• Archives of Pharmacal Research
• /
• v.28 no.3
• /
• pp.364-369
• /
• 2005

HPMC (Hydroxypropyl methylcellulose) was chemically modified, using maleic anhydrides, to obtain pH-sensitive HPMCAM (Hydroxypropyl methylcellulose acetate maleate) polymers for use as novel duodenum-specific coating agents. The pharmaceutical properties of HPMCAM, such as film forming, acid values, pH-sensitive values, water vapor permeability, tensile strength and Tg, were investigated, and found to show good film forming properties. The pH­sensitive values were 3.0 to 3.7. In vitro results demonstrate that HPMCAM could completely suppress drug release within 2h in a simulated gastric fluid (pH 1.2) and rapidly release the drug in a simulated pathological duodenal fluid (pH 3.4). These results indicate that HPMCAM might be a useful material for a duodenum-specific drug delivery system.

• Archives of Pharmacal Research
• /
• v.29 no.12
• /
• pp.1164-1170
• /
• 2006

A triptolide-lysozyme (TP-LZM) conjugate was synthesized to achieve renal specific delivery and to reduce the side effects of triptolide. Triptolide was coupled to lysozyme through succinic via an ester bond with an average coupling degree of 1 mol triptolide per 1 mol lysozyme. The lysozyme can specifically accumulate in the proximal tubular cells of the kidney, making it a potential carrier for targeting drugs to the kidney. The structure of triptolide succinate (TPS) was confirmed by IR, $^{1}H-NMR$, MS and UV. The concentrations of triptolide in various samples were determined by reversed-phase high-performance liquid chromatography (HPLC). In this study, the physicochemical and stability profiles of TP-LZM under various conditions were investgated the stability and releasing profiles of triptolide-lysozyme (TP-LZM) under various conditions. In vitro release trails showed triptolide-lysozyme was relatively stable in plasma (less than 30% of free triptolide released) and could release triptolide quickly in lysosome (more than 80% of free triptolide released) at $37^{\circ}C$ for 24 h. In addition, the biological activities of the conjugate on normal rat kidney proximal tubular cells (NRK52E) were also tested. The conjugate can effectively reduce NO production in the medium of NRK52E induced by lipopolysaccharide (LPS) but with much lower toxicity. These studies suggest the possibility to promote curative effect and reduce its extra-renal toxicity of triptolide by TP-LZM conjugate.

• Korean Chemical Engineering Research
• /
• v.61 no.4
• /
• pp.570-575
• /
• 2023

Targeted anticancer drug delivery systems are needed to enhance therapeutic efficacy by selectively delivering drugs to tumor cells while minimizing off-target effects, improving treatment outcomes and reducing toxicity. In this study, a silica-based nanocarrier capable of targeting drug delivery to cancer cells was developed. First, silica nanoparticles were synthesized by the Stöber method using the surfactant cetyltrimethylammonium bromide (CTAB). Increasing the ratio of EtOH in the solvent produced uniformly spherical silica nanoparticles. Washing the nanoparticles removed unreacted residues, resulting in a non-toxic carrier for drug delivery in cells. Upon surface modification, the pH-responsive polymer, polyethyleneimine (PEI) exhibited slow doxorubicin release at pH 7.4 and accelerated release at pH 5.5. By exploiting this feature, we developed a system capable of targeted drug release in the acidic tumor microenvironment.

• Journal of Biomedical Engineering Research
• /
• v.43 no.2
• /
• pp.94-101
• /
• 2022

Recent advancement of micro/nano technology enables the development of diverse micro/nano particle-based delivery systems. Due to the multi-functionality and engineerability, particle-based delivery system are expected to be a promising method for delivery to the target cell. Since the particle-based delivery system should be delivered to the various kinds of target cell, including the cardiovascular system, cancer cell etc., it is frequently decorated with multiple kinds of targeting molecule(s) to induce specific interaction to the target cell. The surface decorated molecules interact with the cell surface expressed molecule(s) to specifically form a firm adhesion. Thus, in this study, the probability of adhesion is estimated to predict the possibility to form a firm adhesion for the multi-ligand decorated particle-based delivery system.

