Production of polycaprolactone–polyethylene glycol–sodium alginate biocomposites for spray drying encapsulation of <Emphasis Type="SmallCaps">l</Emphasis>-ascorbic acid

l-Ascorbic acid was encapsulated in biopolymers to enhance (1) its encapsulation efficiency and (2) drug release ratio using different pH media. To achieve this goal, we used polycaprolactone (PCL), polyethylene glycol (PEG), and sodium alginate (SA) to prepare drug delivery system and spray dryer as our tool to obtain microspheres. In this manner, the importance of the study was to produce a stable and effective drug encapsulation system by PCL–PEG–SA polymer mixture by spray dryer. First we evaluated the effects of drying conditions and composition on the microencapsulation formulation and in the next stage the most uniformly distributed particles were selected and l-ascorbic acid was loaded. After that, drug encapsulation and drug release studies were performed. Drug release experiments were conducted at different pH solutions (pH 2.5, 7.4, and 9.6). Finally, drug release kinetics was determined by widely used equations to describe the degradation kinetics; zero-order, first-order, Higuchi, Hixson–Crowell, and Korsmeyer–Peppas. Furthermore, l-ascorbic acid release mechanism from microspheres was also determined. The release profiles of three microspheres obeyed the earlier developed kinetic models for performing possible release mechanisms. The Korsmeyer–Peppas model best described each release scenario.     

羧甲基纤维素-大豆分离蛋白农药缓释颗粒的制备及性能

为提高农药利用率、精确控制农药释放,设计了一种pH响应型缓释颗粒。以3-氨丙基三乙氧基硅烷（APTES）为桥连接羧甲基纤维素（CMC）与大豆分离蛋白（SP）得到羧甲基纤维素-大豆分离蛋白（CMC-SP）,然后利用分子自组装法负载阿维菌素（AVM）形成载药颗粒（CMC-SP@AVM）。采用红外光谱（FTIR）、扫描电镜（SEM）、热重分析（TGA）等手段对改性产物结构和形貌进行表征,并对CMC-SP@AVM的载药性能、缓释性能、抗紫外性能、杀虫活性进行了探究。结果表明,CMC-SP@AVM具有近似椭圆形的结构,CMC-SP@AVM的平均粒径为104nm;对AVM的包封率达41.9%,并赋予AVM优异的抗紫外光分解性能,强紫外光照射120h后,CMC-SP@AVM中AVM的残留率比未包封的AVM高117%,其药物释放具有pH响应特性,pH越大,释放速率越快;药物释放过程符合Elovich模型。在相同AVM浓度下CMC-SP@AVM的杀虫活性与原药无显著差异。     

Enhanced gastric retention and drug release via development of novel floating microspheres based on Eudragit E100 and polycaprolactone: synthesis and in vitro evaluation

Eudragit E 100 and polycaprolactone (PCL) floating microspheres for enhanced gastric retention and drug release were successfully prepared by oil in water solvent evaporation method. Metronidazole benzoate, an anti-protozoal drug, was used as a model drug. Polyvinyl alcohol was used as an emulsifier. The prepared microspheres were observed for % recovery, % degree of hydration, % water uptake, % drug loading, % buoyancy and % drug release. The physico-chemical properties of the microspheres were studied by calculating encapsulation efficiency of microspheres and drug release kinetics. Drug release characteristics of microspheres were studied in simulated gastric fluid and simulated intestinal fluid i.e., at pH 1.2 and 7.4 respectively. Fourier transform infrared spectroscopy was used to reveal the chemical interaction between drug and polymers. Scanning electron microscopy was conducted to study the morphology of the synthesized microspheres.     

