The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs, and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs. Recently, certain drugs have been found to form crystalline inclusion complexes (ICs) with multiple types of linear polymers, representing a new subcategory of pharmaceutical solids. In this study, we used diflunisal (DIF) as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL). The block length in the guest copolymers showed a significant influence on the formation, thermal stability and dissolution behavior of the DIF ICs. Though the PEG block could hardly be included alone, it could indeed be included in the DIF ICs when the PCL block was long enough. The increase of the PCL block length produced IC crystals with improved thermal stability. The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length. These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner. 相似文献
Poly(ethylene glycol) (PEG) is widely used as a water soluble carrier for polymer-drug conjugates. Herein, we report degradable linear PEG analogs (DPEGs) carrying multifunctional groups. The DPEGs were synthesized by a Michael addition based condensation polymerization of dithiols and PEG diacrylates (PEGDA) or dimethacrylates (PEGDMA). They were stable at pH 7.4 but quickly degraded at pH 6.0 and 5.0. Thus, DPEGs could be used as drug carriers without concern for their retention in the body. DPEGs could be made to carry such functional groups as terminal thiol or (meth)acrylate and pendant hydroxyl groups. The functional groups were used for conjugation of drugs and targeting groups. This new type of PEG analog will be useful for drug delivery and the PEGylation of biomolecules and colloidal particles. 相似文献
Finasteride is a practically insoluble in water drug that belongs to the Class II of the BCS (poor solubility and high permeability). Solid dispersions are solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. Solid dispersions are a successful strategy to improve drug release of poorly water-soluble drugs such as finasteride. Natural cyclodextrins are doughnut-shaped molecules with an internal hydrophobic cavity and a hydrophilic external surface. The lipophilic cavity enables cyclodextrins to form non-covalent inclusion complexes with a wide variety of poorly water-soluble drugs such as finasteride. The aim of this study was to investigate the formation of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions and finasteride:??-cyclodextrin inclusion complexes by solvent evaporation method using a mixture of water:ethanol (1:1). The formation of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions and finasteride:??-cyclodextrin inclusion complexes was investigated and characterized by differential scanning calorimetry (DSC), infrared (IR) spectroscopy, and dissolution studies from capsules containing a quantity equivalent to 5 mg of finasteride. The DSC thermograms revealed the transformation of finasteride into the amorphous state in solid dispersions with PEG 6000 and Kollidon K25, and in inclusion complexes with ??-cyclodextrin. The IR spectra demonstrated molecular interaction in solid dispersions of finasteride with PEG 6000, and in inclusion complexes with ??-cyclodextrin. Dissolution rate of solid dispersions and inclusion complexes was significantly greater than that of corresponding physical mixtures and pure drug, indicating that the formation of solid dispersions and inclusion complexes increased the solubility of the poorly soluble drug, finasteride. 相似文献
The development of thermo‐responsive and reduction‐sensitive polymeric micelles based on an amphiphilic block copolymer poly[(PEG‐MEMA)‐co‐(Boc‐Cyst‐MMAm)]‐block‐PEG (denoted PEG‐P‐SS‐HP) for the intracellular delivery of anticancer drugs is reported. PTX, as model drug, was loaded into the PEG‐P‐SS‐HP micelles with an encapsulation efficiency >90%, resulting in a high drug loading content (up to 35 wt%). The PTX‐loaded PEG‐P‐SS‐HP micelles show slow drug release in PBS and rapid release after incubation with DTT. The PTX‐loaded micelles display a better cytotoxic effect than the free drug, whereas empty micelles are found to be non‐toxic. The thermo‐responsive and reduction‐sensitive polymeric micelles described may serve as promising carriers for cytostatic drugs.
Light scattering has proved to be useful in characterizing colloidal systems. We have studied the interaction between an amphiphilic drug, amitriptyline hydrochloride (AMT), and neutral polymers, polyvinylpyrrolidone (PVP) and poly(ethylene glycol) (PEG), using the dynamic light scattering (DLS) technique. AMT was found to interact with PVP more strongly than PEG. A large decrease of the size of aggregates upon increase of AMT concentration indicates a successive collapse of the polymer conformation. The partial negatively charged oxygen atoms, present in the amide group of PVP, were believed to be responsible for the collapse while interacting with the cationic head group of AMT. Presence of NaBr in the solution enhanced the effect markedly and made the AMT–PVP aggregates more compact. The PEG aggregates also showed a similar behavior, although less pronounced than the PVP. The results obtained in the present investigations may be helpful to design the drug delivery systems for the antidepressant drugs as the higher concentration of these drugs is harmful for the human body. Likewise, as the results have shown that on increasing the temperature there is a decrease in the extent of interaction; this may be helpful for the controlled release formulations. 相似文献
Nanocarriers play an important role in drug delivery for disease treatment. However, nanocarriers face a series of physiological barriers after administration such as blood clearance, nonspecific tissue/cell localization, poor cellular uptake, and endosome trapping. These physiological barriers seriously reduce the accumulation of drugs in target action site, which results in poor therapeutic efficiency. Although polyethylene glycol (PEG) can increase the blood circulation time of nanocarriers, its application is limited due to the “PEG dilemma”. Zwitterionic polymers have been emerging as an appealing alternative to PEG owing to their excellent performance in resisting nonspecific protein adsorption. Importantly, the diverse structures bring functional versatility to zwitterionic polymers beyond nonfouling. This review focuses on the structures and characters of zwitterionic polymers, and will discuss and summarize the application of zwitterionic polymers for drug delivery. We will highlight the strategies of zwitterionic polymers to address the physiological barriers during drug delivery. Finally, we will give some suggestions that can be utilized for the development of zwitterionic polymers for drug delivery. This review will also provide an outlook for this field. Our aim is to provide a comprehensive and systemic review on the application of zwitterionic polymers for drug delivery and promote the development of zwitterionic polymers. 相似文献
Purposes of this paper were to prepare and study
new drug delivery systems for both flavanone glycosides and their aglycones
based on solid-dispersion systems. These compounds are poor water soluble
drugs, so an enhancement of their dissolution is a high priority. Solid-dispersion
systems were prepared using PVP, PEG and mannitol as drug carrier matrices.
