9 research outputs found
In vivo optical monitoring of transcutaneous delivery of calcium carbonate microcontainers
We have developed a method for delivery of biocompatible CaCO3 microcontainers (4.0 ± 0.8 µm) containing Fe3O4 nanoparticles (14 ± 5 nm) into skin in vivo using fractional laser microablation (FLMA) provided by a pulsed Er:YAG laser system. Six laboratory rats have been used for the microcontainer delivery and weekly monitoring implemented using an optical coherence tomography and a standard histological analysis. The use of FLMA allowed for delivery of the microcontainers to the depth about 300 μm and creation of a depot in dermis. On the seventh day we have observed the dissolving of the microcontainers and the release of nanoparticles into dermis
Улучшение деградации лекарственных носителей на основе ватерита внутри волосяных фолликулов с помощью сонофореза
Intrafollicular drug delivery is beneficial in terms of both localized therapy of relevant skin disorders and systemic transportation of bioactive molecules. Vaterite particles are capable of loading and delivering various substances to hair follicles. Possibility to control the duration of their intrafollicular degradation can improve such a particulate delivery system. Here, we propose the use of sonophoresis (1 MHz, 1 W/cm2) to accelerate the resorption of vaterite carriers inside the hair follicles of rats in vivo. The effect of sonication is demonstrated utilizing optical coherence tomography monitoring of the skin and scanning electron microscopy investigation of the plucked hairs. A nine-minute post-treatment of skin in the site of particle delivery allowed us to almost halve the time of their degradation
Key Points in Remote-Controlled Drug Delivery: From the Carrier Design to Clinical Trials
The increased research activity aiming at improved delivery of pharmaceutical molecules indicates the expansion of the field. An efficient therapeutic delivery approach is based on the optimal choice of drug-carrying vehicle, successful targeting, and payload release enabling the site-specific accumulation of the therapeutic molecules. However, designing the formulation endowed with the targeting properties in vitro does not guarantee its selective delivery in vivo. The various biological barriers that the carrier encounters upon intravascular administration should be adequately addressed in its overall design to reduce the off-target effects and unwanted toxicity in vivo and thereby enhance the therapeutic efficacy of the payload. Here, we discuss the main parameters of remote-controlled drug delivery systems: (i) key principles of the carrier selection; (ii) the most significant physiological barriers and limitations associated with the drug delivery; (iii) major concepts for its targeting and cargo release stimulation by external stimuli in vivo. The clinical translation for drug delivery systems is also described along with the main challenges, key parameters, and examples of successfully translated drug delivery platforms. The essential steps on the way from drug delivery system design to clinical trials are summarized, arranged, and discussed
Optical clearing of tissues: Issues of antimicrobial phototherapy and drug delivery
In the modern world, with a poor environmental situation, there is a certain ‘‘erasure” of the boundaries between pathogenic, opportunistic microorganisms and commensals, the number of antibiotic-resistant bacterial strains is growing. The microbiome of the human body is made up of more than 500 types of microorganisms, representing an integral ecological system, which is in a state of dynamic equilibriumwith macroorganism. Colonization of various biotopes is carried out by the formation of a biofilm, which represents several layers of microorganisms covered with a common glycocalyx and enclosed in a highly hydrated exopolysaccharide-mucin matrix. Under certain conditions, opportunistic bacteria can become causative agents of purulentinflammatory diseases, i.e. the mechanism of autoinfection is realized with a decrease in the body’s resistance or their translocation into unusual biotopes
Key parameters for size- and shape-controlled synthesis of vaterite particles
Calcium carbonate (CaCO3) has attracted scientific attention due to its essential role in both inorganic and bioorganic chemistry. Vaterite is the least thermodynamically stable CaCO3 polymorph and has elicited great interest as an advanced biomaterial for tissue engineering, drug delivery, and a broad range of personal care products. Numerous methods of vaterite particle synthesis with different sizes and morphologies, have highlighted the submicron porous particles of spherical or ellipsoidal shape as the most useful ones. In this regard, the current study is aimed at development of a reliable method for synthesis of such structures. Herein, submicron vaterite partitles are synthesized by dropwise precipitation from saturated sodium carbonate and calcium chloride solutions in the presence of ethylene glycol while manipulating the concentration ratios of reagents. We demonstrate that our novel technique named "dropwise precipitation" leads to changing calcium concentrations in the reaction solution at each moment affecting the crystallization process. The proposed technique allows routine obtainment of vaterite particles of a required shape, either spherical or ellipsoidal, and a controlled size in the range from 0.4 to 2.7 mu m and (0.4 x 0.7) to (0.7 x 1.1) mu m, respectively. The key parameters influencing the size, shape, and percent of vaterite fraction for synthesized CaCO3 particles are discussed
