Solid Inclusion Complexes Research Articles

Spectroscopic study and antioxidant properties of the inclusion complexes of rosmarinic acid with natural and derivative cyclodextrins

Measurement of total antioxidant activity/capacity of polyphenols in various solvent media necessitates the use of cyclodextrins to solubilize lipophilic antioxidants of poor aqueous solubility. The inclusion complexes of the slightly water soluble antioxidant, rosmarinic acid (RA), with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxyethyl-β-cyclodextrin (HE-β-CD), and methyl-β-cyclodextrin (M-β-CD) were investigated for the first time. The effect of cyclodextrins (CDs) on the spectral features of RA was measured in aqueous medium using UV–vis and steady-state fluorescence techniques by varying the concentrations of CDs. The molar stoichiometry of RA–CD inclusion complexes was verified as 1:1, and the formation constants of the complexes were determined from Benesi–Hildebrand equation using fluorescence spectroscopic data. Among the CDs, maximum inclusion ability was measured in the case of M-β-CD followed by HP-β-CD, HE-β-CD, β-CD and α-CD. Solid inclusion complexes were prepared by freeze drying, and their functional groups were analyzed by IR spectroscopy. Antioxidant capacity of CD-complexed rosmarinic acid was measured to be higher than that of the lone hydroxycinnamic acid by the CUPric Reducing Antioxidant Capacity (CUPRAC) method. The mechanism of the TAC increase was interpreted as the stabilization of the 1 − e oxidized o-catechol moiety of RA by enhanced intramolecular H-bonding in a hydrophobic environment provided by CDs, mostly by M-β-CD.

Improvement of some pharmaceutical properties of mycophenolate mofetil (MMF) by para sulphonatocalix[4]resorcinarene inclusion complex

As a part of our investigations to unfold the chemistry of calixresorcinarene, we have focused on the formation of inclusion complex of a poorly soluble (43 μg ml−1 at pH 7) drug mycophenolate mofetil (MMF) an immunosuppressive agent and an inosine monophosphate dehydrogenase (IMPDH) inhibitor with para sulphonatocalix[4]resorcinarene (PSC4R). The complete complexation of the drug was achieved after 48 h of stirring with para sulphonatocalix[4]resorcinarene(PSC[4]R) in water and evaporation of water yield the solid complex. The interaction between para sulphonatocalix[4]resorcinarene(PSC[4]R) and MMF in solid state inclusion complexes was accomplished by aqueous phase solubility studies, Thermal Analysis, HPLC, PXRD, FT-IR, and UV–Vis spectroscopy. The results of the phase solubility experiments are in good conformity to signify the formation of 2:1 PSC4R: MMF complexes. The purpose of this study was to enhance solubility and resulting in high dissolution rate and bioavailability of this essentially water insoluble drug. The results of the in vivo study shows that there is a remarkable change in the toxicity of the pure drug MMF and complex did not produce any mortality up to 2200 mg kg−1.

Improvement of solubility and dissolution properties of clotrimazole by solid dispersions and inclusion complexes

Solid dispersions of a slightly water-soluble drug, clotrimazole, were prepared in different weight ratios using polyethyleneglycol 4000 and different molecular weight polyvinyl pyrrolidones as carriers. Moreover, binary and ternary β-cyclodextrin complexes were prepared in different molar ratios. Both solid dispersions and β-cyclodextrin complexes were prepared by solvent evaporation technique. A phase solubility method was used to evaluate the effect of the tested carriers on the aqueous solubility of clotrimazole. The dissolution of all the preparations was tested using the USP paddle method. The selected solid dispersions and inclusion complexes were characterized by differential scanning calorimetry and X-ray powder diffractometry studies, and results clarified the role of the tested carriers in decreasing the crystallinity of clotrimazole and complexing abilities. Based on physical characters and in vitro drug release pattern, polyvinylpyrrolidone solid dispersions (1:1 weight ratio) and ternary cyclodextrin complexes (clotrimazole-β-cyclodextrin complexes with either polymer, 1:1 molar ratio) were selected as ideal batches for suppositories. Suppocire AM/50 mg carbopol 940, was chosen as a suppository base and the suppositories were prepared by molding technique. The prepared suppositories were characterized for weight variation, softening time and drug content. All these properties were found to be ideal. The in vitro drug release pattern was determined in citrate buffer (pH 4.5) containing 1% sodium lauryl sulfate. The in vitro release of clotrimazole from its solid dispersions and inclusion complexes incorporated suppositories was markedly improved when compared to the intact drug incorporated suppositories. Polyvinyl pyrrolidone solid dispersions incorporated suppositories were found to possess excellent antifungal activity.

