Synthesis and characterization of novel liquid crystalline cholesteryl-modified hydroxypropyl cellulose derivatives

Two new series of cholesteryl-modified hydroxypropyl cellulose (HPC) derivatives were synthesized by performing reactions involving HPC, a cholesterol-based mesogenic dimer (HPC-G1-Chol), or cholesteryl chloroformate (HPC-Chol), all with different degrees of substitution (D _Chol). All of the compounds obtained were characterized by conventional spectroscopic methods. The D _Chol values of the modified HPCs was obtained using ¹H NMR spectroscopy. Thermogravimetric analysis and differential scanning calorimetry (DSC) in combination with polarizing optical microscopy (POM) were used to investigate the thermal properties of the compounds obtained. The glass transitions of the modified HPCs occurred at lower temperatures than the glass transition temperature for HPC, but the glass transition temperatures increased with increasing D _Chol. All of the synthesized polymers formed thermotropic liquid crystalline phases. Polymers with a mesogenic side chain (i.e., the HPC-G1-Chol series) had wider mesophases than HPC and polymers that were derived from HPC-Chol. These compounds were found to be soluble in a variety of organic solvents, so they formed lyotropic liquid crystal mesophases in acetone. The critical concentrations above which liquid crystalline order was observed were 20 and 25 wt% for a sample from each series (HPC-G1-Chol and HPC-Chol, respectively) in acetone. It can therefore be hypothesized that HPC-G1-Chol has a greater propensity to exhibit specific chain–chain association phenomena than HPC-Chol in acetone.     

Thermosensitive biotinylated hydroxypropyl cellulose-based polymer micelles as a nano-carrier for cancer-targeted drug delivery

In this article, we report the synthesis of a novel amphiphilic hydroxypropyl cellulose-based polymer (HPC-PEG-Chol) that contained poly (ethylene glycol) and cholesterol-containing moieties with specific degrees of substitution. The resulting polymer was subsequently converted to a biotin conjugate (HPC-PEG-Chol-biotin), to develop a new potential cancer-targeted drug delivery system. The biotin conjugate was used to prepare micelles via the dialysis method. The polymeric micelles in aqueous solution presented a lower critical solution temperature (LCST) of 39.8 ^oC. The critical micelle concentration (CMC) values of the polymeric micelles at 25 and 45 °C were evaluated to be about 0.32 and 0. 25 g/L, respectively. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses of the micelles revealed the spherical shapes of the micelles, with 84 nm mean diameters that increased with the increase of the temperature above LCST. The hydrophobic anticancer drug paclitaxel (PTX) was loaded in the micelles and the in vitro release behaviors of PTX were investigated at different temperatures. The release profile of PTX from the polymeric micelles revealed a thermosensitivity, since its release rate was higher at 41 °C than at 37 °C. Fluorescent microscopy analyses confirm that the PTX-loaded HPC-PEG-Chol-biotin is superior in cellular uptake, with very strong adsorption to both HeLa and MDA-MB-231 cancer cell lines. MTT assay in normal cells indicated that HPC-PEG-Chol-biotin micelles have great potential to be safely used in tumor-targeting chemotherapy.     

Thermosensitive micelles from PEGylated oligopeptides

New thermosensitive and micelle-forming diblock copolymers were synthesized by amide coupling of carboxylated methoxy-poly(ethylene glycols) with hydrophobic oligopeptides and characterized by means of ¹H NMR spectroscopy, elemental analysis, and dynamic light scattering (DLS) measurements. Stable micelles were formed from copolymers composed of MPEG550 or MPEG750 as a hydrophilic segment and the hexapeptide, GlyPheLeuGlyPheLeuEt, as a hydrophobic segment. All the present diblock copolymers exhibited thermosensitive properties by showing a lower critical solution temperature (LCST) in water. The LCST of the copolymers composed of relatively shorter MPEG350 and GlyPheLeuAspEt₂ was observed at much higher temperature (48 °C) compared with the LCST (29 °C) of the cyclotriphosphazene analogues bearing the same hydrophilic and hydrophobic segments as side groups. The remarkably lower LCST of the cyclotriphosphazene analogue is presumed to be due to the structural effect of the cis-nongeminal conformation of its three hydrophobic oligopeptides, but such a structural effect was found to diminish as the chain lengths of the hydrophilic and hydrophobic blocks of the copolymers increased.     