Transdermal platform for the delivery of the antifungal drug naftifine hydrochloride based on porous vaterite particles
Development of a skin-targeted particulate delivery system providing an extended or sustained release of the payload and a localized therapeutic effect is one of the main challenges in the treatment of fungal skin infections. In the topical administration of antifungals, the drug should penetrate into the stratum corneum and lower layers of the skin in effective concentrations. Here, we introduce biodegradable calcium carbonate carriers containing 4.9% (w/w) of naftifine hydrochloride antimycotic allowing the efficient accumulation into the skin appendages. The proposed particulate formulation ensures the enhancement of the local drug concentration, prolongation of the payload release, and control over its rate. Furthermore, it provides a highly efficient cellular uptake and excellent bioavailability in vitro and enables a deep penetration during transfollicular delivery in vivo. The enhanced fungi growth inhibition efficiency of naftifine-loaded calcium carbonate carriers compared to naftifine solution makes them a promising alternative to creams and gels currently existing on the market
Optical monitoring of adipose tissue destruction under encapsulated lipase action
Enzymatic destruction of adipose tissue has been achieved by encapsulation of lipase into the polymeric microcapsules. Adipose tissue destruction was delayed while lipase is encapsulated comparing with the direct lipase action as demonstrated by optical microscopy and optical coherence tomography in in vitro studies. Raman spectroscopy confirms that triglycerides in fat tissue were cleaved into free fatty acids, glycerol, and possible di- and monoglyceride residues. The results underpin the concept of local and controlled treatment of tissues via encapsulation. Effect of lipase encapsulation into the polymeric microcapsules on adipose tissue destruction compared to free lipase application
A simple non-invasive approach toward efficient transdermal drug delivery based on biodegradable particulate system
Transdermal administration via skin appen- dages enables both localized and systemic drug delivery, as well as minimizes incidental toxicity. However, the design of an appropriate effective method for clinical use remains challenging. Here, we introduce calcium carbonate-based carriers for the transdermal transportation of bioactive substances. The proposed system presents easily manufactur- able biodegradable particles with a large surface area enabling a high payload ability. Topical application of submicron porous CaCO3 particles in rats followed by the therapeutic ultrasound treatment results in their deep penetration through the skin along with plentiful filling of the hair follicles. Exploiting the loading capacity of the porous particles, we demonstrate efficient transportation of a fluorescent marker along the entire depth of the hair follicle down the bulb region. In vivo monitoring of the carrier degradation reveals the active dissolution/ recrystallization of CaCO3 particles, resulting in their total resorption within 12 days. The proposed particulate system serves as an intrafollicular depot for drug storage and prolonged in situ release over this period. The urinary excretion profile proves the systemic absorption of the fluorescent marker. Hence, the elaborated transdermal delivery system looks promising for medical applications. The drug delivery to different target regions of the hair follicle may contribute to regenerative medicine, immunomodulation, and treatment of various skin disorders. In the meantime, the systemic uptake of the transported drug opens an avenue for prospective delivery routes beyond the scope of dermatolog
In vivo optical monitoring of transcutaneous delivery of calcium carbonate microcontainers
We have developed a method for delivery of biocompatible CaCO3 microcontainers (4.0 ± 0.8 µm) containing Fe3O4 nanoparticles (14 ± 5 nm) into skin in vivo using fractional laser microablation (FLMA) provided by a pulsed Er:YAG laser system. Six laboratory rats have been used for the microcontainer delivery and weekly monitoring implemented using an optical coherence tomography and a standard histological analysis. The use of FLMA allowed for delivery of the microcontainers to the depth about 300 μm and creation of a depot in dermis. On the seventh day we have observed the dissolving of the microcontainers and the release of nanoparticles into dermis