Spray drying technique to produce controlled release formulations of zidovudine—an anti‐HIV drug

This article explores the application of spray drying technique to produce microparticles of poly(D ,L ‐lactide‐co‐glycolic acid) (PLGA), as well as di‐block copolymer of polylactic acid (PLA) and polyethylene glycol (PEG) (PLA‐PEG), containing zidovudine (AZT), an anti‐HIV drug, to achieve its controlled release over an extended period of time. Of the two polymers studied, PLGA is hydrophobic, whereas PLA‐PEG is hydrophilic and the drug, AZT is water‐soluble. Formulations were developed containing 10 and 25 wt % of AZT giving encapsulation efficiencies (EE) of 66 to 86% for PLGA and 90 to 94% for PLA‐PEG di‐block copolymer. All the formulations were characterized by Fourier transform spectroscopy (FTIR) to investigate the interaction of AZT with polymers and to characterize PLA‐PEG. NMR was also employed to confirm the formation of PLA‐PEG. X‐ray diffraction was used to understand the molecular level dispersion of AZT within the polymeric matrices, while differential scanning calorimetry was employed to assess thermal properties. Scanning electron microscopy was employed to understand the surface morphology of AZT‐loaded microparticles. In vitro release experiments performed in pH 7.4 buffer media extended the release of AZT up to 125 h with PLGA, whereas 30 h were required for releasing AZT through PLA‐PEG microparticles. Cumulative release data were fitted to an empirical equation to understand the nature of release characteristics. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci 000: 000–000, 2011     

Preparation of microspheres with microballoons inside for floating drug‐delivery systems

The use of floating drug‐delivery systems is one method that is used to achieve prolonged gastric residence times. We developed a novel, multiple‐unit, floating drug‐delivery system of microspheres with microballoons inside from xanthan gum (XG) and gelatin (GA) by a water‐in‐oil method. With theophylline as the model drug, four formulations (FI–FIV) with different ratios of the two polymers were prepared. The size distribution, drug‐encapsulation efficiency, floating behavior, release characteristics, and morphological properties were investigated. The ratio of the two polymers influenced the size distribution, encapsulation efficiency, and drug release appreciably. With increasing amounts of GA, the percentage yield of the floating microspheres and the drug‐encapsulation efficiency decreased from 100 and 84.5% to 31 and 56.2%, respectively. The drug‐release rate also decreased with increasing GA content, which was attributed to an increase in the crosslinking extent. An initial burst was observed, and after that, the drug was released slowly by a near‐zero‐order pattern, which was attributed to the low solubility of theophylline and the possible complexes formed by XG and GA in the simulated gastric fluid (pH 1.2). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 197–202, 2004     

Novel synthesis of ZnO nanoparticles and their enhanced anticancer activity: Role of ZnO as a drug carrier

In this work, a simple and versatile technique was developed to prepare highly crystalline ZnO nanoparticles (ZnO NPs) by organic precursor method using 5, 6 dimethyl benzimidazole and Zn(CH₃COO)₂·2H₂O followed by calcination. These synthesized ZnO NPs were used as a drug carrier to form 5-Fluorouracil (5 Fu) encapsulated ZnO NPs by varying the molar ratio (100–300:1) of ZnO NPs to 5-Fu. X-ray diffraction (XRD) results indicated that the ZnO NPs had single phase nature with the wurtzite structure. Field emission scanning electron microscopy (FESEM) and Transmission electron microscopy (TEM) results showed nanometer dimension of the NPs. FTIR analysis further reaffirmed the formation/encapsulation of ZnO NPs. UV–vis spectroscopy determined the encapsulation efficiency (EE) and loading capacity (LC) of 5-Fu drug on ZnO NPs. HPLC analysis of encapsulated NPs indicated release of 5-Fu was higher at tumor cell pH (pH 6.0) than physiological pH. Moreover, the anti-tumor activity of ZnO NPs and 5-Fu-encapsulated ZnO NPs investigated using flow cytometry demonstrated that 5-Fu encapsulated ZnO NPs have more anti-tumor activities than 5-Fu itself toward MCF-7 (Breast cancer) cell line. Also, cytotoxicity of MCF-7 increased with the increase of ZnO NPs: 5-Fu ratio. This research will introduce a new concept to synthesize 5-fluorouracil encapsulated ZnO NPs and its application towards the cancer cell line. Thus, the ZnO NPs could not only apply as the drug carrier to deliver 5-Fluorouracil into the cancer cells, but also enhances anti-tumor activity.     