Dual-responsive semi-IPN copolymer nanogels based on poly (itaconic acid) and hydroxypropyl cellulose as a carrier for controlled drug release

Dual-responsive nanogels were prepared by polymerization of itaconic acid (IA) and copolymerization with methacrylic acid (MA) in aqueous solution of hydroxypropyl cellulose (HPC) and cross-linking with N, N′-methylenebisacrylamide (MBAm) through an easy and green process. FTIR spectroscopy, TEM, AFM, DLS and zeta potential studies confirmed the semi-interpenetrating (semi-IPN) polymer network structure of nanogels. The LCST of HPC was increased to a higher temperature than HPC’s intrinsic LCST, while the presence of the MA comonomer improved the hydrophobicity of the copolymer and reduced LCST to about body temperature and suppressed the excessive nanogel aggregation. It was found that the concentration of reactants impacted the process of nanogel formation. Additionally, an increasing of cross-linker concentration led to a reduced size of HPC nanogels. Besides, the diameter of nanogels was changed with the temperature and pH. TEM and AFM photographs of copolymer nanogels illustrated that the nanoparticles with small diameters (<100 nm) were prepared. With loading the doxorubicin into the copolymer nanogels, the particle size became larger (about 150 nm) and due to the electrostatic interaction of the cationic drug with anionic particles, the zeta potential was increased. Drug release processes were followed at pH = 5.0 and 7.4 and with 37- and 41-°C temperatures, respectively. The maximum in-vitro release studies of drug-loaded nanogels, which is 91% for the pH 5.0 buffer solution at 41 °C, demonstrated the temperature- and pH-sensitivity of prepared copolymer nanogels.     

Study on glucose release ability from hydroxypropyl cellulose films

Polymer Bulletin - Drug delivery systems based on different glucose and hydroxypropyl cellulose (HPC) ratios were prepared and characterized to check their suitability as controlled drug delivery...     

ABC block copolymer as “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs

Amphiphilic triblock copolymer of poly(ethylene glycol)-block-poly(dimethylaminoethyl methacrylate)-block-poly(ε-caprolatone) (PEG-PDMA-PCL) was synthesized using a one-pot sequential oxyanionic polymerization of DMA and ε-CL, associated with a PEG-O⁻K⁺ macroinitiator. The pH-responsive micellization behavior of the copolymer was studied using dynamic light scattering (DLS), steady-state fluorescence and TEM techniques. The anti-cancer drug of doxorubicin (DOX) was chosen as a model drug to investigate the potential application of this triblock copolymer in drug controlled release. The results indicated the important roles of the PCL block for drug loading, the PDMA block for pH-responsive release, and PEG block for good bio-affinity. Cell cytotoxicity tests showed that the DOX-loaded PEG-PDMA-PCL micelles were pharmaceutically active to suppress the growth of SKOV-3 cells. This novel stimuli-responsive block copolymer is an attractive candidate as the “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs.     

低取代羟丙基纤维素的溶解性及其表征方法

采用偏光显微镜、旋转黏度计和广角X射线衍射仪表征了低取代羟丙基纤维素(HPC)在氢氧化钠水溶液中的溶解性能。结果表明:在质量分数为8%的NaOH溶液中,-5℃下可以较好地溶解HPC,高相对分子质量HPC溶解性较差,而低相对分子质量HPC溶解性较好,且动力黏度小;彩色偏光显微照片中紫红色背景区域意味着HPC大分子链呈胶束状溶解分散状态(即尚未充分溶解),充分溶解的HPC溶液则呈现淡蓝色的背景颜色,而未溶解且保持纤维状的HPC则可能呈现红、黄和蓝三色;偏光显微镜法和旋转黏度计法可以用来表征HPC的溶解性,X射线衍射法则不适宜表征其溶解性。     

Phase studies of a liquid crystalline polymer: hydroxypropyl cellulose

Phase diagrams for the isotropic-anisotropic phase transition in solutions of a thermotropic cellulose derivative, hydroxypropyl cellulose are presented. The effect of the molecular weight is demonstrated. A comparison to the theory of semi-rigid liquid crystalline polymers is given.     

In situ gel forming systems of poloxamer 407 and hydroxypropyl cellulose or hydroxypropyl methyl cellulose mixtures for controlled delivery of vancomycin

Poloxamers are a family of triblock copolymers consisting of two hydrophilic blocks of polyoxyethylene separated by a hydrophobic block of polyoxypropylene, which form micelles at low concentrations and form clear thermally reversible gels at high concentrations. The objective of this study was to develop an in situ gel forming drug delivery system for vancomycin using the minimum possible ratio of poloxamer 407 (P407). Decreasing the concentration of poloxamer could reduce the risk of hypertriglyceridemia induction. Different additives were added to the poloxamer formulations. It was observed that among different additives, hydroxypropyl methyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) can decrease poloxamer concentration required to form in situ gelation from 18 to 10%. The dynamic viscoelastic properties of the samples were determined. Both the storage modulus and the loss modulus of the samples increased abruptly as the temperature passed a certain point. The gelling temperature was in the order of P407 : HPC (10 : 10 w/w) < P407 : HPMC (10 : 10 w/w) < P407 : HPMC (15 : 5 w/w) < P407 : HPC (15 : 5 w/w). Drug release rate could be controlled by changing the type and ratio of additives as well as the amount of drug loaded. It can be concluded that combining P407 and cellulose derivatives could be a promising strategy for preparation of thermally reversible in situ gel forming delivery systems with low poloxamer concentration. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Die swell of liquid crystal-forming solutions of hydroxypropyl cellulose through a long capillary die

The die swell and shear viscosity of lyotropic liquid crystal-forming hydroxypropyl cellulose solutions in N,N-dimethylacetamide were determined over a relatively wide range of shear stress or polymer concentration at 30°C by using a long capillary die with an aspect ratio of 114. The dependence of die swell on the concentration was similar to that of shear viscosity: a maximum at a critical concentration C_a and a minimum at another critical concentration C_b (C_a < C_b). The dependence of the swell on shear stress is greatly affected by the solution phase: in an isotropic range (below C_a), the die swell increased monotonously with shear; in the vicinity of C_a, the die swell exhibited a maximum; in a biphasic range (between C_a and C_b), the die swell decreased monotonously; in a single-phase anisotropic range (above C_b), the die swell exhibited a minimum. Above C_b, extrudate distortion was observed and disappeared around the shear where the die swell exhibited a minimum.     