• Macromolecular Research
• /
• v.15 no.6
• /
• pp.547-552
• /
• 2007

Water soluble polymer, poly(vinyl pyrrolidone) was chosen to conjugate with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) (N-succinyl DPPE) to make a new drug delivery system. PVP with an amine group (amino-PVP) was polymerized by free radical polymerization. The amine group of amino-PVP was conjugated with the carboxylic group of N-succinyl DPPE. The resultant conjugate could form nanoparticles in the aqueous solution; these nanoparticles were termed a lipid-polymer system. The critical aggregation concentration was measured with pyrene to give a value of $1{\times}10^{-3}g/L$. The particle size of the lipid-polymer system, as measured by DLS, AFM and TEM, was about 70 nm. Lipophilic component in the inner part of the lipid-polymer system could derive the physical interaction with hydrophobic drugs. Griseofulvin was used as a model drug in this study. The loading efficiency and release profile of the drug were measured by HPLC. The loading efficiency was about 54%. The release behavior was sustained for a prolonged time of 12 days. The proposed lipid-polymer system with biodegradable and biocompatible properties has promising potential as a passive-targeting drug delivery carrier because of its small particle size.

• Archives of Pharmacal Research
• /
• v.26 no.12
• /
• pp.1096-1101
• /
• 2003

To enhance the liver targeting and reduce the side effects of 5-fluorouracil (5-Fu), it was acylated by stearyl chloride to obtain .$\b{N}_{\b{1}}$stearyl-5-Fu (5-FuS). The chemical structure of the prodrug was confirmed by Nuclear Magnetic Resonance and Infrared Spectrometry. 5-FuS was incorporated into solid lipid nanoparticles (SLN), which were prepared by the physical agglomeration method. The mean diameter of 5-FuS-SLN was 240.19 nm and the drug loading was 20.53%. The release characteristics in vitro of 5-FuS-SLN were fitted to the first-order pharmacokinetic model. Compared with 5-Fu injection, a study on the distribution of 5-FuS-SLN in mice showed that 5-FuS-SLN could double 5-Fu concentration in mice livers. The main pharmacokinetic parameters of 5-FuS-SLN in rabbits is shown as follows: $V_d$=0.04336L/kg, $T_{1/2} \beta$=1.2834h, CL=0.1632 L/h. In conclusion, 5-FuS-SLN has significant liver targeting properties. The employment of a prodrug to enhance drug liposoluble properties and the preparation method presented in this paper, seem to be an alternative strategy to the traditional colloidal delivery system.

• Archives of Pharmacal Research
• /
• v.8 no.3
• /
• pp.159-168
• /
• 1985

In attempt to develop a drug delivery system using serum albumin microspheres, bovine serum albumin microspheres containing antitumor agent, cytarabine, were prepared. The shape, surface characteristics, size distribution, behavior of in vitro distribution, drug release behaior, and degradation of albumin microspheres in animal liver tissue homogenate and proteolytic enzyme were investigated. The shape of albumin microspheres was spherical and the surface was smooth and compact. The size distribution of the albumin microspheres was affected by dispersion forces during emulsification and albumin concentration. Distribution of albumin mirospheres after intravenous administration in rabbit was achieved immediately. In vitro, albumin microsphere matrix was so hard that it retained most of cytarabine except initial burst during the first 10 minutes, and the level of drug release during the initial burst was affected by heating temperature, drug/albumin concentration ratio and size distribution. After drug release test, the morphology of albumin micropheres was not changed. Albumin microsphere matrix was degraded by the rabbit liver tissue homogenate and proteolytic enzyme. The degree of degradation was affected by heating temperature.

