Penetration depth,concentration and efficiency of transdermal α-arbutin delivery after ultrasound treatment with albumin-shelled microbubbles in mice

Recently, the feasibility and effects of using microbubbles (MBs) as an ultrasound (US) contrast agent for enhancing the penetration in transdermal delivery in vivo have been demonstrated, but the mechanism and efficiency are unclear. This study demonstrates the penetration depth, concentration and efficiency of transdermal α-arbutin delivery during 4 weeks after US treatment with MBs in mice. Experimental animals were randomly divided into the following four groups (n?=?5 animals per group): (1) penetrating α-arbutin alone (C), (2) US combined with penetrating α-arbutin, (3) US combined with MBs and penetrating α-arbutin, and (4) US combined with diluted MBs and penetrating α-arbutin (UBD). The penetration depths in agarose phantoms and pigskin were 47 and 84% greater for group UBD, respectively, than for group C. The in vitro skin penetration by 2% α-arbutin after 3?h was 83% greater in group UBD than in group C. The degree of in vivo skin whitening (quantified as the luminosity index) in group UBD significantly increased by 25% after 1 week, 34% after 2 weeks, and then stabilized after 3 weeks at 37% in C57BL/6J mice over a 4-week experimental period. Our results indicate that combined treatment with optimal US and MBs can increase skin permeability so as to enhance α-arbutin delivery to inhibit melanogenesis without damaging the skin in mice.     

Hybrid drug delivery system for oropharyngeal,cervical and colorectal cancer – in vitro and in vivo evaluation

The present investigation was designed with the intention to formulate a versatile 5-fluorouracil(5-FU) matrix tablet surpassing issues associated with current conventional chemotherapeutic drug delivery systems. The novel 5-FU matrix tablet fulfills therapeutic needs by engineering matrix tablets utilizing chitosan–sodium alginate interpolyelectrolyte complex (IPEC). IPEC was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The matrix tablets were formulated utilizing IPEC alone and in combination with chitosan, sodium alginate and sodium deoxycholate as permeation enhancer. Pharmaceutical properties, swelling studies, in vitro dissolution and diffusion studies, mucoadhesive studies and in vivo studies were performed for formulated 5-FU. The selected chitosan–sodium alginate IPEC offers pH independent 5-FU release in comparison to alone or physical mixture of chitosan and sodium alginate. Furthermore, novel matrix tablets demonstrated significantly higher bioadhesive properties with controlled 5-FU release without the initial burst effect and also demonstrated a higher permeation of 5-FU. To conclude, the developed novel 5-FU matrix tablets pave way as an excellent alternative for cancer treatment which could potentially minimize the dose dependent side effects and provide better patient compliance.     

Tretinoin or retinol enhancement of lymphokine-activated killer cell proliferation and cytotoxicity against human bladder cancer cells in vitro

目的：研究维Ａ酸（Ｔｒｅ）或维生素Ａ（Ｒｅｔ）对膀胱肿瘤患者淋巴因子激活的杀伤细胞（ＬＡＫ细胞）的增殖和对膀胱肿瘤细胞的细胞毒作用．方法：分别用细胞计数和ＭＴＴ法测定ＬＡＫ细胞的增殖和细胞毒作用．结果：Ｔｒｅ或Ｒｅｔ１０－１００ｎｍｏｌ·Ｌ－１加强由白细胞介素２（ＩＬ２）诱导的ＬＡＫ细胞的增殖和对膀胱肿瘤细胞的杀伤作用．结论：Ｔｒｅ或Ｒｅｔ增强膀胱肿瘤患者ＬＡＫ细胞增殖及对膀胱肿瘤的细胞毒作用．     

Interaction of vascular endothelial cells with leukocytes, platelets and cancer cells in inflammation, thrombosis and cancer growth and metastasis

Adhesion and migration of mammalian cells are of crucial importance in a number of biological events, such as fertilization, embryogenesis, pattern, tissue and organ formation, and in a variety of physiological and pathological processes, including lymphocyte trafficking, leukocyte recruitment, hemostasis, wound healing, tumor angiogenesis and cancer metastasis. All these     

Salmon calcitonin-loaded Eudragit® and Eudragit®-PLGA nanoparticles: in vitro and in vivo evaluation

