Search Results (139)

In this study, we designed an injectable skin-rejuvenating formulation based on polyethylene glycol–polycaprolactone–polyethylene glycol (PEG-PCL-PEG) copolymers to provide a synergistic combination of biocompatibility, antioxidative capacity, and regenerative potential. Through the systematic optimization of the precursor molar ratio and molecular weight, well-defined PEG-PCL-PEG copolymers were synthesized and structurally characterized using gel permeation chromatography (GPC), proton nuclear magnetic resonance (¹H-NMR), and Fourier transform infrared (FT-IR) spectroscopy. An optimized precipitation and drying protocol effectively reduced residual solvents, as confirmed by gas chromatography (GC). Idebenone was incorporated as an antioxidant to prevent skin aging, while hyaluronic acid (HA), L-arginine, and glycerin were included to promote collagen regeneration. In vitro assays demonstrated that idebenone-loaded samples exhibited prolonged intracellular antioxidant activity with low cytotoxicity. The collagen-promoting formulation, containing HA, glycerin, and L-arginine, enhanced the expression of transforming growth factor-β (TGF-β) and type III collagen (COL3) while suppressing inflammatory genes, suggesting a favorable environment for extracellular matrix remodeling. In vivo evaluation corroborated these outcomes, showing angiogenesis, collagen reorganization, and progressive dermal thickness. Histological analysis further confirmed sustained matrix regeneration and tissue integration. These results highlight the potential of PEG-PCL-PEG-based injectables as a multifunctional platform for collagen regeneration, offering a promising strategy for both cosmetic and clinical applications. Full article

Background: Resorbable biopolymers are increasingly explored for use in regenerative procedures within dental surgery. Their ability to degrade naturally, minimize surgical reinterventions, and potentially reduce immunogenicity makes them appealing in guided bone and tissue regeneration applications. However, despite these advantages, uncertainties persist regarding their comparative effectiveness and associated risks. For example, polyethylene glycol (PEG)-based membranes have shown comparable outcomes to porcine-derived collagen membranes in bone regeneration procedures, yet studies have reported a higher incidence of soft tissue healing complications associated with PEG-based materials. Similarly, while polycaprolactone (PCL) and dextrin-based hydrogels have demonstrated promising clinical handling and bone fill capabilities, their long-term performance and consistency across different anatomical sites remain under investigation. These findings highlight the need for further well-powered clinical trials to establish standardized guidelines for their safe and effective use. Methods: A systematic review protocol was registered with the PROSPERO database and developed in alignment with PRISMA guidelines. Database searches were conducted in PubMed, Medline, Scopus, and Cochrane from June to December 2024. Only randomized controlled trials (RCTs) focusing on synthetic resorbable biopolymers in bone augmentation procedures were considered. Bias was evaluated using the Cochrane Risk of Bias tool. Results: Eleven RCTs were included, totaling 188 patients. The findings suggest that materials such as polylactic acid (PLA), polycaprolactone (PCL), and polyethylene glycol (PEG) contributed effectively to new bone formation. PEG-based membranes were found to perform on par with or occasionally better than traditional collagen membranes derived from porcine sources. Additionally, the application of 3D-printable polymers demonstrated promise in site-specific healing. Conclusions: Resorbable biopolymers are effective and safe for GBR procedures, with clinical outcomes comparable to traditional materials. Advances in 3D-printing technology and bioactive coatings may further enhance their regenerative potential. However, the incidence of soft tissue healing complications suggests the need for further long-term studies to optimize material properties and clinical application. Full article

Background/Objectives: This research focuses on the development and optimization of polymer–lipid hybrid nanoparticles (PLHNs) using two grades of mPEG-PCL co-polymers in combination with DPPC and lecithin to address the biopharmaceutical challenges of acalabrutinib (ACP), a selective treatment for different hematological malignancies. Methods: Variations in the mPEG-to-ε-caprolactone ratio influenced both the molecular weight (Mw) of the synthesized co-polymers and their aqueous phase affinity. The ACP-loaded PLHNs (ACP-PLHNs) were optimized using a circumscribed central composite design. The in vivo studies were performed in Wistar rats. Results: The lipophilic mPEG-PCL (Mw = 9817.67 Da) resulted in PLHNs with a particle size of 155.91 nm and 40.08% drug loading, while the hydrophilic mPEG-PCL (Mw = 23,615.84 Da) yielded PLHNs with a relatively larger size (223.46 nm) and relatively higher drug loading (46.59%). The drug release profiles were polymer-grade dependent: lipophilic ACP-PLHNs (lACP-PLHNs) sustained release up to 30 h in pH 7.2 buffer, while hydrophilic ACP-PLHNs (hACP-PLHNs) completed release within 24 h. Stability studies showed greater stability for lACP-PLHNs, likely due to reduced molecular rearrangement from the chemically stable lipophilic co-polymer. Conclusions: Oral administration of both formulations exhibited a 2-fold (p < 0.001) improvement in the C_max and AUC_0-tlast and a 3.9-fold (p < 0.001) increase in the relatively oral bioavailability compared to the conventional ACP suspension in male wistar rats. Full article

