Luís Antônio Dantas Silva

In vitro skin penetration of clobetasol from lipid nanoparticles: drug extraction and quantitation in different skin layers

Clobetasol propionate (CP) is a potent topical corticosteroid that causes several cutaneous and systemic side effects. In the present work, CP was encapsulated in nanostructured lipid carriers (NLCs) to increase drug retention in the outer skin layers and improve the safety of topical therapy. NLCs were prepared using a microemulsion technique with a mixture of lecithin, taurodeoxycholate, stearic acid, and oleic acid. In vitro penetration studies were performed in a modified Franz-type diffusion cell, and porcine ears were used as a model of human skin. A simple and sensitive liquid chromatographic method was developed and validated for clobetasol determination in different skin layers. NLCs presented uniform size distribution, high zeta potentialand entrapment efficiency values (> 98%). The analytical procedure was validated according to FDA guidelines. Clobetasol recoveries from skin samples were higher than 85%, with no interference of skin components and NLC ingredients. In experiments, after 6 h, a higher drug accumulation in the stratum corneum arising from NLCs compared to aqueous CP solution was observed. Thus, the NLCs demonstrated high potential for targeting CP to the skin and ensuring drug accumulation in the stratum corneum.

Clobetasol‐loaded nanostructured lipid carriers for epidermal targeting

The aim of this study was to investigate in vitro the epidermal targeting potential of clobetasol propionate‐loaded nanostructured lipid carriers (CP‐NLC) when compared to that of chitosan‐coated (CP‐NLC‐C).

Development of carvedilol-cyclodextrin inclusion complexes using fluid-bed granulation: a novel solid-state complexation alternative with technological advantages.

This study sought to evaluate the achievement of carvedilol (CARV) inclusion complexes with modified cyclodextrins (HPβCD and HPγCD) using fluid‐bed granulation (FB).

Preparation of a solid self-microemulsifying drug delivery system by hot-melt extrusion

Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined. The extrudates were then obtained by blending the lipid mixture and HPMCAS using a twin-screw hot-melt extruder. SEM, optical microscopy and PXRD were used to characterize the extrudates. In vitro microemulsion reconstitution and drug release were also studied. L-SMEDDS gave rise to microemulsions with low mean size, PdI and zeta potential (140.04 ± 7.22 nm, 0.219 ± 0.011 and -9.77 ± 0.86 mV). S-SMEDDS were successfully prepared by HME, and an HMPCAS matrix was able to avoid microemulsion reconstitution and retain drug release in pH 1.2 (12.97%-25.54%). Conversely, microemulsion reconstitution and drug release were gradual in pH 6.8 and complete for some formulations. Extrudates prepared at the lowest drug concentration and highest temperature and recirculation time promoted a complete and rapid drug release in pH 6.8 giving rise to small and uniform microemulsion droplets.

Improved tacrolimus skin permeation by co-encapsulation with clobetasol in lipid nanoparticles: Study of drug effects in lipid matrix by electron paramagnetic resonance

Graphical abstract Figure. No Caption available. Abstract Combined therapy with corticosteroids and immunosuppressant‐loaded nanostructured lipid carriers (NLC) could be useful in the treatment of skin diseases. To circumvent NLC loading capacity problems, loaded drugs should have different physicochemical characteristics, such as tacrolimus (TAC) and clobetasol (CLO). Therefore, in the present study, TAC and CLO were encapsulated in NLC (TAC‐NLC, CLO‐NLC and TAC+CLO‐NLC), coated or otherwise with chitosan. Electron paramagnetic resonance (EPR) spectroscopy of different spin labels was used to investigate the impact of drug and oil incorporation on the lipid dynamic behavior of the lipid matrices. In addition, the impact of co‐encapsulation on drug release and skin permeation was evaluated. Entrapment efficiency was greater than 90% for both drugs, even when the maximum drug loading achieved for TAC‐NLC and CLO‐NLC was kept at TAC+CLO‐NLC, because TAC is more soluble in the solid lipid and CLO in the liquid lipid. EPR data indicated that both drugs reduced the lipid fluidity near the polar surface of the lipid matrix, which suggests their presence in this region. In addition, EPR data showed that liquid lipid is also present in more superficial regions of the nanoparticle matrix. CLO was released faster than TAC from TAC+CLO‐NLC, probably because it is more soluble in the liquid lipid. TAC skin penetration was affected by CLO. A 5‐fold increase in TAC penetration was observed from TAC+CLO‐NLC when compared to TAC‐NLC formulations. Coating also increased TAC and CLO permeation to deeper skin layers (1.8‐fold and 1.6‐fold, respectively). TAC+CLO‐NLC seems to be an effective strategy for topical delivery of TAC and CLO, and thus constitutes promising formulations for the treatment of skin diseases.

A Novel Polymer-Lipid Hybrid Nanoparticle For The Improvement Of Topotecan Hydrochloride Physicochemical Properties

BACKGROUND Topotecan (TPT) is a water-soluble derivate of camptothecin, which undergoes ring-opening hydrolysis in neutral solutions, leading to stability loss and poor cellular uptake. Lipid nanoencapsulation can improve TPT stability, and polymer-lipid hybrid nanoparticles (PLN) are interesting alternatives to improve TPT nanoencapsulation. OBJECTIVE This study seeks to prepare complexes between the cationic TPT and the negatively charged dextran sulfate (DS) with a view of improving drug loading, chemical stability and release control. METHODS The optimum ionic molar ratio in DS-TPT complexation was determined, and the selected complex was characterized by FTIR and solid-state 13C NMR. TPT solubility in the free and complexed forms was also assayed. TPT-PLN was then obtained via a microemulsion technique, and particle size, zeta potential, encapsulation efficiency, drug loading and drug recovery were determined. Additionally, the TPT stability and in vitro release were determined from PLN and compared with free TPT, TPT-DS complex and TPT encapsulated in nanostructured lipid carriers (NLC) of similar composition. RESULTS TPT-DS complexation was confirmed by FTIR and NMR. TPT solubility in the complex was drastically decreased when compared to free TPT. TPT-PLN had high encapsulation efficiency (97%) and drug loading capacity (5.5%). Additionally, TPT-PLN showed a mean diameter, polidispersivity index e zeta potential of 140 nm, 0.2 and -22 mV, respectively. The TPT chemical stability and release from PLN were observed to be superior when compared to NLC. CONCLUSION PLN has shown to be a more effective nanosystem for TPT nanoencapsulation because TPT loading, stability and release were superior when compared to TPT-NLC.