Study of inclusion complex of β-cyclodextrin and Ortho-Anisidine; photophysical and electrochemical behaviors

Effect of solvents, buffer solutions of different pH and β-cyclodextrin on the absorption spectra of Ortho-Anisidine ( O- AN) have been investigated. The host–guest inclusion complexation between β-CD and O- AN were investigated by spectrophotometric (UV–Visible) and electrochemical (CV) methods. The UV–Visible and CV studies indicated the β-CD forms 1:1 inclusion complex with O- AN. In electrochemical studies the anodic peak current ( i pa) decreased drastically with increasing β-CD and the anodic peak potential ( E pa) shifted in positive direction. These result also evidence for the formation of inclusion complex between β-CD and O- AN. A mechanism is proposed to explain the inclusion complex. The inclusion interaction was examined and the thermodynamic parameters (ΔG, ΔH and ΔS) of inclusion process are also determined. The experimental results indicated that the inclusion process is an exergonic and spontaneous process. Stable solid inclusion complex were prepared and characterized by FT-IR, Scanning Electron Microscopy (SEM) and X-ray diffraction and docking studies by RasMol tool methods.

Physicochemical characterization of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions, and finasteride: β-cyclodextrin inclusion complexes

Finasteride is a practically insoluble in water drug that belongs to the Class II of the BCS (poor solubility and high permeability). Solid dispersions are solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. Solid dispersions are a successful strategy to improve drug release of poorly water-soluble drugs such as finasteride. Natural cyclodextrins are doughnut-shaped molecules with an internal hydrophobic cavity and a hydrophilic external surface. The lipophilic cavity enables cyclodextrins to form non-covalent inclusion complexes with a wide variety of poorly water-soluble drugs such as finasteride. The aim of this study was to investigate the formation of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions and finasteride:β-cyclodextrin inclusion complexes by solvent evaporation method using a mixture of water:ethanol (1:1). The formation of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions and finasteride:β-cyclodextrin inclusion complexes was investigated and characterized by differential scanning calorimetry (DSC), infrared (IR) spectroscopy, and dissolution studies from capsules containing a quantity equivalent to 5 mg of finasteride. The DSC thermograms revealed the transformation of finasteride into the amorphous state in solid dispersions with PEG 6000 and Kollidon K25, and in inclusion complexes with β-cyclodextrin. The IR spectra demonstrated molecular interaction in solid dispersions of finasteride with PEG 6000, and in inclusion complexes with β-cyclodextrin. Dissolution rate of solid dispersions and inclusion complexes was significantly greater than that of corresponding physical mixtures and pure drug, indicating that the formation of solid dispersions and inclusion complexes increased the solubility of the poorly soluble drug, finasteride.

Chiral recognition and complexation behaviour of β-CyD vs. l- and dl-serine by FTIR-ATR spectroscopy

Solid inclusion complexes of the amino acid ( d, l)-serine and ( l)-serine with β-cyclodextrin (β-CD) have been investigated by Fourier transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR), in order to put into evidence the effects of chiral properties on the complexation process. The spectral changes induced by complexation in the vibrational spectra of serine have been monitored in the 600–4000 cm −1 range, recognizing the functional groups taking part in the “host–guest” interactions. Again, the quantitative analysis, vs. T, of the C O stretching vibration, by means of a best-fit procedure, furnished the enthalpy changes associated to the binding of serine with β-CD in solid phase. The most stable inclusion complex turned out to be the one formed by ( l)-serine, and then ( d, l)-serine.