• Biomaterials Research
• /
• v.22 no.4
• /
• pp.290-302
• /
• 2018

Background: The main purpose of drug delivery systems is to deliver the drugs at the appropriate concentration to the precise target site. Recently, the application of a thin film in the field of drug delivery has gained increasing interest because of its ability to safely load drugs and to release the drug in a controlled manner, which improves drug efficacy. Drug loading by the thin film can be done in various ways, depending on type of the drug, the area of exposure, and the purpose of drug delivery. Main text: This review summarizes the various methods used for preparing thin films with drugs via Layer-by-layer (LbL) assembly. Furthermore, additional functionalities of thin films using surface modification in drug delivery are briefly discussed. There are three types of methods for preparing a drug-carrying multilayered film using LbL assembly. First methods include approaches for direct loading of the drug into the pre-fabricated multilayer film. Second methods are preparing thin films using drugs as building blocks. Thirdly, the drugs are incorporated in the cargo so that the cargo itself can be used as the materials of the film. Conclusion: The appropriate designs of the drug-loaded film were produced in consideration of the release amounts and site of the desired drug. Furthermore, additional surface modification using the LbL technique enabled the preparation of effective drug delivery carriers with improved targeting effect. Therefore, the multilayer thin films fabricated by the LbL technique are a promising candidate for an ideal drug delivery system and the development possibilities of this technology are infinite.

• Archives of Pharmacal Research
• /
• v.10 no.1
• /
• pp.42-49
• /
• 1987

This study is to evaluate the potential use of aclarubicin-loaded gelatin microspheres as an intravascular biodegradable drug delivery system for the regional cancer therapy. The diameter of the microspheres prepared by water in oil emulsion polymerization could be controlled by adjusting the stirring rate in the range of 10-50 $\mu$m : D(in $\mu$m) = -73.8 log (rpm) + 262.7. The addition of proteolytic enzyme increased the in vitro aclarubicin release but it did not change the amount of the initial burst release which reached about 45%. Microspheres injected intravenously into the mouse tail vein embolized only to the lung when observed by fluorescence microscopy. From histological examination following injection of gelatin microspheres into mouse femoral muscle, mild inflammation was observed from the appearance of neutrophils after 2 days and rapid repair process was confirmed thereafter. Biodegradation process of gelatin microspheres lodged on the pulmonary capillary bed was followed up by microscopic observation; degradation was taking place by about 36 hrs, followed by severe damage on the spheerical shape and microspheres was no longer found 10 days after injection.

• Journal of Pharmaceutical Investigation
• /
• v.19 no.4
• /
• pp.195-202
• /
• 1989

In attempt to improve the chemotherapeutic activity of adriamycin, adriamycin-entrapped HSA microspheres were prepared and investigated by the various in vitro experiments. The shape, surface characteristics and size distribution of HSA microspheres are observed by scanning electron microscopy. The in vitro drug release, albumin matrix degradation by protease of HSA microspheres were studied. The shape of HSA microspheres were spherical and the surface was smooth and compact. The size of HSA microspheres ranged from 0.4 to $2.5\;{\mu}m$ and have average diameters of 0.5 to $0.7\;{\mu}m$. The size distribution of HSA microspheres prepared by ultrasonication was mainly affected by albumin concentration and heating time in the process of hardening. In in vitro, almost all adriamycin was released from HSA microspheres for 8 hr. Analysis of the resulting adriamycin release profiles demonstrated that adriamycin is released from the microspheres in two distinct steps, a fast phase (until 30 min) followed by a much slower sustained release phase. Drug release, which is due to diffusion, was depended on the rate of matrix hydration. Drug release was largely affected by albumin concentration and heating temperature during the process of hardening. Albumin matrix degradation of HSA microspheres was affected by heating temperature and albumin concentration. Higher temperature and longer times generally produce harder, less porous, and slowly degradable microspheres.