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INCAPSULAZIONE DI PRINCIPI ATTIVI IN MICROPARTICELLE LIPIDICHE PER SOMMINISTRAZIONE TOPICA ED INALATORIA
No full textThe aim of my project is the production of solvent‐free carriers for drug
delivery based on lipid microparticles. In particular, the encapsulation of
sunscreen agents for topical administration and the entrapment of
cortisteroids for inhalation therapy in solid lipidic microparticles (SLMs) were
investigated. These carriers were prepared by melt techniques and spraycongealing
methods.
An essential requirement for the efficacy and safety of sunscreen agents is a
high photostability, since the light‐induced degradation of the UV filter not
only decreases the expected protective power but can also lead to the
accumulation on the skin of harmful photolytic products.
Recent investigations have shown that in rat as well as in man, the UV‐B (290‐
320nm) filter methylbenzylidene camphor (4‐MBC) is systemically adsorbed
after topical application. This aspect should be considered with attention,
since in‐vitro animal studies have reported on the estrogenic activity of 4‐
MBC. Therefore, there is a need for new systems able to minimize the skin
penetration of 4‐MBC. The results obtained demonstrated that encapsulation
of 4‐MBC in lipidic microparticles, after their introduction in a model cream,
decreases the percutanous penetration of the sunscreen, thereby minimising
its systemic uptake and the potentially associated toxicological risks. The data
reported also showed that although the in vitro test represents a simple model
for percutaneous penetration studies, in‐vivo investigations are necessary for
more realistic assessment of the factors affecting the degree of skin adsorption.
Moreover, published reports have demonstrated that butyl
methoxydibenzoylmethane (BMDBM), the most efficient and widely used
UV‐A filter, is not sufficiently photostable decomposing and generating free
radical when illuminated with simulated sun‐light. In order to reduce the
sunscreen photodegradation, the incorporation of BMDBM into solid lipid
microparticles together with photostabilizers (i.e. 4‐methylbenzylidene
camphor and octocrylene) was investigated. From the results obtained the
SLMs containing BMDBM together with the photostabilizer were more
effective in enhancing the UV‐A filter photostability than SLMs loaded with
BMDBM alone.
Moreover, lipid microparticles loaded with BMDBM alone were prepared to
evaluated the UV filter skin permeation in vivo, by the tape stripping method.
Studies were also undertaken to develop SLMs loaded with high amounts of
BMDBM. The microparticles were produced by the classical melt dispersion
method and the spray congealing technique with pneumatic atomizer.
However, release studies indicated that spray congealing enabled a more
efficient modulation of BMDBM release from the SLMs. Moreover, the SLMs
produced by spray congealing achieved a more marked reduction in BMDBM
photodecomposition. Therefore, the spray congealing technique was found to
achieve rapid and solvent free production of SLMs with a high BMDBM
loading capacity.
For the inhalation therapy, the aim of project was to find optimal conditions
for the production of SLMs containing Budesonide for drug‐targeting to the
lung, The study involved the charaterization in terms of morphology (shape,
surface and roughness) and size of the SLMs produced, determination of the
controlled release by flow through apparatus in different media and finally
evaluation of the regional lung deposition of particles by MSLI (Multi‐stage
liquid impinger). The study has shown that solid lipid microparticles may
provide a useful approach to controlled release respiratory therapy
Comparative evaluation of different substrates for the in vitro determination of sunscreen photostability: spectrophotometric and HPLC analyses