Fluorescence enhancement of rhodamine 6G by forming inclusion complexes with β-cyclodextrin

That association by partial inclusion occurs in the complexes of β-cyclodextrin and rhodamine 6G was found in a spectrofluorescence study of the interaction of rhodamine 6G (Rh6G) and β-cyclodextrin (β-CD) made mixing them. Fluorescence of Rh6G is generally enhanced, in complexes of Rh6G and β-cyclodextrin in aqueous solutions. The solid inclusion complex of Rh6G and β-CD has been studied by Ultraviolet (UV) spectroscopy, Fluorimetry, Fourier Transform Infrared (FTIR), 1H Nuclear Magnetic Resonance ( 1HNMR) and in the Scanning Electron Microscope (SEM). The change in free energy, ΔG of the inclusion process was sought to be determined for the ground state as ΔGg = 15.3 in water, 14.8 in DMF, 15.5 in DMSO and for the excited state as ΔGe = 25.5 in water, 23.7 in DMF and 24.9 in DMSO. Interaction studies of Rh6G and β-CD in the solvents, water, DMF and DMSO confirm the presence of intra-molecular charge transfer (ICT) in Rh6G. Changes in the absorption and emission spectra by H-bond formation and the equilibrium of the H-bonded complexes have been studied in both ground and excited states. Shift to longer wavelengths and difference in absorption and fluorescence intensities were observed in the absorption and emission spectra.

Preparation and characterization of inclusion complexes of antitumor camptothecin with cucurbit[n = 7, 8]urils

The slightly water-soluble anticancer drug camptothecin (CPT) and its inclusion complexes with cucurbit[n = 7, 8]uril (Q[n] (n = 7, 8)) were investigated. The formation of 1:2 complexes with Q[n] (n = 7, 8) in aqueous solution was confirmed by fluorescence spectroscopy and the apparent stability constants were determined to be higher than 3.01 × 1012 L2/mol2. The solid inclusion complexes of CPT and Q[n] (n = 7, 8) were also prepared by the co-evaporation method and characterized by Fourier transformation-infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Aqueous solubility and dissolution studies indicate that the complexes exhibited significantly increased dissolution rates compared with the pure drug and physical mixtures. The potential of Q[7] or Q[8] for stabilizing lactone modality of CPT was investigated by the High Performance Liquid Chromatography (HPLC) method. The results reveal more than 63% CPT lactone form (active form) in CPT-Q[7] or Q[8] complexes compared to only 36% CPT lactone form in the absence of Q[7] or Q[8] after being incubated in the phosphate buffer solution (pH 7.4 at 37°C) for 5 h.

Preparation, quantitive analysis and bacteriostasis of solid state iodine inclusion complex with β-cyclodextrin

A solid state iodine/β-cyclodextrin inclusion complex (iodine/β-CD) was prepared by the saturated water solution method. The iodine/β-CD binding constant was 1,286 M−1 and the stoichiometric ratio was 1:1(I2: β-CD). In order to determine the iodine content in the complex powder, a novel iodimetry method was investigated, and its accuracy and expeditiousness were verified by high performance liquid chromatography (HPLC). Release behaviors of iodine/β-CD powder were investigated by iodimetry and thermogravimetric (TG) analyzer respectively. The loss percentage of iodine was 5.8wt% for 7 days exposing under room temperature, and a time versus release curve was established. The TG diagram not only proved the stability of I2 in the iodine/β-CD complex, but also clarified the thermal decomposition behavior of the iodine/β-CD. For verifying the germicidal activity of iodine encapsulated by β-CD, the Aspergillus niger, a kind of common fungus in the food, was taken as an evaluation media. The results indicate that by the method of disc diffusion, the discs with 1.5wt% iodine showed an obvious bacteriostasis effect for Aspergillus niger.

