The polymer free volume as a controlling factor for drug release from poly(lactide‐co‐glycolide) microspheres

Drug release from poly(lactide‐co‐glycolide) (PLGA) microspheres is strongly determined by the pore structure of the particles. This study examines how swelling‐induced pore constriction delays the drug release and by which factors this process is controlled. Combination of different porosimetric and pycnometric methods enabled insight into the submicroscopic range of the pore structure and revealed that remarkably the polymer free volume plays a crucial role in drug release from PLGA microspheres. Surprisingly, the latter was shown to be inversely correlated to the degree of diffusional drug release. This can be explained by a swelling‐induced constriction of the macroporous channel system in the microspheres which is related to the availability of free volume. The hole free volume was shown to be well controllable by the manufacturing conditions. Thus, the study deepens comprehension of the mechanism of drug release from biodegradable microparticles and offers an effective approach for controlling the release behavior. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39740.     

Gelatin‐carbohydrate phase‐separated hydrogels as bioactive carriers in vaginal delivery: Preparation and physical characterizations

The current study focuses on the alteration of properties of the gelatin hydrogels using polysaccharides (e.g., maltodextrin, dextran, and sodium carboxymethyl cellulose) for probable use in vaginal delivery of antimicrobials. The hydrogels were prepared by varying the proportions of gelatin and polysaccharides and were characterized by microscopy, mechanical testing, and impedance spectroscopy. Metronidazole (MZ), drug of choice for the treatment of bacterial vaginosis, was incorporated within the hydrogels. In vitro release studies of MZ from the hydrogels was studied in‐depth using modified Franz's diffusion cell. Antimicrobial efficiency of the MZ‐loaded hydrogels was tested against E. coli and B. subtilis. The results suggested that the incorporation of polysaccharides resulted in the phase‐separated hydrogels. The properties of the hydrogels was found be suitable for vaginal delivery. The drug release and antimicrobial efficiency from the hydrogels suggested that the developed hydrogels may be used for the delivery of antimicrobials in the vaginal lumen. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40445.     

Drug‐loaded polyurethane/clay nanocomposite nanofibers for topical drug‐delivery application

In this study, polyurethane/nanoclay nanocomposite nanofibrous webs were prepared by electrospinning. An antiseptic drug, chlorhexidine acetate (CA), was loaded onto montmorillonite clay and was then incorporated into polyurethane nanofibers. For comparison, the CA drug was loaded directly into the polyurethane solution dope used to electrospin the nanofibers. The emphasis was on investigating the effect of the drug loading into the nanoclay vis‐à‐vis direct drug loading on the drug‐release behavior of nanofibrous webs. The nanofibrous webs were also evaluated for other properties, such as moisture vapor transmission, porosity determination, contact angle measurement, and antibacterial activity, which are important for topical drug‐delivery application. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40230.     

Encapsulation of animal wax‐based organogels in alginate microparticles

Encapsulation of organogels is a novel perspective in the field of controlled drug delivery. This study reports encapsulation of lanolin based organogels within alginate microparticles. The microparticles were prepared by emulsification/internal gelation method. Microscopic studies suggested spherical shape of the microparticles. Fourier transform infrared, X‐ray diffraction and thermal studies confirmed the presence of organogels within the microparticles. Organogels containing microparticles showed improved drug (e.g., salicylic acid and metronidazole) entrapment efficiency. The release of the drugs from the microparticles was dependent on the pH of the dissolution medium. The release was diffusion mediated. The drug loaded microparticles showed antimicrobial activity against E. coli and B. subtilis. The preliminary study suggested that the encapsulation of the organogels may help prolonging the release of the drugs and hence may be tried as vehicles for controlled drug delivery. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40910.     

Temperature/pH dual responsive microgels of crosslinked poly(N‐vinylcaprolactam‐co‐undecenoic acid) as biocompatible materials for controlled release of doxorubicin

Undecenoic acid functionalized thermo/pH responsive microgels, poly(N‐vinylcaprolactam‐co‐undecenoic acid) [poly(VCL‐co‐UA)], were synthesized by precipitation emulsion copolymerization. The microgels exhibit reversible thermo/pH responsive phase transition behavior, which can be tuned by varying the monomer feed ratio. The lower critical solution temperatures (LCSTs) of the materials are close to body temperature. As a result, when temperatures rise above ca. 37°C, a rapid thermal gelation process occurs, accompanied by a phase transition, resulting in expulsion of encapsulated compound. In vitro experiment evaluated its applicability as a drug carrier for controlled release of an anticancer agent (doxorubicin) and showed that the drug encapsulation efficiency (EE), releasing rate, and kinetics are dependent on the temperature and pH value as expected. Minimal cytotoxicity of the microgels was observed by a cytotoxicity assay using 3T3 fibroblast cells. Our finding suggests that the poly(VCL‐co‐UA) based microgels may be considered a promising candidate for temperature or pH‐controlled delivery of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41146.     

