Hydrophilic Polymer Polyvinylpyrrolidone Research Articles

Development and in-vivo assessment of the bioavailability of oridonin solid dispersions by the gas anti-solvent technique

We developed solid dispersions, using the gas anti-solvent technique (GAS), to improve the oral bioavailability of the poorly water-soluble active component oridonin. The solubility of oridonin in supercritical carbon dioxide was measured under various pressures and temperatures. To prepare oridonin solid dispersions using the GAS technique, ethanol was used as the solvent, CO 2 was used as the anti-solvent and the hydrophilic polymer polyvinylpyrrolidone K17 (PVP K17) was used as the drug carrier matrix. Characterization of the obtained preparations was undertaken using scanning electron microscopy (SEM), X-ray diffraction (XRD) analyses and a drug release study. Oridonin solid dispersions were formed and oridonin was present in an amorphous form in these dispersions. Oridonin solid dispersions significantly increased the drug dissolution rate compared with that of oridonin powder, primarily through drug amorphization. Compared with the physical mixture of oridonin and PVP K17, oridonin solid dispersions gave higher values of AUC and C max, and the absorption of oridonin from solid dispersions resulted in 26.4-fold improvement in bioavailability. The present study illustrated the feasibility of applying the GAS technique to prepare oridonin solid dispersions, and of using them for the delivery of oridonin via the oral route.

Self-assembled liposomes from amphiphilic electrospun nanofibers

Amphiphilic nanofibers composed of the hydrophilic polymer polyvinylpyrrolidone K60 (PVP) and soybean lecithin were fabricated using an electrospinning process. As a result of the templating and confinement properties of the nanofibers, phosphatidyl choline (PC) liposomes were spontaneously formed through molecular self-assembly when the fibers were added to water. The sizes of the self-assembled liposomes could be manipulated by varying the content of PC in the nanofibers (over the range 9.1–33.3% (w/w) in the present study). The influence of PC on nanofiber formation, and a possible mechanism of templated liposome formation are discussed. This facile and convenient strategy for manipulating molecular self-assembly to synthesize liposomes provides a versatile new approach for the development of novel drug delivery systems and biomaterials.

Multicomponent Amorphous Nanofibers Electrospun from Hot Aqueous Solutions of a Poorly Soluble Drug

To design and fabricate multicomponent amorphous electrospun nanofibers for synergistically improving the dissolution rate and permeation profiles of poorly water-soluble drugs. Nanofibers were designed to be composed of a poorly water soluble drug, helicid, a hydrophilic polymer polyvinylpyrrolidone as filament-forming matrix, sodium dodecyl sulfate as transmembrane enhancer and mannitol as taste masking agent, and were prepared from hot aqueous co-dissolving solutions of them. An elevated temperature electrospinning process was developed to fabricate the composite nanofibers, which were characterized using FESEM, DSC, XRD, ATR-FTIR, in vitro dissolution and permeation tests. The composite nanofibers were homogeneous with smooth surfaces and uniform structure, and the components were combined together in an amorphous state because of the favorable interactions such as hydrogen bonding, electrostatic interaction and hydrophobic interactions among them. In vitro dissolution and permeation tests demonstrated that the composite nanofibers had a dissolution rate over 26-fold faster than that of crude helicid particles and a 10-fold higher permeation rate across sublingual mucosa. A new type of amorphous material in the form of nanofibers was prepared from hot aqueous solutions of multiple ingredients using an electrospinning process. The amorphous nanofibers were able to improve the dissolution rate and permeation rate of helicid.

Dissolution Improvement of Electrospun Nanofiber-Based Solid Dispersions for Acetaminophen

The objective of the present investigation was to prepare novel solid dispersions (SDs) of poorly water-soluble drugs with special microstructural characteristics using electrospinning process. With the hydrophilic polymer polyvinylpyrrolidone as the filament-forming polymer and acetaminophen (APAP) as the poorly water-soluble drug model, SDs having a continuous web structure, and in the form of non-woven nanofiber membranes, were successfully prepared. The electrospun nanofiber-based SDs were compared with those prepared from three traditional SD processes such as freeze-drying, vacuum drying, and heating drying. The surface morphologies, the drug physical status, and the drug-polymer interactions were investigated by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and attenuated total reflectance Fourier transform infrared. In vitro dissolution tests demonstrated that the electrospun nanofibers released 93.8% of the APAP content in the first 2 minutes and that the dissolution rates of APAP from the different SDs had the following order: electrospun membrane > vacuum-dried membrane approximately freeze-dried membrane > heat-dried membrane. Electrospun nanofiber-based SDs showed markedly better dissolution-improving effects than the other SDs, mainly due to their huge surface area, high porosity resulting from web structure, and the more homogeneous distribution of APAP in the nanofiber matrix.

