Synthesis and characterization of an amphiphilic hyperbranched poly(amine‐ester)‐co‐D,L‐lactide (HPAE‐co‐PLA) copolymers and their nanoparticles for protein drug delivery

A series of hyperbranched poly(amine‐ester)‐co‐D ,L ‐lactide (HPAE‐co‐PLA) copolymer were synthesized by ring‐opening polymerization of D ,L ‐lactide with Sn(Oct)₂ as catalyst to a fourth generation branched poly(amine‐ester) (HPAE‐OHs4). The chemical structures of copolymers were determined by FTIR, ¹H‐NMR, ¹³C‐NMR, and TGA. Double emulsion (DE) and nanoprecipitation (NP) method were used to fabricate the nanoparticles of these copolymers encapsulating bovine serum albumin (BSA) as a model. DSC thermo‐grams indicated that the nanoparticles with BSA kept stable below 40°C. Different factors which influence on particular size and encapsulation efficiency (EE) were investigated. Their EE to BSA could reach 97.8% at an available condition. In vitro release behavior of NPs showed a continuous release after a burst release. The stability maintenance of BSA in the nanoparticle release in vitro was also measured via circular dichroism and fluorescence spectrometry. The results showed that the copolymer nanoparticles have a promising potential in protein delivery system. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis and characterization of amphiphilic pluronic (F68)‐1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphoethanolamine copolymers and their micelles as a drug carrier

A new Pluronic (F68)‐1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphoethanolamine (DPPE) (Pluronic (F68)–DPPE) copolymer was synthesized with Pluronic (F68) and DPPE. The chemical structure and physical properties of copolymers were determined by FTIR, ¹H NMR, ¹³C NMR, ³¹P NMR, and TGA. Environmental scanning electron microscopy, fluorescence spectroscopy, and dynamic light scattering method confirmed the formation of copolymeric micelles of Pluronic (F68)‐DPPE. To estimate the feasibility as novel drug carriers, the copolymer micelles were prepared by the phase separation dialysis method. Amphotericin B as a lipophilic model drug was incorporated into copolymeric micelles and the drug release behavior was investigated. It was found that the chemical composition of the micelle was a key factor in controlling micelles size, drug‐loading content, and drug release behavior. As DPPE segment weight ratio increased, the micelle size and drug‐loading content increased, and the drug release rate decreased. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation and drug release behaviors of 5‐fluorouracil loaded poly(glycolide‐co‐lactide‐co‐caprolactone) nanoparticles

5‐Fluorouracil (5‐Fu) loaded poly(glycolide‐co‐lactide‐co‐caprolactone) (PGLC) nanoparticles were prepared by modified spontaneous emulsification solvent diffusion method (modified‐SESD method) and characterized by dynamic light scattering, scanning electron microscopy and ¹H NMR determination. It was found that the obtained nanoparticles showed near spherical shape and was controllable with the radius range of 30–100 nm. Compared with the nanoparticles prepared by polylactide and poly (lactide‐co‐glycolide) (PLGA) under the similar preparation condition, yield of PGLC nanoparticles was the highest, which reached to about 100%. On the other hand, drug entrapment efficiency of PGLC nanoparticles was also higher than that of PLGA and PLLA nanoparticles. 5‐Fu release behavior of PGLC nanoparticles in vitro showed that 5‐Fu release of PGLC nanoparticles showed a near zero‐order release profile, and 5‐Fu release rate of PGLC nanoparticles was faster than that of PLLA and PLGA nanoparticles. According to degradation behavior of PGLC nanoparticles, it could be proposed that the kinetic of degradation controlled release played an important role in the release process of PGLC nanoparticles. It revealed that the PGLC nanoparticles could be a promising drug carrier. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Preparation and evaluation of novel blend microspheres of poly(lactic‐co‐glycolic)acid and pluronic F68/127 for controlled release of repaglinide