No full textSynopsis Polymethylmethacrylate (PMMA) plates and TransporeTM tapes were compared as substrates for the in vitro evaluation of photostability of commercial sunscreen products. The sun care preparations were applied respectively on TransporeTM tapes and PMMA plates and their sun protection factors (SPF) and UVA protection parameters [UVA/UVB ratio, critical wavelength, UVA protection factor (UVA-PF)] were measured by transmission spectroscopy, before and after irradiation with simulated sunlight. No significant differences were observed in the UV protection parameters measured on TransporeTM tapes or PMMA plates, before exposure to the solar simulator. Conversely, after irradiation, the SPF values of the sun care products exhibited marked variations between the two substrates, the decrease in SPF being greater on PMMA plates (31.3-63.1%) than on TransporeTM tapes (10.4-23.8%). Differences between the two substrates were detected also for the UVA protection parameters, although they were significant only for the UVA-PF. The tested samples were assayed also by high-performance liquid chromatography (HPLC) to assess the extent of photodegradation of the UV filters present in the examined formulations. The results showed that for the PMMA plates, the light-induced decrease in SPF, as determined by spectrophotometry, fitted well with the percentage loss of ethyl hexyl methoxycinnamate (the only photounstable UVB filter present) measured by HPLC. Moreover, for the PMMA substrate, the UVA-PF percentage reduction was consistent with the percentage degradation of butyl methoxydibenzoylmethane (the only photounstable UVA filter present) determined by HPLC. On the other hand, poor correlation between spectrophotometric and HPLC analyses was observed on TransporeTM tapes. Therefore, PMMA plates are more reliable than TransporeTM tapes as substrates for in vitro photodegradation tests of sunscreen products by transmission spectroscopy. © 2009 Society of Cosmetic Scientists and the Société Française de Cosmétologie
Incorporation in Lipid Microparticles of the UVA Filter, Butyl Methoxydibenzoylmethane Combined with the UVB Filter, Octocrylene: Effect on Photostability
No full textThe aim of this study was to reduce the photoinstability of butyl methoxydibenzoylmethane (BMDBM), the most widely used UVA filter, by incorporating it in lipid microparticles (LMs) alone or together with the UVB filter octocrylene (OCR), acting also as photostabilizer. Microparticles loaded with BMDBM or with combined BMDBM and OCR were produced by the hot emulsion technique, using glyceryl behenate as lipid material and poloxamer 188 as surfactant. The LMs were characterized by release studies, scanning electron microscopy and powder X-ray diffractometry. The BMDBM and OCR loading was 15.2% and 10.6%, respectively. In order to reproduce the conditions prevalent in commercial sunscreen products, the photoprotective efficacy of the LMs was evaluated after their introduction in a model cream (oil-in-water emulsion) containing a mixture of UVA and UVB filters. A small but statistically significant decrease in BMDBM photodegradation was obtained when the UVA filter was encapsulated alone into the LMs (the extent of degradation was 28.6% ± 2.4 for non-encapsulated BMDBM and 26.0% ± 2.5 for BMDBM-loaded microparticles). On the other hand, the co-loading of OCR in the LMs produced a more marked reduction in the light-induced decomposition of microencapsulated BMDBM (the UVA filter loss was 21.5% ±2.2). Therefore, incorporation in lipid microparticles of BMDBM together with the sunscreen OCR is more effective in enhancing the UVA filter photostability than LMs loaded with BMDBM alone
Solid lipid microparticles for the stability enhancement of the polar drug N6-cyclopentyladenosine
No full textThe objective of this study was to prepare solid lipid microparticles (SLMs) loaded with the polar adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA). The microparticles were produced by the conventional hot emulsion technique, using different lipidic carriers (tristearin, glyceryl behenate and stearic acid) and hydrogenated phosphatidylcholine as the surfactant. The controlled release of CPA was achieved only with stearic acid microparticles. This phenomenon has been attributed to direct acid-base interactions between the basic nitrogen atoms of CPA and stearic acid. These SLMs were characterized by release studies, scanning electron microscopy and powder X-ray diffraction analyses.
The obtained particles showed proper features in terms of morphology and size distribution (3.2-10.3 microm), with a drug loading of 0.15±0.04%.