Temperature Effect on the Vibrational Dynamics of Cyclodextrin Inclusion Complexes: Investigation by FTIR-ATR Spectroscopy and Numerical Simulation

The vibrational dynamics of solid inclusion complexes of the nonsteroidal anti-inflammatory drug Ibuprofen (IBP) with beta-cyclodextrin (beta-CD) and methyl-beta-cyclodextrin (Me-beta-CD) has been investigated by using attenuated total reflection-Fourier transform infrared FTIR-ATR spectroscopy, in order to monitor the changes induced, as a consequence of complexation, on the vibrational spectrum of IBP, in the wavenumber range 600-4000 cm(-1). Quantum chemical calculations were performed on monomeric and dimeric structures of IBP, derived from symmetric hydrogen bonding of the two carboxylic groups, in order to unambiguously assign some characteristic IR bands in the IBP spectrum. The evolution in temperature from 250 to 340 K of the C horizontal lineO stretching vibration, described by a best-fit procedure, allowed us to extract the thermodynamic parameter DeltaH associated to the binding of IBP with betaCDs in the solid phase. By comparing these results, Me-beta-CD has been shown to be the most effective carrier for IBP.

Inclusion complex of α-lipoic acid and modified cyclodextrins

The solubility of α-lipoic acid (LA) with the addition of modified cyclodextrins was investigated using the solubility method. The solubility of LA in the presence of β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), mono-6-O-glucopyranosyl-β-cyclodextrin (mono-G1-β-CD), methyl-β-cyclodextrin (Me-β-CD), 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD), and sulfobutylether-β-cyclodextrin (SBE-β-CD) was higher than that of LA itself. In particular, the solubility of LA in the presence of SBE-β-CD was 20 times higher than that of LA alone. The structure of the inclusion complex of SBE-β-CD and LA in aqueous solution was examined by 1H-1H ROESY NMR spectroscopy. The 1,2-dithiolane moiety of LA was included from the secondary hydroxyl face of SBE-β-CD. The solid complexes of LA and SBE-β-CD were prepared by the kneading and freeze-drying methods. Formation of the solid complexes was confirmed by X-ray diffraction patterns (XRD), differential scanning calorimetry (DSC), and infrared spectroscopy (IR). The kneading and freeze-drying methods were successful for obtaining the solid inclusion complexes with improved thermal stability.

Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique

The solid-state properties and dissolution behaviour of lamotrigine in its inclusion complex with beta-cyclodextrin (betaCD) and solid dispersions with polyvinylpyrrolidone K30 (PVP K30) and polyethyleneglycol 6000 were investigated. The phase solubility profile of lamotrigine with betaCD was classified as AL-type, indicating formation of a 1:1 stoichiometry inclusion complex, with a stability constant of 369.96+/-2.26 M(-1). Solvent evaporation and kneading methods were used to prepare solid dispersions and inclusion complexes, respectively. The interaction of lamotrigine with these hydrophilic carriers was evaluated by powder X-ray diffractometry, Fourier transform infrared spectroscopy and differential scanning calorimetry. These studies revealed that the drug was no longer present in crystalline state but was converted to an amorphous form. Among the binary systems tested, PVP K30 (1:5) showed greatest enhancement of the solubility and dissolution of lamotrigine.

Decreased B16F10 melanoma growth and impaired tumour vascularization in BDF1 mice with quercetin-cyclodextrin binary system

The aim of this work was to study the inclusion behaviour of a poorly water-soluble bioflavonoid, quercetin, towards sulfobutyl ether-7beta-cyclodextrin. It also involves angiogenesis inhibition in-vivo in addition to in-vitro human cancer cell growth inhibition study of quercetin and its cyclodextrin complex. Drug-cyclodextrin solid inclusion complexes were prepared and characterized in solution and in the solid state. An in-vitro anti-proliferation study using plain drug and its solubilized form was carried out on human cancer cell lines of different origin. Further, an in-vivo tumour growth inhibition study was carried out using a mouse melanoma model. Histological sections of tumours were examined for the evaluation of tumour microvessel density. Significant enhancement of the solubility and dissolution rate of the quercetin, which occurred after complexation, might be attributed to the decrease in crystallinity of drug. SBE7betaCD complex of quercetin was more potent for inhibiting cell proliferation in human erythroleukaemia and cervix cancer cells. Decreased tumour microvessel density in mouse melanoma after oral quercetin administration led to diminished tumour cell proliferation. Quercetin-SBE7betaCD complex showed significantly improved anti-cancer activity at much lower concentration than the plain drug, providing evidence for dose reduction without affecting therapeutic efficacy when using cyclodextrin carriers.