In vitro evaluation of spray‐dried chitosan microspheres crosslinked with pyromellitic dianhydride for oral colon‐specific delivery of protein drugs

Chitosan microspheres have been prepared using a spray‐drying method, and crosslinked with pyromellitic dianhydride. The chemical structure of the modified chitosan was characterized by FTIR spectroscopy and solid state 13C NMR analysis. The particle size and morphology of the crosslinked chitosan were investigated. These microspheres were evaluated for colon‐specific delivery of bovine serum albumin (BSA) as a model protein drug. The results indicate that the drug was released as follows: 37.1 ± 2.8% after 2 h in SGF, 73.1 ± 4.8% after 8 h (2 h in SGF+ 6 h in SIF), and 80.9 ± 4.1% after 12 h in SCF. The effect of β‐glucosidase on the drug release was also examined. The encapsulation efficiency was decreased from 88.4 ± 3.1% to 62.8 ± 2.9%, with increasing BSA concentration. Loading capacity was significantly increased from 6.3 ± 0.3% to 41.8 ± 4.1% by increasing the initial BSA concentration. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40514.     

Complex of cisplatin with biocompatible poly(ethylene glycol) with pendant carboxyl groups for the effective treatment of liver cancer

Cisplatin was incorporated into polymeric carriers through the coordination of Pt with the carboxylic groups of methoxy‐poly(ethylene glycol) (mPEG)‐block‐poly[(2‐carboxy‐ethylsulfanyl)‐propyl glycidyl ether] (PCPGE). The mPEG‐b‐PCPGE/Pt complexes with a Pt content of 14 wt % could self‐assemble into spheric micelles with diameter of about 80 nm in aqueous solution. The effective internalization of the polymer platinum micelles by the cells via an endocytosis mechanism was confirmed by confocal laser scanning microscopy and flow cytometry. The antitumor activity of the polymeric micelles was similar to that of cisplatin in vitro. The in vivo blood clearance of platinum was studied, and the results show that the micelles exhibited longer blood circulation than the free cisplatin. The biodistribution of cisplatin and its micelles in mice was studied through the measurement of the Pt content in plasma, organs, and tumors, especially in tumor cell DNA. Their antitumor activity in vivo, assessed in mice bearing H22 liver cancers, showed that the micelles exhibited greater antitumor efficacy than free cisplatin. Therefore, this polymer platinum micelle is a promising candidate as a smart antitumor drug carrier for malignancy therapy in future clinical applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40764.     

Efficient loading and entrapment of tamoxifen in human serum albumin based nanoparticulate delivery system by a modified desolvation technique

Herein, the poorly water-soluble drug, Tamoxifen (Tmx), was loaded in the amphipathic matrix of human serum albumin (HSA) nanoparticles by a modified desolvation method. In order to enhance the drug loading (DL) and drug entrapment efficiency (DEE) (<2% and 10%, respectively), ultrasonication of Tmx-HSA mixture was performed prior to desolvation process. Tmx loading and entrapment efficiency were optimized by employment of the response surface methodology (RSM)-central composite design (CCD) of experiments. Under the optimum conditions of 1.59 mg Tmx/ml concentration, 7.76 pH and 5 h incubation of HSA-Tmx, the DL of 6.7% and DEE of 74% are achievable. Particles with the average size of 195 nm, zeta potential of −21 mV and polydispersity index of 0.09 were produced under these conditions. A more sustained Tmx release behavior was observed from polyethylene glycol (PEG) conjugated nanoparticles in comparison to the non-PEGylated ones. The short-term stability investigation showed no alteration in physicochemical properties of nanoparticles at 4 and 37 °C, but small increase in nanoparticles size was observed after three months of storage at room temperature. This is the first report for efficient production of a Tmx delivery system based on HSA nanoparticles.     

刺激响应性聚合物纳米胶束在药物控释中的应用研究

聚合物纳米胶束不仅可以提高药物的溶解度、生物利用度,延长药物在人体内的循环时间,还可以有效控制药物的释放而实现靶向治疗效果,极大地减少药物对人体的副作用。通过嵌段共聚物的纳米工程,可制备出具有细胞或组织靶向性且对物理或化学刺激敏感的高分子药物载体。本文综述了对pH值、温度、超声波和光具有响应性的聚合物纳米胶束的制备及其在药物控制释放领域的应用。     

微/纳米药物给药系统的研究进展

在过去的几十年中,探索高效的微/纳米给药系统一直是药剂学领域的研究热点。不同的微/纳米颗粒已被用于药物输送的研究,以期实现有效靶向给药,最大限度地减少副作用,从而提高治疗效果。本文主要综述了微/纳米药物输送给药系统及在药物制剂领域应用。