The main objective of this study was to prepare salmon calcitonin (sCT)-loaded Eudragit®RSPO, Eudragit®L100 and Eudragit®-poly(lactic-co-glycolic acid) blend nanoparticles for in vitro and in vivo evaluation as an oral drug delivery system. The prepared nanoparticles ranged in size from 179.7 to 308.9?nm with a polydispersity index between 0.051 and 2.75, and had surface charges ? ?11 to +6?mV. Efficient sCT encapsulation and release was observed with all the nanoparticle formulations. The polymer type was an important factor that influenced the release characteristics and the in vivo hypocalcemic effect. Nanoparticle formulations were also prepared with sodium taurodeoxycholate (NaTDC) and characterized. No statistically significant difference was noted between the hypocalcemic effect of any of the nanoparticle formulations with and without NaTDC (p?>?0.05). The use of Eudragit®RSPO nanoparticles appears to be a potential approach for the oral delivery of sCT.     

Resveratrol analogue 3,4,4′-trihydroxy-trans-stilbene induces apoptosis and autophagy in human non-small-cell lung cancer cells in vitro

Aim:

To investigate the effects of 3,4,4′-trihydroxy-trans-stilbene (3,4,4′-THS), an analogue of resveratrol, on human non-small-cell lung cancer (NSCLC) cells in vitro.

Methods:

Cell viability of NSCLC A549 cells was determined by MTT assay. Cell apoptosis was evaluated using flow cytometry and TUNEL assay. Cell necrosis was evaluated with LDH assay. The expression of apoptosis- or autophagy-associated proteins was measured using Western blotting. The formation of acidic compartments was detected using AO staining, neutral red staining and Lysotracker-Red staining. LC3 punctae were analyzed with fluorescence microscopy.

Results:

Treatment with 3,4,4′-THS (10-80 μmol/L) concentration-dependently inhibited the cell viability. It did not cause cell necrosis, but induced apoptosis accompanied by up-regulation of cleavaged PARP, caspase3/9 and Bax, and by down-regulation of Bcl-2 and surviving. It also increased the formation of acidic compartments, LC3-II accumulation and GFP-LC3 labeled autophagosomes in the cells. It inhibited the mTOR-dependent pathway, but did not impair autophagic flux. 3,4,4′-THS-induced cell death was enhanced by the autophagy inhibitors 3-MA (5 mmol/L) or Wortmannin (2 μmol/L). Moreover, 3,4,4′-THS treatment elevated the ROS levels in the cells, and co-treatment with 3-MA further elevated the ROS levels. 3,4,4′-THS-induced apoptosis and autophagy in the cells was attenuated by NAC (10 mmol/L)

Conclusion:

3,4,4′-THS induces both apoptosis and autophagy in NSCLC A549 cells in vitro. Autophagy inhibitors promote 3,4,4′-THS-induced apoptosis of A549 cells, thus combination of 3,4,4′-THS and autophagy inhibitor provides a promising strategy for NSCLC treatment.     

Salmon calcitonin-loaded Eudragit® and Eudragit®-PLGA nanoparticles: in vitro and in vivo evaluation

The main objective of this study was to prepare salmon calcitonin (sCT)-loaded Eudragit?RSPO, Eudragit?L100 and Eudragit?-poly(lactic-co-glycolic acid) blend nanoparticles for in vitro and in vivo evaluation as an oral drug delivery system. The prepared nanoparticles ranged in size from 179.7 to 308.9?nm with a polydispersity index between 0.051 and 2.75, and had surface charges ~ -11 to +6?mV. Efficient sCT encapsulation and release was observed with all the nanoparticle formulations. The polymer type was an important factor that influenced the release characteristics and the in vivo hypocalcemic effect. Nanoparticle formulations were also prepared with sodium taurodeoxycholate (NaTDC) and characterized. No statistically significant difference was noted between the hypocalcemic effect of any of the nanoparticle formulations with and without NaTDC (p?>?0.05). The use of Eudragit?RSPO nanoparticles appears to be a potential approach for the oral delivery of sCT.     