Background and Clinical Significance: To describe the effectiveness of alveolar ridge preservation under the radiological and histological analysis of a customized resorbable scaffold three-dimensionally printed with polycaprolactone (PCL) reinforced with a coating of a copolymer of polycaprolactone-block-polyethylene glycol (PCL–PEG) by electrospray. Case Presentation: A 62-year-old male with vertical root fractures of teeth #14 and #15. From the cone beam CT (CBCT) image, the scaffold root replicas were designed with the shape of the roots and printed with PCL coated with PCL–PEG by electrospray. The scaffold was inserted into the alveolar bone and maintained with a tension-free flap closure. After six months, a CBCT of the surgical site and histological analysis of a bone sample at the dental implant installation site were performed. After 6 months, the wound in tooth #14 was closed, clinically proving no adverse reaction or complications. The histological analysis of the bone sample showed new bone formation with lamellar structure, Haversian canal structure, and osteocyte spaces. However, the scaffold in tooth #15 was exposed and not osseointegrated, and it was covered with membranous tissue. Histologically, the sample showed tissue compatible with lax connective tissue with mixed inflammatory infiltrate. In tooth #14, the dental implant presented an insertion torque >35 Ncm and was rehabilitated three months after its installation. Conclusions: Three-dimensional printed PCL scaffolds showed the ability to regenerate vital and functional bone with osseointegration capability for maxillary bone regeneration and oral rehabilitation based on dental implants. A case of inadequate scaffold osseointegration accompanied by lax connective tissue formation is shown. Full article

Postoperative adhesions (POAs) are a common and often serious complication following abdominal and gynecologic surgeries, leading to infertility, chronic pain, and bowel obstruction. To address these outcomes, the development of anti-adhesion barriers using biocompatible materials has emerged as a key area of biomedical research. This article presents a comprehensive overview of clinically relevant natural and synthetic biomaterials explored for POA prevention, emphasizing their degradation behavior, barrier integrity, and translational progress. Natural biopolymers—such as collagen, gelatin, fibrin, silk fibroin, and decellularized extracellular matrices—are discussed alongside polysaccharides, including alginate, chitosan, and carboxymethyl cellulose, focusing on their structural features and biological functionality. Synthetic polymers, including polycaprolactone (PCL), polyethylene glycol (PEG), and poly(lactic-co-glycolic acid) (PLGA), are also examined for their tunable degradation profiles (spanning days to months), mechanical robustness, and capacity for drug incorporation. Recent innovations, such as bioprinted and electrospun dual-layer membranes, are highlighted for their enhanced anti-fibrotic performance in preclinical studies. By consolidating current material strategies and fabrication techniques, this work aims to support informed material selection while also identifying key knowledge gaps—particularly the limited comparative data on degradation kinetics, inconsistent definitions of ideal mechanical properties, and the need for more research into cell-responsive barrier systems. Full article

Three-dimensional printing, particularly Fused Deposition Modeling (FDM), has revolutionized dermatological drug delivery by offering the ability to create personalized and precise drug formulations. This technology enables the design of customized drug delivery systems using a variety of polymers, such as Polylactic Acid (PLA), Polyvinyl Alcohol (PVA), Polyethylene Glycol (PEG), and Polycaprolactone (PCL), each with unique properties that enhance drug release, patient compliance, and treatment efficacy. This review analyzes these polymers in terms of their advantages, limitations, and suitability for dermatological applications. The ability to tailor these materials offers significant potential in overcoming treatment regimens. Additionally, the customization of three-dimensional-printed drug delivery systems provides a platform for creating patient-specific solutions that are more effective and adaptable to individual needs. Despite challenges such as moisture sensitivity and mechanical brittleness, the potential of FDM technology to improve dermatological treatments remains promising. The future of three-dimensional printing in dermatology lies in the integration of optimized materials and advanced printing techniques, which could further enhance patient-specific care and broaden the clinical applicability of these technologies in the pharmaceutical and biomedical sectors. By addressing these limitations and expanding material choices, FDM-based drug delivery systems have the potential to revolutionize the management of dermatological conditions, offering improved therapeutic outcomes and quality of life for patients. Full article