Characterizations of these dispersions were done by differential scanning
calorimeter (DSC) and X-ray diffraction (XRD). The glass transition (Tg) temperature of PVP was
only recorded in the DSC thermograms of PVP solid-dispersions of both flavanone
glycosides and their aglycones, while in case of PEG and mannitol solid-dispersions
endotherms of both glycosides and aglycones were noticed with low peak intensity,
indicating that high percent of drug is in amorphous state. The XRD patterns
of all PVP solid-dispersions of aglycones show typical amorphous materials,
but XRD patterns of their glycosides reveal the presence of crystalline material.
However, in all solid dispersions shifts in Tg
of PVP as well as Tm
of PEG were observed, indicating the existence of some interactions between
drugs and matrices. SEM and TEM microscopy revealed that PVP/aglycone flavanone
compounds are nanodispersed systems while all the other solid dispersions
are microcrystalline dispersions. The solubility of both flavanone glycosides
and their aglycones was directly affected by the new physical state of solid
dispersions. Due to the amorphous drug state or nano-dispersions in PVP matrices,
the solubility was enhanced and found to be 100% at pH 6.8 in the nano-dispersion
containing 20 mass% of aglycones. Also solubility enhancement was occurred
in solid dispersions of PEG and mannitol, but it was lower than that of PVP
nano-dispersions due to the presence of the drug compounds in crystalline
state in both matrices. 相似文献
A series of poly(?‐caprolactone/glycolide)‐poly(ethylene glycol) (P(CL/GA)‐PEG) diblock copolymers were prepared by ring opening polymerization of a mixture of ?‐caprolactone and glycolide using mPEG as macro‐initiator and stannous octoate as catalyst. Self‐assembled micelles were prepared from the copolymers using nanoprecipitation method. The micelles were spherical in shape. The micelle size was larger for copolymers with longer PEG blocks. In contrast, the critical micelle concentration of copolymers increased with decreasing the overall hydrophobic block length. Drug loading and drug release studies were performed under in vitro conditions, using paclitaxel as a hydrophobic model drug. Higher drug loading was obtained for micelles with longer poly(ε‐caprolactone) blocks. Faster drug release was obtained for micelles of mPEG2000 initiated copolymers than those of mPEG5000 initiated ones. Higher GA content in the copolymers led to faster drug release. Moreover, drug release rate was enhanced in the presence of lipase from Pseudomonas sp., indicating that drug release is facilitated by copolymer degradation. The biocompatibility of copolymers was evaluated from hemolysis, dynamic clotting time, and plasma recalcification time tests, as well as MTT assay and agar diffusion test. Data showed that copolymer micelles present outstanding hemocompatibility and cytocompatibility, thus suggesting that P(CL/GA)‐PEG micelles are promising for prolonged release of hydrophobic drugs. 相似文献
Summary: Biodegradable amphiphilic poly(ether-anhydride) gel nanoparticles (GNPs) with a hydrophobic crosslinked core and a hydrophilic PEG shell have been prepared from amphiphilic photo-crosslinkable ether-anhydride macromers via microemulsion photo-polymerization. The properties of the GNPs, such as degradability, size and drug-loading capacity, were investigated by tailoring the length of PEG chains in macromers from 400 to 4000 and by the addition of a hydrophobic photo-crosslinkable monomer: stearic monoacrylic anhydride (MSA). TEM showed that the GNPs were spherical in shape with a core-shell structure when MSA was added. The GNPs were used as the carriers to enhance the solubility of hydrophobic drugs. Indomethacin (IND) as a model drug was entrapped in the hydrophobic crosslinked core by an in situ embedding method. Results showed that IND maintained chemically intact during the formulation process, and its dissolution rate were improved compared to those of the pure IND. The GNPs prepared from PEG macromer (molecular weight: 4000) with the addition of MSA exhibited the zero-order release behavior, which is potentially useful to control the release of hydrophobic drugs. 相似文献