Hydrogen sulfide-releasing aspirin suppresses NF-κB signaling in estrogen receptor negative breast cancer cells in vitro and in vivo

Hormone-dependent estrogen receptor positive (ER+) breast cancers generally respond well to anti-estrogen therapy. Unfortunately, hormone-independent estrogen receptor negative (ER-) breast cancers are aggressive, respond poorly to current treatments and have a poor prognosis. New approaches and targets are needed for the prevention and treatment of ER- breast cancer. The NF-κB signaling pathway is strongly implicated in ER- tumor genesis, constituting a possible target for treatment. Hydrogen sulfide-releasing aspirin (HS-ASA), a novel and safer derivative of aspirin, has shown promise as an anti-cancer agent. We examined the growth inhibitory effect of HS-ASA via alterations in cell proliferation, cell cycle phase transitions, and apoptosis, using MDA-MB-231 cells as a model of triple negative breast cancer. Tumor xenografts in mice, representing human ER- breast cancer, were evaluated for reduction in tumor size, followed by immunohistochemical analysis for proliferation, apoptosis and expression of NF-κB. HS-ASA suppressed the growth of MDA-MB-231 cells by induction of G(0)/G(1) arrest and apoptosis, down-regulation of NF-κB, reduction of thioredoxin reductase activity, and increased levels reactive oxygen species. Tumor xenografts in mice, were significantly reduced in volume and mass by HS-ASA treatment. The decrease in tumor mass was associated with inhibition of cell proliferation, induction of apoptosis and decrease in NF-κB levels in vivo. HS-ASA has anti-cancer potential against ER- breast cancer and merits further study.     

PPAR-γ ligand promotes the growth of APC-mutated HT-29 human colon cancer cells in vitro and in vivo

Summary PPAR-γ has been known to induce suppression, differentiation and reversal of malignant changes in colon cancer in vitro. However, there are several reports that PPAR-γ ligands enhance colon polyp development in APC^min mice in vivo. These contradictory results have not yet been thoroughly explained. To explain the contradictory results, we analyzed the effects of different concentrations of the PPAR-γ agonist, 15-deoxy-D12, 14-prostaglandin (15-d Δ PGJ2) and pioglitazone, on APC gene-mutated colon cancer cell lines (HT-29). We measured cell growth and suppression by cell count and MTT assay and analyzed the expression of β-catenin and c-Myc protein by Western blot. In addition, we inoculated HT-29 cells into APC^min mice to compare tumor size. High concentrations (10–100 μM/L 15-d Δ PGJ2 and pioglitazone) of PPAR-γ ligand suppressed growth, while low concentrations (0.01–1 μM/L 15-d Δ PGJ2 and pioglitazone) of PPAR-γ ligand promoted growth. In particular, the effects of 0.1 μM/L 15-d Δ PGJ2 and pioglitazone on cell growth were statistically significant (P = 0.003, P = 0.001, respectively). Tumor growth was associated with an increase in β-catenin and c-Myc expression. The growth of xenograft tumors was greater in PPAR-γ ligand-treated mice than in control mice (control vs day 14: P = 0.024, control vs day 28: P = 0.007). The expression of β-catenin and c-Myc protein were also elevated in PPAR-γ-treated mouse tissues. PPAR-γ ligand can promote the growth of APC-mutated HT-29 colon cancer cells in vitro and in vivo. In addition, the tumor promoting effect seems to be associated with an increase in β-catenin and c-Myc expression. We think that well-controlled clinical trials should be conducted to confirm our results and to verify clinical applications.     

A local drug delivery system based on visible light-cured glycol chitosan and doxorubicin⋅hydrochloride for thyroid cancer treatment in vitro and in vivo

Systemic drug delivery systems (SDDSs) for thyroid cancer treatment are associated with serious side effects including nausea, anorexia, and hair loss as a result of damage to normal tissues. In this study, we investigated the feasibility of a local DDS (LDDS) based on visible light-cured glycol chitosan (GC) hydrogel and doxorubicin?hydrochloride (DOX?HCl), called GC10/DOX, on thyroid cancer treatment in vivo. Visible light irradiation increased the storage modulus and swelling ratio of the GC10/DOX hydrogel precursor. The release of DOX?HCl from GC10/DOX exhibited two unique patterns comprising an initial burst within 18?hours, followed by a controlled and sustained release thereafter. In vitro cell viability testing showed that GC10/DOX had a greater antitumor effect than free DOX?HCl and GC10 hydrogel controls. In vivo, local injection of GC10/DOX near tumor tissue led to a superior antitumor effect compared with controls consisting of free DOX?HCl intravenously injected to the tail vein of thyroid cancer-bearing mouse and GC10 hydrogel subcutaneously injected near the tumor. Altogether, our results suggest that GC10/DOX may have clinical potential for thyroid cancer treatment.     