Development of pH‐sensitive nanogels for cancer treatment using crosslinked poly(aspartic acid‐graft‐imidazole)‐block‐poly(ethylene glycol)

pH‐sensitive nanogels (NGs) based on poly(aspartic acid‐graft‐imidazole)‐poly(ethylene glycol) were developed using linear PEG with different molecular weights (2000 and 4000 Da) as crosslinkers. The pH‐sensitive NGs showed reversible size changes during continuously alternating pH changes. The anticancer treatment potential of pH‐sensitive NGs was studied using a model drug, irinotecan (IRI). IRI‐loaded NGs (ILNs) showed different drug release kinetics in acidic versus neutral pH, in addition to pH‐dependent cytotoxicity. Due to its longer crosslinker, ILN 4 (crosslinked with PEG 4000) showed faster IRI release and a greater magnitude of IRI release than ILN 2 (crosslinked with PEG 2000), resulting in greater cytotoxicity against HCT 116 colorectal cancer cells. These pH‐sensitive NGs could potentially be used in cancer treatment by mediating the accumulation and release of IRI from ILNs in the acidic tumor environment and by reducing systemic toxicity due to reversible swelling–shrinkage. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46268.     

Preparation and drug‐release behavior of 5‐fluorouracil‐loaded poly(lactic acid–4‐hydroxyproline–polyethylene glycol) amphipathic copolymer nanoparticles

Poly(lactic acid–4‐hydroxyproline–polyethylene glycol) (PLA–Hpr–PEG) was synthesized via melt copolymerization with stannous chloride as a catalyst activated by a proton acid. Copolymers with different poly(ethylene glycol) (PEG) concentrations (0.1, 0.5, 1, and 5 wt %) were synthesized and exhibited moderate molecular weights (weight‐average molecular weight = 9705–13,600 g/mol) and reasonable molecular weight distributions (weight‐average molecular weight/number‐average molecular weight = 1.35– 1.66). The structure of the polymers was verified with infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. The nanoparticles were made by the nanoprecipitation method with PLA–Hpr–PEG. The size and size distribution of the nanoparticles were investigated with laser light scattering, and the surface morphology of the nanoparticles was investigated with transmission electron microscopy. The drug encapsulation efficiency and drug loading content were measured with ultraviolet absorption spectroscopy. The effects of various formulation parameters were evaluated. The prepared nanoparticles were spherical and greater than 100 nm in size. The drug loading content and encapsulation efficiency were greatly influenced by the amount of the copolymer and the volume of the solvent. The PEG content in the polymer could affect the release of drugs from the PLA–Hpr–PEG nanoparticles. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2654–2659, 2007     

Preparation of poly(ethylene glycol)/chitosan membranes by a glucose‐mediating process and in vitro drug release

Novel pH‐dependent chitosan/poly(ethylene glycol) (PEG) membranes were developed for oral drug delivery. The preparation of these membranes involved a solution‐mediating process with glucose addition at different pHs. Fourier transform infrared/attenuated total reflectance showed that the Schiff‐base reaction was favored at high pHs and high glucose concentrations. X‐ray diffraction analysis showed a continuous increase in the glucose addition transformed the chitosan/PEG samples into amorphous polymers. The equilibrium swelling measurements showed that the swelling ratio of the solution‐mediated membranes decreased as the glucose concentration increased, and this was demonstrated by degree‐of‐mediation analysis. The glucose‐mediated membranes had different degrees of mediation, which depended on the pH and glucose concentration. The in vitro release profiles of theophylline‐loaded, pH 6 treated, glucose‐mediated membranes showed that the theophylline release decreased as the glucose concentration increased. Also, the release behavior of the theophylline from the glucose‐mediated membranes varied with the pH of the release medium, the glucose concentration, and the final pH of the glucose‐mediated chitosan/PEG gels. Chitosan/PEG membranes prepared by a basic glucose‐mediated process could lead to successful applications in localized drug delivery to the intestine. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1083–1094, 2005     