The objective of the present work was to study the release behavior of plain and blend microspheres (MS) of PLGA and Pluronic F68/127. In this study, a novel blend MS of poly(D ,L ‐lactic‐co‐glycolic acid) (PLGA) and Pluronic F68/127 (PLF68/127) were prepared by the emulsion–solvent evaporation method. Repaglinide, an antidiabetic drug with a very short half‐life, was successfully encapsulated into the blend MS. Various formulations were prepared by varying the ratio of PLGA and PLF68/127. Drug encapsulation up to 91% was achieved as measured by UV spectroscopy. Scanning electron microscopy showed that MS have smooth surfaces even after incorporation of PLF68/127. Particle size, as measured by using laser light scattering technique, gave an average size ranging from 12 to 47 μm. Differential scanning calorimetry (DSC) was performed to understand the crystalline nature of the drug after encapsulation into MS. DSC revealed the crystalline dispersion in the polymer matrix. In vitro release experiments performed in simulated intestinal fluid, indicated the dependence of release rate on the amount of PLF68/127 present in the MS; slow release was extended up to 153 h. Release data have been fitted to an empirical equation to compute the diffusional exponent (n), which indicated that the release mechanism to be non‐Fickian type. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation of poly(DL‐lactide‐co‐glycolide) nanoparticles without surfactant

The preparation of poly(DL ‐lactide‐co‐glycolide) (PLGA) nanoparticles was performed by a dialysis method without surfactant or emulsifiers. The size of the PLGA nanoparticles prepared from dimethylacetamide (DMAc) as an initial solvent was smaller than that from acetone. The sizes of the PLGA nanoparticles from DMAc and acetone were 200.4 ± 133.0 and 642.3 ± 131.1 nm, respectively. The effects of the initial solvent selected to dissolve the copolymer and the lactide:glycolide ratio were investigated. The PLGA nanoparticles were spherical as revealed by the results of scanning electron microscopy and transmission electron microscopy observations. From these results it was shown that PLGA nanoparticles could be formed by the dialysis method without surfactant. The drug‐loading contents and efficiency were also dependent on the lactide:glycolide ratio and initial feeding amount of the drug. A higher lactide ratio resulted in higher drug loading and higher loading efficiency. However, a higher initial feeding amount of the drug resulted in higher drug loading and lower loading efficiency. Clonazepam was released for at least 2 days and the release rate was slower with a higher lactide:glycolide ratio and a larger amount of drug‐loading nanoparticles than that with a lower lactide:glycolide ratio and a smaller amount of drug‐loading nanoparticles. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 2228–2236, 2001     

Surfactant‐free nanoparticles of poly(DL‐lactide‐co‐glycolide) prepared with poly(L‐lactide)/ poly(ethylene glycol)

Surfactant‐free nanoparticles of poly(DL ‐lactide‐co‐glycolide) (PLGA) nanoparticles were prepared with or without poly(L ‐lactide)‐poly(ethylene oxide) (LE) diblock copolymer (abbreviated as PLGA/LE and PLGA nanoparticles) by dialysis method. LE diblock copolymer was used to make PLGA nanoparticles to alternate conventional surfactant. The size of PLGA and PLGA/LE nanoparticles was 295.3 ± 171.3 and 307.6 ± 27.2 nm, respectively, suggesting LE diblock copolymer might be coated onto the surface of nanoparticles. Observation of scanning electron microscope (SEM) showed that PLGA/LE nanoparticles have spherical shapes ranging ～ 200–500 nm. In ¹H‐NMR study, characteristic peaks of the methyl protons of PLGA disappeared in D₂O, whereas characteristic peaks of the methyl proton of both PEG and PLGA were shown in both CDCl₃ and D₂O, indicating that LE diblock copolymer coated on the surface of the PLGA nanoparticles. The higher the initial content of drug, the higher the drug contents and the lower the loading efficiency. PLGA/LE nanoparticles at higher drug contents resulted in slower adriamycin·HCl (ADR) release rate than that of lower drug contents. Also, slower release rate of ADR was achieved by entrapped into the PLGA/LE nanoparticles, whereas LE polymeric micelles showed rapid ADR release. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1116–1123, 2003     

Ethylenediamino bridged bis(β‐cyclodextrin)/ poly(DL‐lactic‐co‐glycolic acid) nanoparticles prepared by modified double emulsion method: Effect of polyvinyl alcohol on nanoparticle properties