Cell cycle kinetics responses of human stomach cancer cells to reduction in polyamine levels by treatment with αDifluoromethylornithine in vitro

Treatment of human gastric cancer clones in vitro with low doses of DFMO (5 mM) produced elongation of the cell population doubling times and lowering of the saturation densities. By contrast, DFMO treatment of normal human skin fibroblasts altered only the saturation density. The lack of an effect of 5 mM DFMO on the doubling time of normal fibroblasts may be directly related to baseline intracellular putrescine levels, which were about 2.5 times higher than in the cancer cells. The same dose of DFMO caused a rapid decrease in intracellular polyamine levels in the tumor clones. The effects on the doubling time and saturation density were almost totally abolished by the addition of 50 M putrescine to the growth medium during the first 24 h of treatment with DFMO. Exposure to 5 mM DFMO for 24 h caused the human gastric cancer cells to become blocked in G₁ phase only, and this led to a reduction in the fraction of cells in S phase. The G₁ block was reversible and this cohort of cells eventually passed through S phase and then through G₂ and M.A higher 100 mM dose of DFMO and longer exposure times for both doses produced cell cycle changes and death of more than 90% of the cell population. These data suggest that cell kinetics changes observed under these experimental conditions may reflect polyamine-related alterations in the biochemical events of cell cycle progression kinetics; but may also be the result of DFMO-induced loss of cell viability.Abbreviations DFMO -Difluoromethylornithine - ODC ornithine decarboxylase - ARA C cytosine arabinosidede - MGBG methylglyoxal bis(guanylhydrazone)     

Involvement of Ca²⁺ and ATP in enhanced gene delivery by bubble liposomes and ultrasound exposure

Recently, we reported the accelerated gene transfection efficiency of laminin-derived AG73-peptide-labeled polyethylene glycol-modified liposomes (AG73-PEG liposomes) and cell penetrating TAT-peptide labeled PEG liposomes using PEG-modified liposomes, which trap echo-contrast gas, "Bubble liposomes" (BLs), and ultrasound (US) exposure. BLs and US exposure were reported to enhance the endosomal escape of AG73-PEG liposomes, thereby leading to increased gene expression. However, the mechanism behind the effect of BLs and US exposure on endosomes is not well understood. US exposure was reported to induce an influx of calcium ions (Ca2?) by enhancing permeability of the cell membrane. Therefore, we examined the effect of Ca2? on the endosomal escape and transfection efficiency of AG73-PEG liposomes, which were previously enhanced by BLs and US exposure. For cells treated with EGTA, the endosomal escape and gene expression of AG73-PEG liposomes were not enhanced by BLs and US exposure. Similarly, transfection efficiency of the AG73-PEG liposomes in ATP-depleted cells was not enhanced. Our results suggest that Ca2? and ATP are necessary for the enhanced endosomal escape and gene expression of AG73-PEG liposomes by BLs and US exposure. These findings may contribute to the development of useful techniques to improve endosomal escape and achieve efficient gene transfection.     

Targeted delivery of doxorubicin through conjugation with EGF receptor–binding peptide overcomes drug resistance in human colon cancer cells

Background and Purpose

Induction of multidrug resistance by doxorubicin (DOX), together with non-specific toxicities, has restricted DOX-based chemotherapy. Recently, we demonstrated that DOX conjugated with an EGF receptor-binding peptide (DOX-EBP) had enhanced anticancer efficacy and reduced systemic toxicity when targeting EGF receptor-overexpressing tumours. Here we investigated whether DOX-EBP is able to overcome drug resistance and the underlying molecular mechanisms.

Experimental Approach

DOX-resistant SW480/DOX cells were derived from non-resistant SW480 cells by stepwise exposure to increasing concentrations of DOX, and P-glycoprotein overexpression induced by DOX was confirmed by Western blotting. Cytotoxicity and intracellular distribution of drugs were evaluated by MTT assay and fluorescence microscopy respectively. EGF receptor-mediated endocytosis was determined in EGF receptor and endocytosis inhibition assays. Drug accumulation in tumour cells and murine xenografts was determined by HPLC.