Background/Objectives: The management of ocular tumours is faced with the challenge of developing a suitable treatment strategy with consideration of the anatomical and physiological protective barriers of the eye. Interferon alpha has been employed to treat patients with ocular tumours for decades; however, its short half-life and poor tolerability necessitate frequent administration. This study focuses on the design of an injectable pH-responsive and protective nanoparticle system dispersed into a thermo-responsive hydrogel for site-specific sustained delivery of interferon alpha (IFN-α2b) in the treatment of ocular surface tumours. Methods: The synthesis of a poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymer (PECE) was undertaken. The IFN-α2b was encapsulated in poly(β-amino ester) (PBAE) nanoparticles (NP) with pH-responsive characteristics to proposedly release the IFNα-2b in response to the acidic nature of the tumour microenvironment. This was followed by characterisation via Fourier transform infrared spectroscopy (FT-IR), ¹H-nuclear magnetic resonance (¹H-NMR) analysis, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) analysis, thermogravimetric analysis (TGA), and thermal-transition analysis of the PECE hydrogels. Results: Release studies demonstrated that the PBAE nanoparticulate PEG-PCL-PEG hydrogel was both pH-responsive, while providing controlled release of IFN-α2b, and thermo-responsive. Release analysis highlighted that IFN-α2b-loaded NP dispersed into the hydrogel (IFNH) further prolonged the release of IFN-α2b with a pH-responsive yet controlled release rate in an acidic environment simulating a tumour microenvironment. The developed system proved to be biocompatible with human retinal pigment epithelial cells and the released IFN-α demonstrated bioactivity in the presence of an A172 glioblastoma cell line. Conclusions: In conclusion, the PECE hydrogel has promising potential for application as an ocular drug delivery system for the treatment of ocular tumours and could potentially overcome and prevent the drawbacks associated with the commercially available IFN-α2b injection. Full article

Recently, various biocompatible and biodegradable materials have garnered significant attention as cosmetic fillers for skin rejuvenation. Among these, poly ε-caprolactone (PCL), poly L-lactic acid (PLLA), poly D,L-lactic acid (PDLLA), and polydioxanone (PDO) microspheres have been developed and commercialized as a dermal filler. However, its irregularly hydrophobic microspheres pose hydration challenges, often causing syringe needle blockages and side effects such as delayed onset nodules and papules after the procedure. In this study, we synthesized a polyethylene glycol-poly D,L-lactic acid (mPEG-PDLLA) copolymer to address the limitations of conventional polymer fillers. Comprehensive characterization of the copolymer was performed using nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The mPEG-PDLLA copolymers demonstrated a unimodal size distribution of approximately 121 ± 20 nm in an aqueous solution. The in vitro cytotoxicity and collagen genesis of mPEG-PDLLA copolymers were evaluated using human dermal fibroblast cells. In this study, angiogenesis was observed over time in hairless mice injected with mPEG-PDLLA copolymers, confirming its potential role in enhancing collagen synthesis. To assess the inflammatory response, the expression levels of the genes MMP1 and IL-1β were analyzed. Additionally, gene expression levels such as transforming growth factor-β and collagen types I and III were compared with Rejuran^® in animal studies. The newly developed collagen-stimulating PEGylated PDLLA may be a safe and effective option for skin rejuvenation. Full article