Nonisothermal crystallization kinetics of PLA/nanosized YVO4 composites as a novel nucleating agent

The influence of nanosized YVO₄ particles as a novel and efficient nucleating agent on the nonisothermal crystallization behaviors of poly(lactic acid) (PLA) was studied. A modified Avrami model was utilized to describe the nonisothermal crystallization kinetics of pure PLA and PLA nanocomposites. The differential isoconversional Friedmann formula was employed to calculate the effective activation energies (E_X(t) ) of nonisothermal crystallization from the glass state. The results showed that modified Avrami methods describe the nonisothermal crystallization kinetics of pure PLA and PLA nanocomposites well. The crystallization rate of PLA/1 mass% YVO₄ was faster than that of pure PLA sample by factor 5 × 10³ at a heating rate of 1 K min⁻¹. While the values of Lauritzen–Hoffman parameters (K_g and U*) of the PLA/YVO₄ nanocomposites were lower than those of pure PLA, indicating the nucleation efficiency of nanosized YVO₄ particles for PLA. Scanning electron microscopy images reflect the uniform dispersion of 1 mass% YVO₄ in PLA matrix. Thermogravimetric analysis results revealed that the thermal degradation parameters are slightly lowered by 7 °C on increasing the mass percentage of YVO₄ in the PLA nanocomposites. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48340.     

[6]-Gingerol-loaded cellulose acetate electrospun fibers as a topical carrier for controlled release

[6]-Gingerol (6 % w/v)-loaded cellulose acetate (12 % w/v CA; MW ~ 3 × 10⁴ g/mol) fibers (375 ± 107 nm) were prepared by electrospinning at 7.5 kV. ATR-FTIR spectra indicated that the mixture was miscible at this composition. Differential scanning calorimetry revealed that [6]-gingerol was uniformly dispersed in the CA matrix and interrupted the hydrogen bond formation among the CA chains. Controlled release study showed that ~97 % of the loaded [6]-gingerol could be released from the loaded fibers to the acetate buffer solution at 37 °C, whereas only ~74 % of it could be done from the corresponding films. About 92 % of [6]-gingerol in the fibers was dramatically released within 4 h. Release was mainly governed by a diffusion-controlled mechanism. The radical scavenging assay showed antioxidant activity of the loaded fibers. The in vitro cytotoxicity test revealed that the viability of L-929 mouse fibroblast cells to the loaded fibers was ~65 %.     

Evaluation of isophorone diisocyanate crosslinked gelatin as a carrier for controlled delivery of drugs

The high solubility of gelatin in neutral, basic, and acidic biofluids may not promote a controlled drug delivery as a drug carrier. The present study reports the modification of the solubility and swellability of gelatin by crosslinking with hitherto uninvestigated isophorone diisocyanate to achieve controlled drug release characteristics. The crosslinked gelatin was insoluble and swellable in biofluids and analyzed by FT-IR and proton NMR, thermal analysis, swellability and biodegradability in simulated biofluids, X-ray diffraction, biocompatibility, and in vitro drug release kinetics and mechanism with 5-Fluorouracil as model drug. Crosslinking decreased the biodegradability and solubility, and enhanced the amorphous character of gelatin. The mild decrease in thermal stability of crosslinked gelatin was attributed to the urea linkage introduced. Drug release predominately occurred via anomalous transport mechanism with mild degradative diffusion. The observed results demonstrated that crosslinked gelatin can be used as a potential carrier to achieve controlled drug release.     

Hydroxypropylation of cellulose isolated from bamboo (Dendrocalamus strictus) with respect to hydroxypropoxyl content and rheological behavior of the hydroxypropyl cellulose

Bamboo, a lignocellulosic material, is a renewable source of interest as feedstock for production of cellulose derivatives by chemical functionalization. Optimization of hydroxypropylation of cellulosic material (average DP 816), isolated from bamboo (Dendrocalamus strictus) was, therefore, performed with respect to maximum percent hydroxylpropoxyl (% HP) contents under varying reaction conditions and studying their effect on the % HP. The optimized reaction conditions were aqueous NaOH concentration 22%, propylene oxide concentration 17.4 mol/AGU, temperature 50°C, duration of hydroxypropylation 4 h to yield hydroxypropyl cellulose of % HP 65.89. The η_app of 1 and 2% solutions of the optimized product showed it to be non‐Newtonian pseudoplastic. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009