Biomedical subjects

Weisan Pan

Publications and source records attributed to Weisan Pan.

12 recordsLinked to original sources

PubMed2006

Investigation into the potential of low-frequency ultrasound facilitated topical delivery of Cyclosporin A.

The potential for low-frequency ultrasound facilitated topical transport of Cyclosporin A was investigated using rat skin. Studies of intensity and exposure time acting on the deposition of Cyclosporin A into deeper skin of in vitro sonophoresis were performed. Low-frequency ultrasound increased the amount of Cyclosporin A retained in the skin only seven times than the passive diffusion. Furthermore, we also tested the synergistic effect of ultrasound and other approaches such as chemical enhancers and electroporation on topical drug delivery of Cyclosporin A. We found that the efficacy of low-frequency ultrasound in enhancing topical delivery could be further increased by pretreatment of skin with chemical enhancers, such as laurocapram (Azone) and sodium lauryl sulfate (SLS). Meanwhile only a small amount was seen to across the full skin into the receiver compartment. Trimodality treatment comprising of pretreatment with Azone+ultrasound in combination followed by electroporation was not effective in enhancing the topical delivery of Cyclosporin A. However, this combination strategy increased the penetration of Cyclosporin A through rat skin by order of 15. The histopathological findings revealed that there was almost no change observed in the structure of skin after ultrasound or combination with ultrasound and enhancers as compared with the control group. In general, the enhanced skin accumulation of Cyclosporin A by the combination of low-frequency ultrasound and chemical enhancers could help significantly to optimize the targeting of the drug without of a concomitant increase of the systemic side effects.

Administration, Cutaneous↗

PubMed2006

Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin.

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal elimination of the drug may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and then undergo a sol-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, gatifloxacin, based on the concept of ion-activated in situ gelation. Alginate (Kelton) was used as the gelling agent in combination with HPMC (Methocel E50Lv) which acted as a viscosity-enhancing agent. The rheological behaviors of all formulations were not affected by the incorporation of gatifloxacin. Both in vitro release studies and in vivo pre-corneal retention studies indicated that the alginate/HPMC solution retained the drug better than the alginate or HPMC E50Lv solutions alone. These results demonstrate that the alginate/HPMC mixture can be used as an in situ gelling vehicle to enhance ocular bioavailability and patient compliance.

Alginates↗

PubMed2006

Delivery of different length poly(L-lysine)-conjugated ODN to HepG2 cells using N-stearyllactobionamide-modified liposomes and their enhanced cellular biological effects.

Short (14-20-mer range) synthetic oligodeoxynucleotides (ODNs) allow specific modulation of cellular gene expression at various stages, thus providing a versatile tool for fundamental studies and a rational approach to anticancer chemotherapy. However, several problems, such as metabolic stability, efficient cell internalization of ODNs and their efficient entrapment into liposomes continue to markedly limit this approach. To improve the target specificity and biological activity of ODN, three different length of poly(L-lysine) (PLL) were conjugated to ODN and these conjugates were encapsulated in N-stearyllactobionamide (N-SLBA)-modified liposomes, N-SLBA is a ligand for the asialoglycoprotein receptor. Then, we investigated their effects on cell cycle and survivin protein levels of HepG2 cells. The results showed that the encapsulation efficiency was improved because the polycationic charges of PLL neutralized the polyanionic charges of ODN. Among them, PLL (M(W) 2000 and 10,000)-conjugated ODN encapsulated in N-SLBA liposomes induced apoptosis of HepG2 cells and highly inhibited survivin gene expression.

Apoptosis↗

PubMed2006

Effects of Transcutol P on the corneal permeability of drugs and evaluation of its ocular irritation of rabbit eyes.

