Current Issue : January-March Volume : 2023 Issue Number : 1 Articles : 5 Articles
Biodegradable polymers contain chains that are hydrolytically or enzymatically cleaved, resulting in soluble degradation products. Biodegradability is particularly desired in biomedical applications, in which degradation of the polymer ensures clearance from the body and eliminates the need for retrieval or explant. In this study, a homologues series of poly(ε-caprolactone)-bpoly( ethylene adipate)-b-poly(ε-caprolactone) (PCL-b-PEA-b-PCL) block copolymers, with constant PEA molar mass and different PCL sequence lengths was obtained. The starting point of these copolymers was a dihydroxy-PEA precursor with a molar mass (Mn) of 2500 g/mol. Mn values of the PCL varied between 1000 and 10,000 g/mol. Both the precursors and the copolymers were characterized using different physicochemical methods, such as: NMR, SEC, Maldi-TOFF, DSC, and ATG. The molecular characteristics of the copolymers were in a direct correlation with the sequence length of the PCL. Enzymatic degradability studies were also conducted by using cell-free extract containing Pseudomonas aeruginosa PAO1 for 10 and 21 days, and it appeared that the presence of the PEA central sequence has an important influence on the biodegradability of the copolymer samples. In fact, copolymer PCL7000-PEA2500-PCL7000 had a weight loss of around 50% after 10 days whereas the weight loss of the homopolymer PCL, with a similar Mn of 14,000 g/mol, was only 6%. The results obtained in this study indicate that these copolymer samples can be further used for the preparation of drug delivery systems with modulated biodegradability....
There is an unmet need for novel therapeutic tools relieving chronic pain. Hydrogen sulfide (H2S) is highly involved in pain processes; however, the development of ideal matrices for sulfide donor compounds remains a great pharmaceutical challenge. We aimed to establish a suitable transdermal therapeutic system (TTS) using the H2S donor diallyl disulfide (DADS) as a model compound. After the preparation of DADS, its solubility was investigated in different liquid excipients (propylene glycol, polyethylene glycol, silicone oil) and its membrane diffusivity was assessed in silicone matrices of different compositions. Drug-releasing properties of DADS-containing patches with different silicone oil contents were determined with Franz and flow-through cells. We found a correlation between the liquid excipient content of the patch and the diffusion rate of DADS. DADS showed the best solubility in dimethyl silicone oil, and the diffusion constant was proportional to the amount of oil above the 3 m/m% threshold value. The 8-day-old patch showed a significantly lower, but better-regulated, drug release over time than the 4-day-old one. In conclusion, the siliconebased polymer matrix developed in this study is suitable for stable storage and optimal release of DADS, providing a good basis for a TTS applied in chronic pain....
Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. The MET–CNW–ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 μm and a ζ-potential of −43 mV. In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. The introduction of CNWs into the MET–ALG system not only prolonged the drug release, but also increased the mucoadhesive properties by about 1.3 times. Thus, novel CNW–ALG hydrogels are promising carriers for pH sensitive drug delivery carriers....
Polymeric micelle forming from self-assembly of amphiphilic macromolecules is one of the most potent drug delivery systems. Fatty acids, naturally occurring hydrophobic lipid components, can be considered as potential candidates for the fabrication of block copolymer micelles. However, examples of synthesis of responsive block copolymers using renewable fatty acids are scarce. Herein, we report the synthesis, characterization and testing of block copolymer micelles composed of a renewable fatty-acid-based hydrophobic block and thermoresponsive hydrophilic block for controlled drug delivery. The block copolymers of functionalized fatty acid and poly(N-isopropylacrylamide) (PNIPAM) were prepared via consecutive microwave-assisted reversible addition fragmentation chain transfer (RAFT) polymerization. The block copolymers with variable hydrophobic block length self-assembled in aqueous media and formed spherical nanoparticles of ~30nm with low critical micelle concentration (CMC). To demonstrate the proof-of-concept, carbamazepine (CBZ) was used as a hydrophobic model drug to evaluate the performance of these micelles as nanocarriers. The in vitro drug release tests were carried out below (25 ◦C) and above (37 ◦C) the lower critical solution temperature (LCST) of the block copolymer. The drug release showed obvious temperature-triggered response and an accelerated drug release at 37 ◦C....
Thiolated cyclodextrins are structurally simple mucoadhesive macromolecules, which are able to host drugs and increase their apparent water solubility, as well as interact with the mucus layer prolonging drug residence time on the site of absorption. The aim of this study was to synthesize through green microwave-assisted process a freely soluble thiolated 2-methyl-β-cyclodextrin (MβCDSH). Its inclusion complex properties with dexamethasone (Dex), a poor water soluble drug, and mucoadhesive characteristics were also determined. The product was deeply characterized through NMR spectroscopy (2D COSY, 2D HSQC, 1D/2D TOCSY, and 1D ROESY), showing a thiolation degree of 67%, a selective thiolation on the C6 residues and a monomeric structure. The association constant of MβCD and MβCD-SH with Dex resulted in 2514.3 ± 32.3 M−1 and 2147.0 ± 69.3 M−1, respectively, indicating that both CDs were able to host the drug. Microrheological analysis of mucin in the presence of MBCD-SH showed an increase of complex viscosity, G' and G”, due to disulphide bond formation. The cytotoxicity screening on fibroblast BALB/3T3 clone A31 cells indicated an IC50 of 27.7 mg/mL and 30.0 mg/mL, for MβCD and MβCD-SH, respectively. Finally, MβCD-SH was able to self-assemble in water into nanometric structures, both in the presence and absence of the complexed drug....
Loading....