Key Results

The cytotoxicity and accumulation of DOX-EBP in SW480/DOX cells were almost the same as in SW480 cells, but those of free DOX were reduced. DOX-EBP accumulation was prevented by inhibitors of both EGF receptors and endocytosis, suggesting EGF receptors mediate endocytotic uptake. Tumour accumulation of DOX-EBP was significantly higher than free DOX in mice, and the levels of DOX-EBP were similar in DOX-resistant and non-resistant tumour tissues. Importantly, DOX-EBP, but not free DOX, was effective at inhibiting solid tumour growth and increased survival rate in both sensitive and resistant models.

Conclusion and Implications

DOX-EBP can overcome DOX resistance of tumour cells and increase in vivo antitumour efficacy. Therefore, it has the potential to be a potent therapeutic agent for treating drug-resistant cancers.     

Plumbagin inhibits cell growth and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway

Aim:

To investigate the effects and underlying mechanisms of plumbagin, a naphthoquinone derived from medicinal plant Plumbago zeylanica, on human gastric cancer (GC) cells.

Methods:

Human gastric cancer cell lines SGC-7901, MKN-28, and AGS were used. The cell viability was examined using CCK-8 viability assay. Cell proliferation rate was determined using both clonogenic assay and EdU incorporation assay. Apoptosis was detected via Annexin V/propidium iodide double-labeled flow cytometry. Western blotting was used to assess the expression of both NF-κB-regulated gene products and TNF-α-induced activation of p65, IκBα, and IKK. The intracellular location of NF-κB p65 was detected using confocal microscopy.

Results:

Plumbagin (2.5–40 μmol/L) concentration-dependently reduced the viability of the GC cells. The IC₅₀ value of plumbagin in SGC-7901, MKN-28, and AGS cells was 19.12, 13.64, and 10.12 μmol/L, respectively. The compound (5–20 μmol/L) concentration-dependently induced apoptosis of SGC-7901 cells, and potentiated the sensitivity of SGC-7901 cells to chemotherapeutic agents TNF-αand cisplatin. The compound (10 μmol/L) downregulated the expression of NF-κB-regulated gene products, including IAP1, XIAP, Bcl-2, Bcl-xL, tumor factor (TF), and VEGF. In addition to inhibition of NF-κB p65 nuclear translocation, the compound also suppressed TNF-α-induced phosphorylation of p65 and IKK, and the degradation of IκBα.

Conclusion:

Plumbagin inhibits cell growth and potentiates apoptosis in human GC cells through the NF-κB pathway.     

α-Hederin inhibits growth of lung cancer A549 cells in vitro and in vivo by decreasing c-Myc and HIF-1α dependent glycolysis

OBJECTIVE α-Hederin is an effective component of the traditional Chinese medicine Pulsatilla chinensis,which has been reported to exert many pharmacological activities. However, the effect of α-hederin on metabolism is still unclear. This study aimed to illuminate the role of α-hederin in glucose metabolism in lung cancer cells and investigate the molecular mechanism of α-hederin. METHODS CCK8 and colony formation assays were employed to assess the anti-proliferative effects induced by α-hederin. Glucose uptake, ATP generation, and reduced lactate production were measured using kits, and an A549 tumor xenograft mouse model of lung cancer was used to assess the in vivo antitumor effect of α-hederin(5, 10 mg·kg~(-1)). Glycolytic-related key enzymes were detected by Western blotting and immunohistochemical staining. RESULTS Cell proliferation was significantly inhibited by α-hederin in a dose-dependent manner and that α-hederin inhibited glucose uptake and ATP generation and reduced lactate production. Furthermore, α-hederin remarkably inhibited hexokinase 2(HK2), glucose transporters 1(GLUT1), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), monocarboxylate transporter(MCT4), c-Myc, and hypoxia inducible factor-1α(HIF-1α) protein expression. Using inhibitors, we proved that α-hederin inhibits glycolysis by inhibiting glycolytic regulators. Moreover, a tumor xenograft mouse model of lung cancer further confirmed that α-hederin inhibits lung cancer growth via inhibiting glycolysisin vivo. CONCLUSION α-Hederin inhibits the growth of non-small cell lung cancer A549 cells by inhibiting glycolysis.The mechanism of glycolysis inhibition includes α-hederin inhibiting the expression of the glycolytic regulatory factors HIF-1α and c-Myc.     