Our purpose was to explore the use of Transcutol P (Trans) in an ocular drug delivery system. The effect of Trans on the corneal permeability of drugs was investigated in-vitro, using isolated rabbit corneas. The ocular irritation of Trans was also tested in rabbits in-vivo. In the presence of Trans, at a concentration of 0.005-0.03%, the maximum increase in the apparent permeability coefficient (P(app)) was 1.5, 1.5, 3.0 and 3.3 fold for ribavirin, gatifloxacin, levofloxacin hydrochloride and enoxacin, respectively. However, the P(app) value of oxaprozin was reduced in the presence of Trans. The maximum reduction was found to be 2.8 fold at a concentration of 0.03% Trans. The results of the ocular irritation studies showed that Trans was non-irritant at the concentrations studied (0.005-0.03%), while it produced slight irritation at a concentration of 0.05%. It was also found that Trans did not cause any visible ocular damage or abnormal clinical signs involving the cornea, iris or conjunctivae at all concentrations. We concluded that Trans may have potential clinical benefits in improving the ocular drug delivery of hydrophilic compounds.

1-Octanol↗

PubMed2006

Effects of isopropyl palmitate on the skin permeation of drugs.

The model penetrants oxaprozin, nimesulide, gliclazide, and ribavirin, because of their different lipophilicities, were selected to assess the enhancing activity of pre-treatment solutions consisting of isopropyl palmitate (IP) in ethanol (5%, 10%, 15%and 20%, w/w, respectively) across excised rat skin using Franz diffusion cells and HPLC detection. All pre-treatment solutions produced a significant increase in the flux and permeation of all four penetrants (p<0.001) and a relationship between penetrant lipophilicity and enhancement effect was observed. The general order of IP effectiveness at concentration was 20%>15%>10%>5% (w/w). The lag-time of drugs did not significantly change except for ribavirin.

Abdomen↗

PubMed2006

The permeation of nalmefene hydrochloride across different regions of ovine nasal mucosa.

The permeability of nalmefene hydrochloride (NH) across different regions of ovine nasal mucosa was investigated in vitro. Five different regions of ovine nasal mucosa (superior turbinate mucosa, middle turbinate mucosa, inferior turbinate mucosa, posterior septum mucosa, and anterior septum mucosa) were studied. The results showed that the permeability coefficients of NH through different regions of nasal mucosa were different, and the suitable regions for the absorption of NH were the middle turbinate mucosa, the posterior septum mucosa and the superior turbinate. At the same time, the middle turbinate mucosa was the largest region among the five regions, thus it was the main absorption region for NH. The high uniformity of the middle turbinate mucosa also made it the most suitable model for the permeation of NH in vitro.

Animals↗

PubMed2005

Preparation and evaluation of SEDDS and SMEDDS containing carvedilol.

A new self-emulsifying drug delivery system (SEDDS) and self-microemulsifying drug delivery system (SMEDDS) have been developed to increase the solubility, dissolution rate, and, ultimately, oral bioavailability of a poorly water soluble drug, carvedilol. Ternary phase diagrams were used to evaluate the self-emulsification and self-microemulsfication domains. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The minimum self-emulsification time was found at a Tween 80 content of 40%. The particle size distribution and zeta-potential were determined. Benzoic acid had a dual function, it improved the self-emulsification performance of SEDDS and SMEDDS in 0.1 N HCl and lead to a positively charged emulsion. The in vitro dissolution rate of carvedilol from SEDDS and SMEDDS was more than two-fold faster compared with that from tablets. The developed SEDDS formulations significantly improved the oral bioavailability of carvedilol significantly, and the relative oral bioavailability of SEDDS compared with commercially available tablets was 413%.

Adrenergic alpha-Antagonists↗

PubMed2005

Preparation and evaluation of sustained ophthalmic gel of enoxacin.

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid precorneal elimination of the drug may be overcome by the use of a gel system. The present work describes the formulation and evaluation of an ophthalmic delivery system containing an antibacterial agent, enoxacin, based on the concept of ophthalmic sustained gel, in which 2-hydroxypropyl-beta-cyclo-dextrin (HP-beta-CD) was used as a penetration enhancer in combination with hydroxypropylmethylcellulose (Methocel F4M) which acted as a vehicle. The developed formulation was therapeutically efficacious, nonirritant, and provided sustained release of the drug over 8 h period in vitro and 7 h period in vivo. The developed system is a viable alternative to conventional eye drops.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2005

Design and evaluation of compound metformin/glipizide elementary osmotic pump tablets.

