dye within the horny layer were compared. Applying the microemulsion, a deeper part of the SC was accessible by a number of 20 tapes removed and significantly smaller amounts of curcumin were found on the skin surface. Also differences in the distribution and localization of the dye within the stratum corneum were observed by laser scanning microscopy. Furthermore, curcumin was detected in hair follicles. It was obvious that the microemulsion led to a penetration into the complete follicular infundibula, whereas, following application of the cream, a fluorescence signal was only received from the follicular orifices.

Novel physically structured lipid matrices of beeswax and a homolipid from Capra hircus (goat fat): a physicochemical characterization for application in drug delivery

Lipid based materials are fast becoming the carrier of choice for delivery of new chemical entities and active agents. It is important to know the thermal characteristics, crystal habit, texture and appearance of a new lipid matrix when determining its suitability for use in pharmaceutical formulations. In this study, physically structured lipid matrices containing various proportions (25% w/w, 50% w/w and 75% w/w) of beeswax in a novel homolipid from Capra hircus (goat fat) were prepared by fusion, and subjected to thermal treatments in a differential scanning calorimeter (DSC) to obtain the thermal characteristics. Further characterization of the lipid matrices was performed by X-ray diffraction, polarized light microscopy (PLM) and transmission electron microscopy (TEM). Kinetics of crystallization of the molten lipid matrices was studied in an isothermal heat conduction microcalorimeter (IMC). Analysis of thermal data from DSC indicated that the physically structured lipid matrices revealed varied melting peaks between those of the pure lipids. PLM observation exhibited qualitatively different textures for the different structured lipid matrices. The lipid matrix containing 50% w/w of beeswax presented an interference at 2θ = 1.2° d = 73.63 A different from those of the two pure lipids. The lipid matrix containing 75% w/w of beeswax showed a change in crystallization behavior after 34 h. Crystallization kinetic analysis indicated that the structured lipid matrix containing 50% w/w beeswax possessed the highest Avrami kinetic exponent n. Results obtained indicated that mixtures of beeswax and goat fat produced matrices composed of mixtures of crystals alongside mixed crystals with imperfections necessary for increased drug loading and retention capacities. The matrix containing 50% w/w of beeswax possessed ideal crystal properties for the formulation of colloidal and microparticulate lipid drug carrier systems of drug delivery.

The obtention of an oil/water nanoemulsion containing the Calceolaria chelidonioides flowers ethanol extract and its skin hydration power

Nanoemulsions are biphasic systems with droplet size in the nanometric scale (20–200nm). Oil/water nanoemulsions are promising colloidal drug carrier systems for diverse therapeutic applications as topical, intravenous, oral and ocular [1]. They are non-equilibrium systems, a high energy input generally from mechanical devices or from the chemical potential of the components, is required for their formation [2]. In this work we prepared an oil/water nanoemulsion with the ethanolic extract obtained from flowers of Calceolaria chelidonioides 5% with droplet size of 45,46±3,64nm and high stability using a classical macroemulsion protocol by mixing two formulation concepts, the H.L.B. and the phase diagram, to choose the best non-ionic surfactant match. Calceolaria chelidonioides is an original Brazilian plant belonging to the Scrophulariaceae family. This plant has been studied in our group and we were able to identify its antimicrobial and antioxidant properties [3]. We evaluate this nanoemulsion skin hydration power in vivo with female volunteers between (20–40 years old). The measurement of the skin humidity was carried out by a Corneometer® CM820 using the capacitance method, before and 10, 20, 30, 45 minutes after the administration. Two moisturizing comercial products well known by its properties, Nivea Soft® from Nivea® and Ictyane® from Ducray® were used as control, and the formulated nanoemulsion without the plant active was evaluated. The C. chelidonioides' nanoemulsion showed some interesting skin hydration actitvity higher than Nivea Soft® cream, especially after 45 minutes, showing an increase of 25% in skin hydration. However, the most important hydration power was obtained with the nanoemulsion base which showed 30% of increase after 45 minutes.

Transport of Zidovudine-and Lamivudine-Loaded Polybutylcyanoacrylate and Methylmethacrylate-Sulfopropylmethacrylate Nanoparticles across the In Vitro Blood-Brain Barrier: Characteristics of the Drug-D

Transport study of zidovudine (AZT) and lamivudine (3TC) loaded on polybutylcyanoacrylate (PBCA) and methylmethacrylate-sulfopropylmethacrylate (MMA-SPM) nanoparticles (NPs) across the in vitro blood-brain barrier (BBB) model system was presented. Through primary culture, confluent monolayer of bovine brain-microvascular endothelial cells (BBMECs) with the feature of cellular homogeneity and tight intercellular junction was demonstrated by immunocytochemical fluorescent method. Besides, for the colloidal drug-carrier system, average diameters of the two nearly monodispersed PBCA and MMA-SPM nanospheres were, respectively, about 92 nm and 78 nm. The amount of AZT and 3TC across the current BBMEC monolayer in carrier-incorporated system was much higher than that in non-carrier system, suggesting sufficient amelioration in drug transport by employing the NP carriers for brain-targeting delivery. Comparing PBCA NPs with MMA-SPM NPs, the amount of drug (AZT and 3TC) across the in vitro BBB system for the former was in excess of 1.5 times that for the latter.

Towards mitochondria-specific delivery of apoptosis-inducing agents: DQAsomal incorporated paclitaxel

DQAsomes have been developed by us as the first mitochondria-specific colloidal drug carrier system. Previously we have shown that DQA-somes meet all criteria for a mitochondria-targeted DNA delivery system. Here we describe for the first time the use of DQAsomes for encapsulating low-molecular weight compounds. As a model drug we have used paclitaxel, which has recently been shown to trigger apoptosis in tumor cells by acting directly on mitochondria. We demonstrate that paclitaxel can be incorporated into DQAsomes at an approximate ratio of 0.5 mol paclitaxel per mol dequalinium. Following an extensive physicochemical characterization of paclitaxel-loaded DQAsomes using three different electron microscopic techniques we tested in a preliminary study the ability of paclitaxel-loaded DQAsomes to inhibit the growth of human colon cancer cells in nude mice.