Preparation of biopolymeric micropatterns via non-residual-layered imprinting technique and its application to modify single-celled microelectrodes

A ‘‘patch clamp’’ microelectrode modified on the surface for single cell adhesion and growth was developed using a novel polymer-transfer technique to deposit cell-adhesive polymer layers on the substrate platform. Several hydrophilic polymers–-polyvinyl pyrrolidone, chitosan, alginic acid, and gelatin were successfully transferred onto the platform in order to enhance cell adhesion. The process was developed to apply a PDMS stamp pre-adhered with a phosphorylcholine (PC) layer on the protruding areas of the pattern, followed by adsorbing an adhesive polymer to imprint the adhesive layer onto the platform. Plasma activation on the stamp, adsorbed polymers, and/or the substrate was evaluated to provide an accessible method to obtain a nanothick (about 180 nm) polymeric film without any residual layer. XPS characterization on the platform verified that the bioactive polymer was only transferred and coated on the convex surfaces of the pattern. From observing the cell adhesion on the chitosan-modified platform, the number of adhered cells on the chitosan layer was found to be greater than that on the original poly(glycidyl methacrylate) (PGMA) layer, corresponding with the prediction that chitosan can serve as the cell-adhesive layer. The modified patterns were found to confine a single cell on each convex top of the platforms.

Physicochemical characterization of sanguinarine-hydroxypropyl-β-cyclodextrin binary and ternary systems

Complexation of sanguinarine with hydroxy-propyl-β-cyclodextrin (HPβCD) in the presence and absence of hydrophilic polymer—polyvinylpyrrolidone K30 was studied. Respective binary and ternary systems were prepared using two techniques, physical mixture and lyophilization, and characterized by FT-infrared spectrometry, differential scanning calorimetry and X-ray diffractometry. The Fourier Transform Infrared spectra of the lyophilized binary and ternary systems showed significant shifts in the regions of 1240–1300 cm−1, 1450–1525 cm−1 and 1600–1650 cm−1, where absorptions of –C–O–C– asymmetrical stretching of sanguinarine rings A and F and νC=C ring vibrations of sanguinarine benzo[c]phenanthridine system can be observed respectively. Moreover, in the case of ternary products νC=O amide band absorption of polyvinylpyrrolidone (1600–1750 cm−1) shifted to the lower wavenumbers in both the physical mixture and the lyophilized product. These changes in the spectra of the studied systems proved the involvement of the respective molecular groups in complexation process. Differential scanning calorimetry and X-ray diffractometry indicated different states of drug amorphization and entrapment in HPβCD in the presence and without polyvinylpyrrolidone. The obtained results let us conclude that obtained binary and ternary systems represent sanguinarine-HPβCD molecular complexes, with different rate of inclusion in the presence and without polyvinylpyrrolidone.

Spectrophotometric Studies of Sanguinarine-Β-Cyclodextrin Complex Formation

The main aim of this study was to investigate the influence of pH and the presence of hydrophilic polymer polyvinylpyrrolidone on the formation of sanguinarine-β-cyclodextrin (SANG-β-CD) inclusion complex. Spectrophotometric studies of the SANG-β-CD systems in the presence and without 0.1 % PVP at the pH 5.0 did not show any evidence of the complex formation. However, the same systems showed several obvious evidences at the pH 8.0: the hyperchromic and the hypochromic effects and the presence of the isosbestic point in the region of 200 – 210 nm. The association constants calculated by three linear methods: Benesi-Hildebrand, Scott and Scatchard, were two times higher for the systems with addition of 0.1% PVP than for the systems without it.