A simple elementary osmotic pump (EOP) system that could deliver metformin hydrochloride (MT) and glipizide (GZ) simultaneously for extended periods of time was developed in order to reduce the problems associated with multidrug therapy of type 2 non-insulin-dependent diabetes mellitus. In general, both highly and poorly water-soluble drugs are not good candidates for elementary osmotic delivery. However, MT is a highly soluble drug with a high dose (500 mg) while GZ is a water-insoluble drug with a low dose (5 mg) so it is a great challenge to pharmacists to provide satisfactory extended release of MT and GZ. In this paper sodium carbonate was used to modulate the solubility of GZ within the core and MT was not only one of the active ingredients but also the osmotic agent. The optimal EOP was found to deliver both drugs at a rate of approximately zero order for up to 10 h in pH 6.8, independent of environment media. In-vivo evaluation was performed relative to the equivalent dose of conventional MT tablet and GZ tablet by a cross-study in six Beagle dogs. The EOP had a good sustained effect in comparison with the conventional product. The prototype design of the system could be applied to other combinations of drugs used for cardiovascular diseases, diabetes, etc.

Delayed-Action Preparations↗

PubMed2005

Preparation and characterization of a novel pH-sensitive ion exchange resin.

Methylacrylic acid/styrene cross-linked with divinylbenzene is a novel pH-sensitive ion exchange resin. Microspheres of this resin were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The microspheres showed a pulsatile swelling behavior when the pH of the media changed. The pH-sensitive microspheres were loaded with salbutamol sulfate and the drug-release characteristics were studied under both simulated gastric and intestinal pH conditions. The results obtained showed that the drug release also depended on the pH of the release media.

Hydrogen-Ion Concentration↗

PubMed2004

The effect of citric acid added to hydroxypropyl methylcellulose (HPMC) matrix tablets on the release profile of vinpocetine.

Vinpocetine is a pH-dependent experimental drug with a short half-life. The sustained-release matrix tablets of vinpocetine were prepared by direct compression using hydroxypropyl methylcellulose (HPMC) and different amounts of citric acid to set up a system bringing about gradual release of this drug. In order to investigate the influence of citric acid and the pH value of medium on the drug release from HPMC matrix tablets, an in vitro release test was carried out in either phosphate buffer pH 6.8 [0.5% sodium dodecyl sulfate (SDS)] for 12 hr or in 0.1 N HCl (0.5% SDS) (0-2 hr) and phosphate buffer pH 6.8 (0.5% SDS) (2-12 hr). Dissolution curves were described by the Peppas equation: M(t)/M(inf)=ktn, and the influence of citric acid on the dissolution mechanism was estimated according to the regression parameter-n and k values. The addition of citric acid and the pH value of medium could notably influence the dissolution behavior and mechanism of drug-release from matrices. Increasing the amounts of citric acid produced an increase in drug release rate, which showed a good linear relationship between contents of citric acid and drug accumulate release (%) in phosphate buffer pH 6.8 (0.5% SDS) (r>0.99). Moreover, a higher drug release rate could be found in 0.1 N HCl (0.5% SDS) than that in phosphate buffer pH 6.8 (0.5% SDS) during the first two hours when the content of citric acid added to matrices was lower than 45 mg/tab., but no significant difference could be found when the content of citric acid was above that value. Increasing amounts of citric acid produced decreasing values of n and increasing values of k, in a linear relationship, which indicated there was a trend favoring the mechanism of diffusion with the addition of increasing quantities of citric acid.

Buffers↗

PubMed2002

Cyclodextrin complex osmotic tablet for glipizide delivery.

Poorly soluble glipizide was selected as the model drug to prepare osmotic pump tablets (OPT) with proper accessorial material after it was made an inclusion complex by kneading method in order to increase solubility. Polyethylene glycol 4000 (PEG4000) and cellulose acetate (CA) were selected as the coating materials, and acetone-water (95:5) co-solvent was employed as the coating medium. The effects of the osmotic promoting agent, diameter of the drug-releasing orifice, coating composition, and coat weight on the drug release profile were investigated. The drug release profile of the optimal formulation was compared with a commercialized push-pull osmotic tablet. The results indicated that glipizide-cyclodextrin inclusion complex OPT had excellent zero-order release characteristics in vitro.

Calorimetry, Differential Scanning↗