This study continues long‐standing efforts to develop protein delivery systems based on cyclodextrin‐conjugated polyester in our laboratory. The crude products of ethylenediamino bridged bis(β‐cyclodextrin)‐conjugated poly(DL ‐lactic‐co‐glycolic acid) were used in this study to make full use of unreacted reactant. With bovine serum albumin (BSA) as a model protein, the encapsulation effects (the encapsulation efficiency and particle size) of nanoparticles were similar to those of using pure conjugated products. Besides, a water‐in‐oil‐in‐water emulsification technique was conveniently modified. By adding polyvinyl alcohol (PVA) in the internal aqueous phase, a more stabilized emulsion was formed. Consequently, less PVA (～ 0.05%) was needed in the outer aqueous phase and less PVA (0.14 g/g nanoparticles) remained in the nanoparticles. This modification resulted in improved encapsulation efficiency (～ 89–94%) of BSA and an enlarged particle size (340–390 nm). Furthermore, the burst release of BSA at the 1st day was less pronounced (7–12% of the encapsulated amount) than that of nanoparticles with no PVA added in the internal aqueous phase. Degradation studies using transmission electron microscope and gel permeation chromatography suggested that the mechanism for protein release was mainly through nanoparticles erosion. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Micelles formed by self‐assembly of hyperbranched poly[(amine‐ester)‐co‐(D,L‐lactide)] (HPAE‐co‐PLA) copolymers for protein drug delivery

BACKGROUND: The aim of the work presented was to synthesize a series of amphiphilic hyperbranched poly[(amine‐ester)‐co‐(D ,L ‐lactide)] (HPAE‐co‐PLA) copolymers and study the formation of copolymeric micelles. These copolymeric micelle systems are expected to be potential candidates for applications in protein drug delivery. RESULTS: The chemical structures of the copolymers were confirmed by Fourier transform infrared spectroscopy, ¹³C NMR and thermogravimetric analysis. Fluorescence spectroscopy and dynamic light scattering confirmed the formation of copolymeric micelles of the HPAE‐co‐PLA copolymers. The maintenance of stability of bovine serum albumin (BSA) during release from micelles in vitro was also measured using circular dichroism and fluorescence spectrometry. CONCLUSION: Novel hyperbranched HPAE‐co‐PLA copolymers have been synthesized. Conjugation of PLA to HPAE was proved to be an available method for the preparation of micelles for protein delivery. The BSA‐loaded micelles showed enhanced encapsulation efficiency and the structural stability of BSA was retained during the release process. The hyperbranched polymeric micelles could be useful as drug carriers for protein drug delivery systems. Copyright © 2008 Society of Chemical Industry     

Thermosensitive nanoparticles prepared from poly(N‐isopropylacrylamide‐acrylamide‐vinilpyrrolidone) and its blend with poly(lactide‐co‐glycolide) for efficient drug delivery system

Temperature‐responsive polymers have become increasingly attractive as carrier for the injectable drug delivery systems. In the present work, we have studied the preparation of poly(N‐isopropylacrylamide‐acrylamide‐vinilpyrrolidone) (NIPAAm‐AAm‐VP terpolymer) nanoparticulated terpolymer and its blend with poly(lactide‐co‐glycolide, PLGA; molar ratio of lactide/glycolid 1/3). Thermosensitive terpolymer, poly(NIPAAm‐AAm‐VP) was prepared by free‐radical polymerization in aqueous solution. The nanoparticles of poly(NIPAAm‐AAm‐VP) and its blend with PLGA containing naltrexone were prepared using the evaporation and w/o emulsion‐solvent evaporation methods, respectively. Nanoparticles prepared from terpolymer‐PLGA blend at low polymer concentration (5%) shows larger particle size (>300 nm) and higher drug content%. Various types of nanoparticles showed a burst release of less than 10% after 24 h . The results suggest that by regulating different variables, desired release profiles of naltrexone can be achieved using a blend of PLGA‐poly(NIPAAm‐AAm‐VP) nanoparticulate system. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Fabrication and properties of core‐shell structure P(LLA‐CL) nanofibers by coaxial electrospinning