Improved formulation of photosensitizer chlorin e6 polyvinylpyrrolidone for fluorescence diagnostic imaging and photodynamic therapy of human cancer

An improved formulation of the photosensitizer chlorin e6 (Ce6) in combination with the hydrophilic polymer polyvinylpyrrolidone (PVP) was investigated for its potential clinical applications in fluorescence diagnosis and photodynamic therapy (PDT) of cancer. This study reports the comparative preclinical biodistribution and efficacy of Ce6 delivered with or without PVP versus dimethyl sulfoxide (DMSO). The safety and fluorescence pharmacokinetics of Ce6–PVP in humans was also accessed. Biodistribution results showed that Ce6–PVP had higher tumor to normal tissue ratio compared to the other formulations. The sensitivity and specificity derived from the area under the receiver operating characteristics curves showed that the formulations were able to discriminate tumor from peritumoral muscle in the following order: Ce6–PVP > Ce6 > Ce6–DMSO. In vitro PDT results showed that Ce6–PVP was found to induce selective phototoxicity in leukemic cells compared to peripheral mononuclear blood cells. In addition, in vivo light irradiation at 1 h after Ce6–PVP was found to induce greater tumor necrosis without causing animal toxicity. In patients, preferential accumulation of Ce6–PVP was observed in angiosarcoma lesions compared to normal skin following intravenous administration. In conclusion, PVP significantly enhanced the Ce6 concentration in tumors compared with Ce6 alone and increased the therapeutic index of PDT without any side effects in animal model. No serious adverse events were observed in human as well.

Influence of hydrophilic polymers on celecoxib complexation with hydroxypropyl beta-cyclodextrin.

Complexation of celecoxib with hydroxypropyl beta-cyclodextrin (HPbetaCD) in the presence and absence of 3 hydrophilic polymers-polyvinyl pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG)-was investigated with an objective of evaluating the effect of hydrophilic polymers on the complexation and solubilizing efficiencies of HPbetaCD and on the dissolution rate of celecoxib from the HPbetaCD complexes. The phase solubility studies indicated the formation of celecoxib-HPbetaCD inclusion complexes at a 1:1M ratio in solution in both the presence and the absence of hydrophilic polymers. The complexes formed were quite stable. Addition of hydrophilic polymers markedly enhanced the complexation and solubilizing efficiencies of HPbetaCD. Solid inclusion complexes of celecoxib-HPbetaCD were prepared in 1:1 and 1:2 ratios by the kneading method, with and without the addition of hydrophilic polymers. The solubility and dissolution rate of celecoxib were significantly improved by complexation with HPbetaCD. The celecoxib-HPbetaCD (1:2) inclusion complex yielded a 36.57-fold increase in the dissolution rate of celecoxib. The addition of hydrophilic polymers also markedly enhanced the dissolution rate of celecoxib from HPbetaCD complexes: a 72.60-, 61.25-, and 39.15-fold increase was observed with PVP, HPMC, and PEG, respectively. Differential scanning calorimetry and X-ray diffractometry indicated stronger drug amorphization and entrapment in HPbetaCD because of the combined action of HPbetaCD and the hydrophilic polymers.

Modification of the tri-phasic drug release pattern of leuprolide acetate-loaded poly(lactide-co-glycolide) microparticles

Leuprolide acetate-loaded poly(lactide-co-glycolide) (PLGA RG503H) microparticles prepared by the solvent evaporation method had a tri-phasic drug release pattern over a duration of up to 2 months. An initial release was followed by a slow drug release phase and a final rapid drug release. The objective of this study was to identify parameters, which shift the release profile from the tri-phasic to a more continuous release profile. Varying formulation and processing parameters (e.g., drug loading, volume of the external aqueous phase, using low molecular weight PLGA, different microparticle drying methods) affected the initial release (burst) but did not influence the drug release thereafter. The addition of the hydrophilic polymer polyvinylpyrrolidone (PVP) led to the formation of more porous microparticles. This influenced the initial release but did not change the tri-phasic drug release pattern. The inclusion of medium chain triglycerides (MCT) successfully shifted the tri-phasic pattern to a continuous release profile. MCT accelerated the leuprolide release in the second, slow release phase and reduced it in the final rapid release phase. MCT led to the formation of microparticles with an irregular surface and a highly porous inner structure. Differential scanning calorimetry (DSC) revealed a high encapsulation efficiency of MCT (88–105%) in the microparticles and an unchanged glass transition temperature ( T g) of PLGA.