Galectin-3 gene silencing inhibits migration and invasion of human tongue cancer cells in vitro via downregulating β-catenin

Aim:

Galectin-3 (Gal-3) is a member of the carbohydrate-binding protein family that contributes to neoplastic transformation, tumor survival, angiogenesis, and metastasis. The aim of this study is to investigate the role of Gal-3 in human tongue cancer progression.

Methods:

Human tongue cancer cell lines (SCC-4 and CAL27) were transfected with a small-interfering RNA against Gal-3 (Gal-3-siRNA). The migration and invasion of the cells were examined using a scratch assay and BD BioCoat Matrigel Invasion Chamber, respectively. The mRNA and protein levels of β-catenin, Akt/pAkt, GSK-3β/pGSK-3β, MMP-9 in the cells were measured using RT-PCR and Western blotting, respectively.

Results:

Transient silencing of Gal-3 gene for 48 h significantly suppressed the migration and invasion of both SCC-4 and CAL27 cells. Silencing of Gal-3 gene significantly decreased the protein level of β-catenin, leaving the mRNA level of β-catenin unaffected. Furthermore, silencing Gal-3 gene significantly decreased the levels of phosphorylated Akt and GSK-3β, and suppressed the mRNA and protein levels of MMP-9 in the cells.

Conclusion:

Our data suggest that Gal-3 mediates the migration and invasion of tongue cancer cells in vitro via regulating the Wnt/β-catenin signaling pathway and Akt phosphorylation.     

Preparation and in vitro–in vivo evaluation of Witepsol® H35 based self-nanoemulsifying drug delivery systems (SNEDDS) of coenzyme Q10

Coenzyme Q₁₀ (CoQ₁₀) was formulated into self-nanoemulsifying drug delivery systems (SNEDDS) to overcome low bioavailability attributed to hydrophobic nature of the drug. Screening of oil phase, surfactants and co-surfactants were performed to select Witepsol^® H35, Solutol^® HS15 and Lauroglycol^® FCC, respectively. Ternary phase diagrams were drawn to identify nanoemulsifying region followed by optimization of SNEDDS formulation. The optimized formulation, CoQ₁₀, Witepsol^® H35, Solutol^® HS15 and Lauroglycol^® FCC in the weight ratio of 1:0.7:4:2, respectively, emulsified readily at 37 °C with mean emulsion droplet size of 32.4 nm. The stability test of the optimized formulation in pH 1.2 and 6.8 buffers confirmed no pH effect on emulsion droplet size. In vitro dissolution (emulsification) test and in vivo animal study of the formulation elucidated the complete emulsification of drug and improved oral bioavailability of poorly soluble CoQ₁₀.     

Enhancement of felodipine dissolution rate through its incorporation into Eudragit® E-PHB polymeric microparticles: in vitro characterization and investigation of absorption in rats

In this study, felodipine was incorporated into microparticles prepared with Eudragit? E and it blended with poly(3-hydroxybutyrate) (PHB) using the emulsion-solvent evaporation technique, with the aim of improving the dissolution rate of the drug. The formulation prepared with Eudragit? E showed irregular and fragmented microparticles, with a loading efficiency (LE) of 82.6%. When the microparticles were prepared with a blend of Eudragit? E and PHB, they had a spherical form with a LE of 103.9%. X-ray diffraction and differential thermal analysis indicated a reduction in the crystallinity of felodipine after its incorporation into the microparticles, which caused a significant increase in the felodipine dissolution rate. An investigation into the absorption in rats was carried out using high-performance liquid chromatography analysis of the blood collected 20 and 60 min after the animals were administered felodipine [30 mg/Kg, orally (p.o.)] or felodipine microparticles (30 mg/Kg, p.o.). Animals that were given felodipine showed mean plasmatic levels of 0.0125 (±0.00156) and 0.0240 (±0.0069) μg mL(-1) after 20 and 60 min, respectively, whereas animals that received microparticles containing felodipine showed respective mean plasmatic levels of 0.0651 (±0.0120) and 0.0369 (±0.0145) μg mL(-1) . Our data suggest that the incorporation into microparticles significantly enhanced the release of felodipine, improving its absorption in rats.