In this article, core‐shell structure nanofibers were fabricated by coaxial electrospinning with biodegradable copolymer Poly(L ‐Lactic‐ε‐Caprolactone) [P(LLA‐CL) 50 : 50] as shell and bovine serum albumin (BSA) as core. Morphology and microstructure of the nanofibers were characterized by scanning electron microscopy and transmission electron microscopy. The mechanical properties were investigated by stress‐strain tests. In vitro degradation rates of the nanofibrous membranes were determined by measuring their weight loss when immersed in phosphate‐buffered saline (pH 7.4) for a maximum of 14 days. Release behavior of BSA was measured by an ultraviolet‐visible spectroscopy, and the results demonstrated that BSA could release from P(LLA‐CL) nanofibers in a steady manner. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Application of the biodegradable diblock copolymer poly(L‐lactide)‐block‐poly(L‐cysteine): Drug delivery and protein conjugation

A novel approach to self‐assembled and shell‐crosslinked (SCL) micelles from the diblock copolymer poly(L ‐lactide)‐block‐poly(L ‐cysteine) to be used as drug and protein delivery carriers is described. Rifampicin was used as a model drug. The drug‐loaded SCL micelles were obtained by self‐assembly of the copolymer in the presence of the drug in aqueous media. Their morphology and size were studied with dynamic light scattering and field emission scanning electron microscopy. The rifampicin loading capacity and encapsulation efficiency were studied with ultraviolet–visible spectrophotometry. The drug‐release rate in vitro depended on the oxidizing and reducing environment. Moreover, a straightforward approach to the conjugation of the copolymer with bovine serum albumin (BSA) was developed, and a gel electrophoresis test demonstrated that this conjugated BSA could be reversibly released from the copolymer substrate under reducing conditions. In conclusion, this L ‐cysteine copolymer can be used in drug delivery and in protein fixation and recovery. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Intrinsic factor and vitamin B12 complex‐loaded poly[lactic‐co‐(glycolic acid)] microspheres: preparation,characterization and drug release

BACKGROUND: Vitamin B12 is an essential vitamin required by all mammals. Absorption of vitamin B12 is facilitated by binding of intrinsic factor–vitamin B₁₂ complex to specific receptors in the ileum. In humans a deficiency of this vitamin or a lack of intrinsic factor leads to pernicious anaemia. The major objective of the present study was to prepare intrinsic factor–vitamin B12 complex‐loaded poly[lactic‐co‐(glycolic acid)] (PLGA)‐based microparticles and to investigate their release kinetics. RESULTS: PLGA copolymer was synthesized by the ring‐opening polymerization method and characterized using gel permeation chromatography, Fourier transform infrared spectroscopy and ¹H NMR. The glass transition temperature measurement showed a single T_g at 40 °C. The intrinsic factor–vitamin B12 complex‐loaded PLGA microspheres were prepared by a water‐in‐oil‐in‐water double emulsion solvent extraction/evaporation technique. An environmental scanning electron microscopy investigation demonstrated that the PLGA particles had a mean particle diameter of 38 µm. Interestingly, different drug release patterns (bi‐ and triphasic ones) were observed for vitamin B12‐loaded and intrinsic factor–vitamin B12 complex‐loaded microspheres. In contrast to the rapid release of vitamin B12 by itself, in vitro release tests showed that intrinsic factor and vitamin B12 in the complex were released from PLGA microspheres in a sustained manner over 15 days. CONCLUSION: PLGA microspheres can be an effective carrier for the intrinsic factor–vitamin B12 complex. Copyright © 2007 Society of Chemical Industry     

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     

Synthesis of chitosan‐graft‐β‐cyclodextrin for improving the loading and release of doxorubicin in the nanopaticles

Chitosan‐graft‐β‐cyclodextrin (CS‐g‐β‐CD) copolymer was synthesized by conjugating β‐cyclodextrins to chitosan molecules through click chemistry. The copolymer structure was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). CS‐g‐β‐CD/CMC nanoparticles were prepared by a polyelectrolyte complexation process in aqueous solution between CS‐g‐β‐CD copolymer and carboxymethyl chitosan (CMC), which was used to load anticancer drug (Doxorubicin hydrochloride, DOX·HCl) with hydrophobic group. The particle size, surface charge, zeta potential, and morphology of the nanoparticles were characterized with dynamic light scattering. The drug loading efficiency and in vitro release of DOX·HCl of the nanoparticles were measured by ultraviolet spectrophotometer. The results demonstrated that the size, surface charge and drug loading efficiency of the nanoparticles could be modulated by the fabrication conditions. The drug loading efficiency of CS‐g‐β‐CD/CMC nanoparticles was improved from 52.7% to 88.1% because of the presence of β‐CD moieties with hydrophobic cavities, which can form inclusion complexes with the drug molecules. The in vitro release results showed that the CS‐g‐β‐CD/CMC nanoparticles released DOX·HCl in a controlled manner, importantly overcoming the initial burst effect. These nanoparticles possess much potential to be developed as anticancer drug delivery systems, especially those drugs with hydrophobic group. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41034.     