T-dependence of the vibrational dynamics of IBP/diME-β-CD in solid state: A FT-IR spectral and quantum chemical study

Solid inclusion complex of the non-steroidal anti-inflammatory drug Ibuprofen (IBP, (2-[4-(2-methylpropyl)phenyl]-propanoic acid) with (2,6-dimethyl)-β-cyclodextrin (diME-β-CD) has been investigated by Fourier transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR spectroscopy) and numerical simulation. The complexation-induced changes in the FTIR-ATR spectrum of IBP have been interpreted by comparison with the theoretical vibrational wavenumbers and IR intensities of dimeric structures of IBP, derived from symmetric hydrogen bonding of the two carboxylic groups, computed by using Density Functional Theory (DFT) calculations. From temperature-dependent studies, the enthalpy change Δ H associated with the binding of IBP with diME-β-CD for 1:1 stoichiometry, in solid phase, has been estimated.

Solid state characterization of domperidone: Hydroxypropyl-b-cyclodextrin inclusion complex

The purpose of the present study was to prepare inclusion complex of domperidone with hydroxylpropyl-β-cyclodextrin in order improved the solubility and hence to increase dissolution of domperidone. An effect of concentration of hydroxylpropyl-β-cyclodextrin on the aqueous solubility of domperidone was determined by phase-solubility method. The aqueous solubility of domperidone increased as a function of hydroxylpropyl-β-cyclodextrin concentration, showing AL type diagram. Solid domperidone/hydroxylpropyl-β-cyclodextrin complex was prepared in ratio 1:1 by ultrasonication and kneading method. Solid state inclusion complex was characterized by FTIR, powder X-ray diffraction and differential-scanning calorimetry techniques. FTIR studies showed intactness of drug in complex whereas powder diffraction studies showed that hydroxylpropyl-β-cyclodextrin complex was amorphous. Solubility studies showed that complexation increased domperidone solubility as compared to pure drug in 0.1M hydrochloric acid and distilled water. Drug content confirms that ultrasonication is one of the efficient methods to prepare inclusion complex. Dissolution data of inclusion complexes also indicated that there is 1.4 folds increase in dissolution as compared to pure drug and was observed in case of inclusion complexes prepared by ultrasonication.

Study of the complexation behaviour of fexofenadine with β-cyclodextrin

Fexofenadine is a selective histamine H1 receptor antagonist, used for relief of the symptoms of allergy. However its aqueous solubility is very poor. Solid inclusion complexes of fexofenadine and β-cyclodextrin were prepared at the molar ratios of 1:1 and 1:2 by kneading, and coprecipitation methods to improve its solubility. Characterization of the complexes was performed using infrared spectroscopy, X-ray diffractometry, and in vitro dissolution studies. Fexofenadine was found to exhibit interaction with β-cyclodextrin both in solid and liquid state. Phase solubility studies indicated that fexofenadine forms a stable complex with β-cyclodextrin. Both IR spectroscopy and X-ray diffractometry studies indicated interaction of fexofenadine with β-cyclodextrin. Kneading method at 1:1 and co-precipitation method at 1:1 and 1:2 molar ratios showed significant interaction. In vitro dissolution studies confirmed the same results.

ENHANCEMENT OF SOLUBILITY AND DISSOLUTION OF NIMESULIDE USING SOLUBILIZATION, SOLID DISPERSION AND COMPLEXATION TECHNIQUES

Nimesulide is a preferential COX-2 inhibitor. It has high anti-inflammatory, antipyretic and analgesic activities. It has poor aqueous solubility (0.01mg/ml). Solubility of nimesulide was studied using different cosolvent mixtures and various classes of nonionic surfactants. Dimethylacetamide (DMA); at 10% v/v exhibited the highest solubilizing effect (10-fold) towards nimesulide as compared with other cosolvents. Among the tested nonionic surfactants at 10% w/v, brij 58 which exhibited the highest solubilization effect (39-fold). The dissolution of nimesulide from solid dispersions was also studied. Solid inclusion complexes of nimesulide with β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP β-CD) were prepared at a molar ratio of 1:1. Eutectic mixtures were obtained at weight ratio of 1:9 binary systems as confirmed by DSC studies. The dissolution studies indicated that the highest relative amounts dissolved were obtained from solid dispersions as compared with physical mixtures or pure nimesulide. Also higher relative amounts dissolved were obtained with polyvinylpyrrolidones (PVPs) at weight ratio of nimesulide/PVP 40000 1:7. Physicochemical characterization of pure drug, PVP 40000, nimesulide/PVP 40000 solid dispersion and the physical mixture at this ratio were conducted by DSC, FTIR, X-RPD and SEM. The DSC thermograms and X-RPD patterns demonstrated that nimesulide existed in an amorphous form and there is an intermolecular hydrogen bond between the drug and the carrier as shown from FTIR analysis. SEM images confirmed the absence of the crystalline structure of nimesulide in the solid dispersion.

