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
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