PCL/poloxamer 188 blend microsphere for paclitaxel delivery: Influence of poloxamer 188 on morphology and drug release

A novel controlled release system, paclitaxel‐loaded poly (ε‐caprolactone) (PCL)/poloxamer 188 (Pluronic F68, F68) blend microspheres is proposed in the present work. F68 was incorporated into PCL matrices as both a pore‐forming agent and a drug releasing enhancer. Paclitaxel‐loaded PCL/F68 blend microspheres with different amounts of F68 were prepared by the oil‐in water (O/W) emulsion/solvent evaporation method. Characterization of the microspheres followed to examine the particle size, the drug encapsulation efficiency, the surface morphology, and in vitro release behavior. The influences of F68 on microsphere morphology and paclitaxel release are discussed. The porosity of the surface of PCL/F68 blend microspheres and the release rate of paclitaxel from the PCL/F68 blend microspheres increased as the initial amount of blended F68 increased. Faster and controlled release was achieved in comparison with the PCL microspheres. Through this study, the developed microporous PCL/F68 blend microspheres could be used as a drug delivery system to enhance and control drug release in the future. © 2007 Wiley Periodicals, Inc. JAppl Polym Sci 104: 1895–1899, 2007     

Controlled delivery of growth‐hormone‐releasing peptide 6 from the poly(lactic‐co‐glycolic acid)–poly(ethylene glycol)–poly(lactic‐co‐glycolic acid) copolymer and the effect of a growth‐hormone‐releasing peptide 6–copolymer hydrogel on the growth of rex rabbits

Growth‐hormone‐releasing peptide 6 (GHRP‐6) plays an important role in animal growth. However, there have been few studies focusing on the effect of GHRP‐6 on animal growth through controlled release systems. We synthesized the poly(lactic‐co‐glycolic acid) (PLGA)–poly(ethylene glycol) (PEG)–PLGA copolymer to investigate its controlled released effect on GHRP‐6 in vitro and to study the effect of a GHRP‐6–copolymer hydrogel on the growth of rex rabbits. The copolymer was synthesized with ring‐opening copolymerization and characterized by ¹H‐NMR. The interaction between GHRP‐6 and the copolymer was characterized by Fourier transform infrared spectroscopy and X‐ray diffraction. The body weight, serum level of insulin‐like growth factor 1 (IGF‐1), and hair coat quality were studied in rex rabbits. The results show that hydrogen bonds formed between the N? H group in GHRP‐6 and the C?O group in the copolymer. The release mechanism of GHRP‐6 was a combination of a diffusion‐controlled mechanism and an erosion‐controlled mechanism in the copolymer. The serum level of IGF‐1, hair coat quality, and body weight were all significantly higher in the GHRP‐6–copolymer hydrogel group than in the other groups. These results indicate that the copolymer effectively controlled the release of GHRP‐6. In addition, the GHRP‐6–copolymer hydrogel increased the synthesis of IGF‐1 for a prolonged period and, thereby, increased the rex rabbits' growth and hair coat quality. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40185.     