Encapsulation of diclofenac sodium with acidic copolymer hydrogels based on PEG/poly(N‐isopropylacrylamide‐co‐2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) semi‐interpenetrating network using in situ loading technique

A pH‐ and temperature‐responsive semi‐interpenetrating copolymer PEG6000/poly(NIPA‐co‐AMPS) (PEG/AMPS‐co‐NIPA SIPN), for short PEG SIPN, was made by ammonium persulfate‐initiated suspension copolymerization of N‐isopropylacrylamide, 2‐acrylamido‐2‐methylpropanesulphonic acid, and N,N′‐methylene‐bis‐acrylamide (MBAA; crosslinker) in the presence of PEG6000. The PEG SIPN copolymer matrices containing nanostructures made in the high‐temperature copolymerization resulted in channels for PEG and facile migration of drugs. In drug encapsulation or drug‐loading process, one can easily ignore or pay less attention to the interaction between a drug and its encapsulation materials; however, the ignored interactions may induce problems in drug properties or the release behavior in use. Sodium diclofenac (DFNa) precipitates as the carboxylic acid form in an acidic environment, and it is challenging to encapsulate sodium diclofenac in such an acidic matrix without precipitation of the sparingly soluble acid form of DFNa on the surface of the polymer substrate. To avoid bulky precipitation in drug loading, an in situ loading technique was developed for producing gel spheres with DFNa uniformly distributed in the polymer matrix. The technique is based on fast polymerization of spherical droplets of a pregel solution in which the drug is dissolved. Diffusion‐loading prodrugs were made in comparison with in situ loading prodrugs in thermal, release kinetics, and release behavior. Drug release profiles (in pH 7.4 phosphate buffer) show that the new drug loading technique gives controlled release during a period of about 7 days at 37°C. By contrast, gel spheres loaded with sodium diclofenac using the conventional diffusion technique produced almost total release of the drug within about 24 h. The thermal stability of sodium diclofenac, the PEG/AMPS‐co‐NIPA SIPN, and the prodrugs made with the SIPN and sodium diclofenac was studied. A near zero‐order release kinetics was found in the in vitro release of sodium diclofenac with in situ loading PEG SIPN prodrug. We have, for the first time, studied sodium diclofenac release behavior from the PEG SIPN hydrogel systems. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and release behavior of carboxymethylated chitosan/alginate microspheres encapsulating bovine serum albumin

Microspheres were prepared from carboxymethylated chitosan (CM‐chitosan) and alginate by emulsion phase separation. Their structure and morphology were characterized with IR spectroscopy and scanning electron microscopy. Bovine serum albumin (BSA) was encapsulated in the microspheres to test the release behavior. The swelling behavior, encapsulation efficiency, and release behavior of BSA from the microspheres at different pHs and with a pH‐gradient condition were investigated. The BSA encapsulation efficiency was calculated to be 80%. The degree of swelling of the microspheres without BSA loaded at pH 7.2 was much higher than that at pH 1.0. The encapsulated BSA was quickly released in a Tris–HCl buffer (pH 7.2), whereas a small amount of BSA was released under acid conditions (pH 1.0) because of the strong electrostatic interaction between ? NH₂ groups of CM‐chitosan and ? COOH groups of alginic acid and a dense structure caused by a Ca²⁺ crosslinked bridge. For the simulation of the processing of the drug under the conditions of the intestine, the microspheres were tested in a pH‐gradient medium, in which an acceleration of the release occurred at pH 7.4 after a lag time at a low pH (5.8–6.8). At pH 7.4, a large amount of BSA was released from the microspheres in a short time because of the rapid swelling of the microspheres. However, the release only depended on the diffusion of BSA at relatively low pHs, this resulted in a relatively low release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 878–882, 2004     