The influence of the SLMs carrier system on CPA stability was investigated in vitro using human whole blood. The degradation kinetic of microparticle-entrapped CPA was significantly lower from that measured for the free CPA. The overall results indicate that it was possible to achieve the encapsulation and controlled release of a polar drug, such as CPA, within a lipid matrix without resorting to the complex methods generally used for the preparation of these systems
Solid lipid microparticles for the stability enhancement of a dopamine prodrug
No full textDopamine supplementations in the brain alleviates the neurological symptoms associated with the Parkinson’s disease, but several difficulties hamper its oral or peripheral administration for clinical uses: (i) inability to cross the blood brain barrier, (ii) induction of dangerous unwanted effects in peripheral tissues, (iii) extensive hepatic metabolism when orally administered. The enhancement of dopamine stability in physiologic environments and its brain targeting appear therefore useful and a challenging aspect in formulation development. We propose a new study concerning the preparation and characterization of solid lipid microparticles based on tristearin as sustained delivery system for dopamine. The microparticles were produced by the conventional hot emulsion technique. The synthesis of a new valeroyl ester of dopamine (3,4-O-divaleroyl-dopamine, DVD) was necessary to obtain its encapsulation in the microparticles. DVD appeared totally hydrolized to dopamine in human plasma within 40 seconds. The amount of encapsulated DVD in microparticles was 2.67 1.2%. The mean diameter of particles was 14.2 4.8 μm. The DVD release from microparticles was characterized by an initial burst of 20% of incorporated prodrug and a continuous slow release thereafter. The microparticles were found able to stabilize DVD in its solid form. We have finally demonstrated that DVD encapsulated in the microparticles degraded in human plasma with a markedly reduced rate in comparison with free prodrug. The DVD loaded microparticles appear therefore a promising system for dopamine uptake in the brain, following the nasal administration
Incorporation of the polar antiischemic drug N6-cyclopentyladenosine in solid lipid microparticles
No full textThe objective of this study was to prepare solid lipid microparticles (SLMs) loaded with the polar adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA). The microparticles were produced by the conventional hot emulsion technique, using different lipidic carriers (tristearin, glyceryl behenate and stearic acid) and hydrogenated phosphatidylcholine as the surfactant. The controlled release of CPA was achieved only with stearic acid microparticles. This phenomenon has been attributed to direct acid-base interactions between the basic nitrogen atoms of CPA and stearic acid. These SLMs were characterized by release studies, scanning electron microscopy and powder X-ray diffraction analyses. The obtained particles showed proper features in terms of morphology and size distribution ( 3.2 – 10.3 μm), with a drug loading of 0.15 +/- 0.04%. The influence of the SLMs carrier system on CPA stability was investigated in vitro using human whole blood. The degradation kinetic of microparticle-entrapped CPA was significantly lower from that measured for the free CPA. The overall results indicate that it was possible to achieve the encapsulation and controlled release of a polar drug, such as CPA, within a lipid matrix without resorting to the complex methods generally used for the preparation of these systems
Influence of solid lipid microparticle carriers on skin penetration of the sunscreen agent, 4-methylbenzylidene camphor
No full textThe objective of this study was to prepare lipid microparticles (LMs) loaded with the sunscreen agent, 4-methylbenzylidene camphor (4-MBC), to achieve decreased skin penetration of this UV filter. The microparticles were produced by the melt dispersion technique using tristearin as lipidic material and hydrogenated phosphatidylcholine as the surfactant. The obtained microparticles were characterized by scanning electron microscopy and differential scanning calorimetry. Release of 4-MBC from the LMs was found to be slower than its dissolution rate. The influence of the LMs' carrier system on percutaneous penetration was evaluated after their introduction in a model topical formulation (emulsion). In-vitro measurements were performed with cellulose acetate membranes in Franz diffusion cells. The 4-MBC release and diffusion was decreased by 66.7-77.3% with the LM formulation, indicating that the retention capacity of the microparticles was maintained after incorporation into the emulsion. In-vivo human skin penetration of 4-MBC was investigated by tape stripping, a technique for selectively removing the upper cutaneous layers. The amount of sunscreen penetrating into the stratum corneum was greater for the emulsion containing non-encapsulated 4-MBC (36.55% of the applied dose) compared with the formulation with the sunscreen-loaded microparticles (24.57% of the applied dose). The differences between the two formulations were statistically significant in the first (2-4) horny layer strips. Moreover, the LMs' effect measured in-vivo was less pronounced than in-vitro. The increased 4-MBC retention on the skin surface achieved by its incorporation in the LMs should enhance its efficacy and reduce the potential toxicological risk associated with skin penetration
In vivo and in vitro skin permeation of Butyl Methoxydibenzoylmethane from lipospheres
No full textLipospheres loaded with sunscreen BMDBM were prepared and evaluated for skin permeation both in vivo, by tape stripping method, and in vitro, by a flow-through diffusion chamber. The results were found to be predicted by an in vitro methodology involving the diffusion of BMDBM through a lipophilized syntetic membrane into a hydrophilic receptor phase, simulating the viable epidermis better than an ethanolic receptor phase
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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