Lamotrigine‐loaded polyacrylate nanoparticles synthesized through emulsion polymerization

A series of copolymeric nanoparticles of the partially water‐soluble monomer ethyl methacrylate and the water‐soluble monomer 2‐hydroxyl ethyl methacrylate were synthesized from emulsions containing sodium dodecyl sulfate via free‐radical polymerization. Lamotrigine, as a model drug, was loaded in nanoparticles during in situ polymerization. A stable and transparent poly(ethyl methacrylate‐co‐hydroxyl ethyl methacrylate) nanolatex was produced for all compositions and characterized for particle size by dynamic light scattering and transmission electron microscopy. Particles were found to be smaller than 50 nm in size. Structural characterization of copolymers was done by infrared spectrometry, gel permeation chromatography, and NMR spectroscopy. Drug encapsulation efficiency was determined by ultraviolet (UV)–visible spectrometry and was found to be 26–62% for copolymers with different compositions. UV data suggest molecular‐level dispersion of the drug in the nanoparticles. In vitro drug‐release studies showed the controlled release of lamotrigine. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Preparation and release characteristics of dexamethasone acetate loaded organochlorine‐free poly(lactide‐co‐glycolide) nanoparticles

Dexamethasone‐loaded poly(lactide‐co‐glycolide) (PLGA) devices are commonly used as model systems for controlled release. In this study, PLGA nanoparticles containing dexamethasone acetate were prepared by a nanoprecipitation technique in the absence of organochlorine solvents and were characterized by their mean size, ζ potential, scanning electron microscopy, and differential scanning calorimetry to develop a controlled release system. The analytical method for the quantification of dexamethasone acetate by high‐performance liquid chromatography was validated. The results show that it was possible to prepare particles at a nanometric size because the average diameter of the drug‐loaded PLGA particles was 540 ± 4 nm with a polydispersity index of 0.07 ± 0.01 and a ζ potential of ?2.5 ± 0.3 mV. These values remained stable for at least 7 months. The drug encapsulation efficiency was 48%. In vitro tests showed that about 25% of the drug was released in 48 h. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41199.     

Pilocarpine‐loaded poly(DL‐lactic‐co‐glycolic acid) nanoparticles as potential candidates for controlled drug delivery with enhanced ocular pharmacological response

The poor corneal residence time of pilocarpine, an alkaloid extracted from the leaves of the Jaborandi plant, limits its ocular application. The aim of this study was to develop, characterize, and evaluate the potential of pilocarpine entrapped by poly(DL ‐lactic‐co‐glycolic acid) (PLGA) nanoparticle carriers for ocular drug delivery. Pilocarpine‐loaded nanoparticles were prepared with a double‐emulsion (water in oil in water) method and characterized with transmission electron microscopy and X‐ray diffraction analysis. The nanoparticles exhibited an average size of 82.7 nm with an encapsulation efficiency of 57%. Stability studies showed the absence of agglomeration and constancy in the amount of drug entrapped; this indicated the solidity of these particles for long‐term use. The in vitro release studies conducted in simulated tear fluid showed the sustained release of pilocarpine. In vivo evaluation of the nanoparticles was done in a rabbit model with a miosis assay and compared to an equal dose of commercially available eye drops of pilocarpine (Pilocar drops). The in vivo miosis studies showed that the duration of miotic response increased by 40% for the nanoparticles and produced an almost 68% increase in total miotic response when compared to the eye drops. In conclusion, this study clearly demonstrated the potential of pilocarpine‐loaded PLGA nanoparticles for multiplying the therapeutic effect of ophthalmic drug delivery with enhanced bioavailability and pharmacological response. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Reduction‐sensitive carrier containing disulfide bond based on Pluronic F68 with cholesterol for drug delivery

The reduction‐sensitive amphiphilic polymer chol‐SS‐F68‐SS‐Chol (F68‐CDEC. chol, SS and F68 represent cholesterol, disulfide bond and Pluronic F68, respectively) was easily synthesized by two steps of esterification reactions. The self‐assembly behavior of the polymer was studied by fluorescence spectrophotometry, dynamic light scattering and TEM. Impressively, the critical micelle concentration of F68‐CDEC was 58‐fold smaller than that of F68. Besides, the drug loading content (LC = 20.25%) was higher than that of F68 (LC = 13.42%). In vitro release experiments showed that the reductant dithiothreitol triggered rapid disintegration of micelles with an accumulated drug amount of 55%, compared with an accumulated drug amount of 20% in phosphate‐buffered saline solution. These good abilities were further proved by cell uptake experiments. More importantly, almost no cytotoxicity was observed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) colorimetric assay and immunofluorescence staining experiments. There are reasons to believe that the polymer F68‐CDEC can be used as a reduction‐sensitive drug delivery material. © 2020 Society of Industrial Chemistry