Investigation on preparation and protein release of biodegradable polymer microspheres as drug‐delivery system

Among the different approaches to achieve protein delivery, the use of polymers, especially biodegraded, holds great promise. This work aimed to study the preparation and protein release of a novel drug‐delivery system based on human serum albumin (HSA) encapsulated into biodegradable polymer microspheres. The microspheres containing HSA were elaborated by the solvent‐extraction method based on the formation of multiple w/o/w emulsion. The encapsulation efficiency (E.E.) of HSA was determined by the CBB method. Alginate/alginate and calcium chloride was added into an internal aqueous phase to investigate the protein loading efficiency, protein stability, and in vitro release profiles. Microspheres were characterized in terms of their morphology, size distribution, loading efficiency, and in vitro protein release. SDS–PAGE results showed that HSA kept its structural integrity during the encapsulation and release procedure. In vitro studies indicated that the microspheres with alginate added in the internal aqueous phase had a smaller extent of burst release. In conclusion, the work presents a new approach for macromolecular drugs (such as protein drugs, vaccines, and peptide drugs) delivery. © 2002 John Wiley & Sons, Inc. J Appl Polym Sci 84: 778–784, 2002; DOI 10.1002/app.10327     

Characterization of molecular interaionic and intraionic crosslinkable sulfonated poly(ether ether ketone‐alt‐benzimidazole) membrane

Lysozyme-loaded polymeric composite microparticles were successfully coprecipitated by solution-enhanced dispersion by supercritical CO₂ (SEDS), starting with a homogeneous organic solvent solution of lysozyme/poly(L -lactide)/poly(ethylene glycol) (lysozyme/PLLA/PEG). The effects of different drug loads (5, 8, and 12% w/w), PLLA Mw (10, 50, 100, and 200 kDa), PEG contents (0, 10, 30, and 50% PEG/(PLLA+PEG) w/w), and PEG Mw (400, 1000, and 4000 kDa) on the surface morphology, particle size, and drug release profile of the resulting composite microparticles were investigated. The results indicate that the size of the microparticles decreased and the rate of drug release increased with an increase in drug load, PEG content, or PEG Mw; the particle size first increased and then decreased with an increase in PLLA Mw, and the drug release was controlled by both particle size and PLLA Mw. The Fourier transform infrared spectrometer analysis and circular dichroism spectra measurement reveal that no significant changes occurred in the molecular structures during the SEDS processing, which is favorable to the production of protein–polymer composite microparticles for a protein drug delivery system. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

A novel gastric release PEG‐enclatherated polymethacrylate‐based memblet system

A novel polymethacrylate‐based membranous system referred to as a “memblet” was developed for potential application in controlled gastric drug delivery. A polymethacrylate‐based latex, Eudragit® E100, was enclatherated with a 60% w/v and a 30% w/v solution of polyethylene glycol 4000 to form hydrogel formulations A and B, respectively. The hydrogels were subsequently compressed into memblets that were characterized for thermal, rheological, morphological, mechano‐chemical properties, and in vitro gastric drug release analysis. Molecular mechanics (MM) simulations were performed to corroborate the experimental findings. Critical yield values of 15.39 and 5.239 Pa were obtained for hydrogel A and B, respectively. The viscoelastic region was found to be <10.67 and 2.542 Pa for hydrogels A and B, respectively. The storage modulus was greater than the loss modulus for hydrogel A while the inverse was true for hydrogel B. Thermal, mechanical, and surface morphology evaluation revealed that the converse was true for the dried membrane structure with hydrogel B having superior characterization profiles than hydrogel A. Notably, the lower PEG concentration (30% w/v) displayed better characterization profiles than a higher concentration (60% w/v). Through MM simulations, desirable agreement between the theoretical and experimental results was achieved over the given concentration range of PEG. Based on the gastric drug release analysis, memblets formulated with hydrogel B displayed superior control of drug release. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Lignin‐polyethylene glycol matrices and ethylcellulose to encapsulate highly soluble herbicides