Hernia repair is the most common surgical operation applied worldwide. Mesh prostheses are used to support weakened or damaged tissue to decrease the risk of hernia recurrence. However, the patches currently used in clinic applications have significant short-term and long-term risks. This study aimed to design, produce, and characterize a three-layered semi-resorbable composite hernia mesh using the electrospinning technique, where the upper layer (parietal side) was made of non-resorbable polypropylene (PP-Cl) fibers, the partially resorbable middle layer was made of PP-Cl and polycaprolactone (PCL) fibers, and the fully resorbable lower layer (visceral side) was made of H. perforatum oil-loaded polyethylene glycol (PEG) fibers. The extracellular matrix-like fibrous structure of the patches provided low density and high porosity, minimizing the risk of long-term foreign body reactions, and the hydrophilic/hydrophobic character of the surfaces and the detected swelling rates supported biocompatibility. The patches exhibited mechanical properties comparable to commercially available products. Controlled release of therapeutic oil could be achieved from the oil-integrated patches due to the dissolution of PEG in the acute process. In vitro cell culture studies with the L929 mouse fibroblast cell line revealed that the meshes do not have a cytotoxic nor a biomaterial-induced necrotic effect that will induce apoptosis of the cells. The visceral side of the meshes exhibited non-adherence of cell-like structures to the surface due to the dissolution of PEG. The composite hernia patches were concluded to reduce the risk of adhering to internal organs in the hernia area, have the potential to be used in in vivo biomedical applications, and will support the search for an ideal hernia mesh that can be used in the treatment of abdominal hernias. Full article

Background/Objectives: We previously demonstrated that the intranasal administration of cell-penetrating Tat peptide-modified carrier, PEG-PCL-Tat, improves drug delivery to the central nervous system. This study aimed to evaluate the potential of the post-onset intranasal administration of N-acetyl-L-cysteine (NAC) combined with PEG-PCL-Tat (NAC/PPT) for neuropathic pain. Methods: Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) in mice. Mechanical allodynia was assessed using the von Frey test on days 11–14 post-ligation. NAC or NAC/PPT was intranasally administered after pain onset. Western blotting and immunohistochemistry were conducted to evaluate ionized calcium-binding adapter molecule 1 (Iba-1) expression and microglial activation in the spinal cord. Results: Mechanical allodynia was exacerbated 11 days after the ligation in PSNL mice. The intranasal administration of NAC alone prevented allodynia exacerbation but failed to provide a therapeutic effect against allodynia in PSNL mice. In contrast, NAC/PPT administration ameliorated PSNL-induced tactile allodynia, with maximum efficacy seen 13 and 14 days after ligation. Western blotting demonstrated that Iba-1 levels tended to increase in PSNL mice compared to controls. This trend of increased Iba-1 levels in PSNL mice was attenuated by the administration of NAC/PPT, but not by NAC alone. Immunohistochemistry revealed an increased number of Iba-1-stained microglia in the ipsilateral spinal cord of PSNL mice, which were significantly suppressed by the administration of NAC/PPT. Conclusions: These results suggest that the post-onset intranasal administration of NAC/PPT ameliorates mechanical allodynia by suppressing microglia induction and that intranasal delivery with PEG-PCL-Tat might be a useful tool for the pharmacological management of neuropathic pain. Full article

Impaired contractility after myocardial infarction (MI) causes cardiogenic shock. MARK4 activity impairs contractility post-MI by increasing α-tubulin detyrosination. We assessed the impact of naringenin, a small-molecule MARK4 inhibitor, on contractility post-MI. Naringenin (Nar) was encapsulated in PEG-PCL to augment bioavailability. Wistar rats were randomized to receive either MI + micellized naringenin (0.3 mg/kg) [MI-NarMic], MI + naringenin (0.3 mg/kg) in 1% DMSO [MI-NarDMSO], MI + empty micelle [MI-Mic], MI alone [MI-Untreated], or no MI [Sham]. MI was induced via left anterior descending artery ligation. Invasive hemodynamics with pressure–volume catheterization, cardiomyocyte contractility, and ventricular protein abundance were assessed one day post-MI. A total of 45 rats underwent hemodynamic assessment. MI-NarMic rats demonstrated decreased α-tubulin detyrosination relative to MI-Untreated rats (p < 0.05). Myocytes isolated from peri-infarct tissue had increased contraction and relaxation velocities in MI-NarMic versus MI-Untreated rats (both p < 0.0001). MI-NarMic rats had higher ejection fractions than MI-Mic and MI-Untreated rats (63 ± 3% v. 48 ± 5% vs. 39 ± 4%, p < 0.05) and similar levels to Sham (61 ± 1%, p = 0.97) and MI-NarDMSO (54 ± 5%) rats (p > 0.05). MI-Nar rats had greater stroke work and lower end-diastolic pressure and tau than MI-Untreated rats (all p < 0.05). Micellized naringenin is a translatable agent with the potential to rescue hemodynamics post-MI by inhibiting MARK4 and mitigating myocardial α-tubulin detyrosination. Full article