Molecular complexes of aspirin with humic acid extracted from shilajit and their characterization

Aspirin possesses antipyretic, anti-inflammatory, analgesic and anti-aggregatory activity. The acetylsalicylic acid molecule has a carboxyl group and an ester group. The ester group can be easily hydrolyzed, which reduces the medicinal value and causes side effects on humans. The aim of the present study was to prepare solid complexes between aspirin and humic by lyophilization and solvent evaporation technique in the molar ratio 1:1 and 1:2. Molecular interaction between aspirin and humic acid were studied by DSC, XRD, FT-IR and scanning electron microscopy. This technique clearly demonstrated the existence of solid inclusion complex formation. The lyophilized complex in the molar ratio 1:2 showed enhanced stability and dissolution rates of aspirin significantly. A highly significant (p < 0.05) anti-inflammatory action of the treatment of optimized freeze dried (1:2) aspirin complex with humic acid was evidenced by inhibition of rat paw edema and anti-ulcerogenic action was measured by lowest score (0.63 ± 0.10) with significant reduction in ulceration as compared to aspirin alone.

Preparation and physicochemical characterization of carbamazepine (CBMZ): para-sulfonated calix[n]arene inclusion complexes

The formation of inclusion complexes with para-sulfonated calix[n]arene (PSC[n]A) was studied for carbamazepine (CBMZ), a poorly water soluble anticonvulsant drug. The effect of PSC[4]A and PSC[6]A on aqueous solubility of carbamazepine was studied extensively. The complete complexation of the drug was achieved after 48 h of shaking with PSC[n]A in water and evaporation of water to get solid complex. The interaction between PSC[n]A and CBMZ in solid state inclusion complexes was accomplished by aqueous phase solubility studies, HPLC, DSC, PXRD, FTIR, UV–Vis, and FT-Raman spectroscopy. The solubility of CBMZ increases as a function of PSC[n]A concentration. The results of the two phase solubility experiments are in good conformity to signify the formation of 1:1 (PSC[6]A:CBMZ) and 2:1 PSC[4]A:CBMZ complexes. The order of dissolution rate of CBMZ is inclusion complex > physical mixture > drug alone. The purpose of this study was to enhance solubility resulting in high dissolution rate and bioavailability of this essentially water insoluble drug.

Combined hydroxypropyl-β-cyclodextrin and poly(anhydride) nanoparticles improve the oral permeability of paclitaxel

The aim of this work was to study the effect of the combination between 2-hydroxypropyl-β-cyclodextrin (HPCD) and bioadhesive nanoparticles on the encapsulation and intestinal permeability of paclitaxel (PTX). In this context, a solid inclusion complex between PTX and HPCD was prepared by an evaporation method. Then, the complex was incorporated in poly(anhydride) nanoparticles by a solvent displacement method. The resulting nanoparticles, PTX–HPCD NP, displayed a size of about 300 nm and a drug loading of about 170 μg/mg (500-fold higher than in the absence of HPCD). The effect of these nanoparticles on the permeability of intestinal epithelium was investigated using the Ussing chamber technique. The apparent permeability ( P app) of PTX was found to be 12-fold higher when formulated as PTX–HPCD NP than when formulated as Taxol ® (control). Furthermore, when interaction between nanoparticles and the mucosa was avoided, the permeability of PTX significantly decreased. In summary, the association between PTX–HPCD and poly(anhydride) nanoparticles would induce a positive effect over the intestinal permeability of paclitaxel, being the bioadhesion a mandatory condition in this phenomena.