The blending of lignin with polyethylene glycol (PEG) allowed us to obtain formulations with controlled release properties in which metribuzin have been successfully trapped with encapsulation efficiency higher than 85%. Moreover, the modification of the lignin's viscoelastic properties by the addition of PEG led to obtain herbicide formulations with active ingredient contents lower than 15%, suitable for its application in soil. Fourier transformed infrared spectroscopy and differential scanning calorimetry studies indicated the compatibility between polymers and metribuzin in lignin‐based controlled release formulations (CRFs). Lignin‐based formulations were coated in a Wurster‐type fluidized‐bed equipment using ethylcellulose and dibutylsebacate. Scanning electron microscope pictures showed a homogeneous film in ethylcellulose‐coated CRFs. The kinetic release studies showed that the release rate of metribuzin was mainly controlled either by selecting the granule size of controlled release lignin‐PEG matrixes, or by changing the thickness of coating film for ethylcellulose coated CRFs. These results could help to increase the efficiency of delivery of the highly soluble herbicide metribuzin and prevent the environmental pollution derived from its use. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41422.     

Chitosan/polyethylene glycol–alginate microcapsules for oral delivery of hirudin

A mild chitosan/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as albumin and hirudin, was investigated. The polysaccharide chitosan was reacted with sodium alginate in the presence of calcium chloride to form microcapsules with a polyelectrolyte complex membrane. Hirudin-entrapped alginate beads were further surface coated with polyethylene glycol (PEG) via glutaraldehyde functionalities. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within the initial 6 h and about 35% release of hirudin was also observed during treatment with 0.1 M HCl, pH 1.2 for 4 h. But acid-treated capsules had released almost all the entrapped hirudin into Tris-HCl, pH 7.4 media within 6 h. From scanning electron microscopic and swelling studies, it appears that the chitosan and PEG have modified the alginate microcapsules and subsequently the protein release. The microcapsules were also prepared by adding dropwise albumin-containing sodium alginate mixture into a PEG– CaCl₂ system. Increasing the PEG concentration resulted in a decrease rate of albumin release. The results indicate the possibility of modifying the formulation to obtain the desired controlled release of bioactive peptides (hirudin), for a convenient gastrointestinal tract delivery system. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 70: 2143–2153, 1998     

Formation of microcapsules of medicines by the rapid expansion of a supercritical solution with a nonsolvent

The rapid expansion from a supercritical solution with a nonsolvent (RESS‐N) was applied to the formation of polymeric microcapsules containing medicines such as p‐acetamidophenol, acetylsalicylic acid, 1,3‐dimethylxanthine, flavone, and 3‐hydroxyflavone. A suspension of medicine in carbon dioxide (CO₂) containing a cosolvent and dissolved polymer was sprayed through a nozzle to atmospheric pressure. The pre‐expansion pressure was 10–25 MPa, and the temperature was 308–333 K. The polymers were poly(L ‐lactic acid) (molecular weight = 5000), poly(ethylene glycol) (PEG; PEG4000, molecular weight = 3000; PEG6000, molecular weight = 7500; and PEG20000, molecular weight = 20,000), poly(methyl methacrylate) (molecular weight = 15,000), ethyl cellulose (molecular weight = 5000), and PEG–poly(propylene glycol)–PEG triblock copolymer (molecular weight = 13,000). The solubilities of the polymers as coating materials and these medicines as core substance were very low in CO₂. However, the solubilities of these polymers in CO₂ significantly increased with the addition of low molecular weight alcohols as cosolvents. After RESS‐N, polymeric microcapsules were formed according to the precipitation of the polymer caused by a decrease in the solvent power of CO₂. This method offered three advantages: (1) enough of the coating polymers, which were insoluble in pure CO₂, dissolved; (2) the microparticles of the medicine were encapsulated without adhesion between the particles because a nonsolvent was used as a cosolvent and the cosolvent remaining in the mixture was removed by the gasification of CO₂; and (3) the polymer‐coating thickness was controlled with changes in the feed composition of the polymer for drug delivery. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 742–752, 2003     