The efficiency of drug delivery from coatings of metallic implants is one of the key factors. The influence of chemical and thermal treatments of nitinol wire on the corrosion properties, deposition of hydroxyapatite(HA)/poly ε-caprolactone-polyethylene glycol (PEG-b-PCL), and the amount of ibuprofen released from that bilayer were studied. The hydroxyapatite layer was electrodeposited by pulse current, while the PEG-b-PCL layer was by drop-coating. It was shown that nitinol wire, chemically treated and thermally heated at 470 °C under optimized conditions, is the most optimal substrate for the deposition of uniform and compact hybrid HA/(PEG-b-PCL) bilayer. Ibuprofen incorporated into this hybrid bilayer exhibits the maximum release into phosphate-buffered saline (PBS) solution. About 80% of ibuprofen is released within 5 h. Full article

Nanocomposites prepared with a terpolymer of poly(L–lactide) (PLLA)–poly(ε–caprolactone) (PCL)–poly(ethylene glycol) (PEG) and partially oxidized carbon nanotubes (CNTs_po) were synthesized and characterized to evaluate their ability to act as an effective nanocarrier of the anticancer drug methotrexate. The homopolymers of PLLA and PCL were synthesized through ring-opening polymerization (ROP) and characterized through gel permeation chromatography (GPC). The PLLA–PCL–PEG terpolymers were synthesized through a four-step chemical route using oxalyl chloride as a linker agent and analyzed with ¹H–NMR, ¹³C–NMR, and FTIR spectroscopies. Additionally, the nanocomposites were characterized through FTIR, and X-ray photoelectron spectroscopy (XPS), as well as the differential scanning calorimetry (DSC) technique. XPS analysis revealed that PLLA–PCL–PEG terpolymer chains are grafted onto CNTs_po. Moreover, evaluations through FTIR and DSC strongly suggest that the PCL-rich domains are preferentially oriented toward CNTs_po. The release tests exhibited a “burst effect” profile, which was more evident in the terpolymers than in the nanocomposites. Five models were used to assess methotrexate’s in vitro release. For the nanocomposites, the best fit to the experimental data was obtained using the first-order model, whereas the results obtained from the Korsmeyer–Peppas model indicated that Fickian diffusion drives methotrexate’s release. Full article

Needle-free buccal anesthesia improves dental treatment outcomes for both patients and dentists. In this study, we report on an assessment of the enhancement effects of α-bisabolol on the in vitro transmucosal permeation of prilocaine hydrochloride (PCl) and lidocaine hydrochloride (LCl) from needleless buccal films. We also evaluated the mechanical properties of the film, which consisted of Methocel™ K100 LV as the film-forming polymer (3% m·m⁻¹), PEG 400 as a cosolvent (15% m·m⁻¹ based on drug loading), α-bisabolol (15 and 30% m·m⁻¹ based on drug loading), and the drugs combined at a 1:1 ratio (15 mg·unit⁻¹). The porcine esophageal epithelium was used as a membrane barrier, and artificial saliva was the release medium. After a 1 h experiment at 25 ± 2 °C, α-bisabolol significantly decreased, rather than enhanced, the permeation fluxes (five-fold), permeability coefficients (seven-fold), and retentions (two-fold) of both PCl and LCl through the epithelium, regardless of the concentration. Moreover, the resistance and flexibility of the films markedly decreased compared to those without α-bisabolol. Therefore, under the experimental conditions, using α-bisabolol as a buccal permeation enhancer for the hydrophilic local anesthetics PCl and LCl from buccal films is not feasible. Full article

In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the oxalate transferrin variant (oxalate Tf) and incorporated into three-dimensional chitosan hydrogels. This innovative approach represents the first application of oxalate Tf for the precision delivery of drug-loaded polymersomes within a semi-solid dosage form based on chitosan hydrogels. These resulting semi-solids exhibited a sustained release profile for both encapsulated drugs. To evaluate their potency, we compared the cytotoxicity of native Tf-Ps with oxalate Tf-Ps. Notably, the oxalate Tf-Ps demonstrated a 3-fold decrease in cell viability against melanoma cells compared to normal cells and were 1.6-fold more potent than native Tf-Ps, indicating the greater potency of this nanoformulation. These findings suggest that dual-drug delivery using an oxalate-Tf-targeting ligand significantly enhances the drug delivery efficiency of Tf-conjugated nanovesicles and offers a promising strategy to overcome the challenge of multidrug resistance in melanoma therapy. Full article