卡维地洛滴丸的制备工艺与表征

本文开发了一种可提高新剂型的可提高难溶性药物卡维地洛溶出的制备方法并进行表征。采用固体分散技术法制备滴丸，通过响应面试验法，按照归一值法优化指标，优选最佳工艺并验证，考察自制滴丸体外溶出度。采用差示扫描量热法（DSC）、粉末 X射线衍射法和红外吸收光谱法鉴定药物在滴丸中的存在状态。结果表明：最优制备工艺为卡维地洛与基质质量比为1∶7，PEG6000与PEG4000质量比为1∶3，滴速为54min^-1，药液温度为75℃，所建模型显著。滴丸在pH1.2的盐酸溶液中30min内释药最快，达到90%以上，其次为pH4.5、pH6.8、去离子水。所制3批滴丸重现性好，体外溶出相似（f ₂>85），稳定性好。药物在滴丸中主要以无定形状态存在，可提高难溶性药物的溶出，为卡维地洛新的口服速释剂型的开发提供参考。     

Formulation of lavandin essential oil with biopolymers by PGSS for application as biocide in ecological agriculture

Essential oils, and in particular lavandin (lavandula hybrida) essential oil, can be used as natural biocides as an alternative to synthetic chemical biocides. For this purpose, agrochemical formulations of the essential oils should be physically stable in the long term and should enhance the biological performance of the agrochemical. In this work, such a formulation of lavandin essential oil obtained by encapsulation of the oil in a biodegradable polymer has been studied. Two high-pressure precipitation techniques, particles from gas saturated solutions (PGSS) and PGSS-drying, have been applied to perform the encapsulation. The PGSS process has been used to encapsulate the oil in polyethylene glycol (PEG). With PGSS-drying the oil has been encapsulated in n-octenyl succinic (OSA)-modified starches, by removing the water form an oil-in-water emulsion stabilized using the OSA-starches as surfactants. Operating conditions were selected in order to reduce oil losses due to its dissolution in supercritical CO₂ or due to emulsion destabilization. A comparison between the characteristics of the particles obtained by encapsulation in PEG with PGSS and by encapsulation in OSA-starches with PGSS-drying was done. Results revealed that encapsulation efficiencies of lavandin oil were higher in PEG microcapsules obtained by PGSS (14-66% of initial oil encapsulated). Particles show a spherical morphology and a narrow particle size distribution, which is favourable for a controlled release of lavandin essential oil.     

Self-assembled polymeric micelles based on THP and THF linkage for pH-responsive drug delivery

Developing smart nanocarriers for drug delivery system is advantageous for many kinds of successful biomedicinal therapy. In this study, we designed an amphiphilic block copolymers containing pH-responsive tetrahydropyran (THP) and tetrahydrofuran (THF) linkage. Their structures were confirmed by ¹H NMR and gel permeation chromatography (GPC). The release rate of encapsulated drugs depends upon the pH value and pH sensitive linkage in the backbone of copolymers. For PLA–THP–PEG micelles the cumulative release amount of doxorubicin (DOX) was 62% at pH 5.0, which is about four times higher than that at pH 7.4. Under the same conditions the release rate for PLA–THF–PEG micelles is a little faster than that of the PLA–THP–PEG micelles. Cellular uptake study demonstrates that DOX-loaded micelles can easily enter the cells and produce the desired pharmacological action and minimizing the side effect of free DOX. These findings indicate that THP and THF linked diblock copolymer micelles is a promising candidate for drug carrier.