Search Results (7)

The present study investigates the utilization of nanoparticles based on poly-l-lactide (PLLA) and polyglycerol adipate (PGA), alone and blended, for the encapsulation of usnic acid (UA), a potent natural compound with various therapeutic properties including antimicrobial and anticancer activities. The development of these carriers offers an innovative approach to overcome the challenges associated with usnic acid’s limited aqueous solubility, bioavailability, and hepatotoxicity. The nanosystems were characterized according to their physicochemical properties (among others, size, zeta potential, thermal properties), apparent aqueous solubility, and in vitro cytotoxicity. Interestingly, the nanocarrier obtained with the PLLA-PGA 50/50 weight ratio blend showed both the lowest size and the highest UA apparent solubility as well as the ability to decrease UA cytotoxicity towards human hepatocytes (HepG2 cells). This research opens new avenues for the effective utilization of these highly degradable and biocompatible PLLA-PGA blends as nanocarriers for reducing the cytotoxicity of usnic acid. Full article

This study aimed to fabricate new variations of glycerol-based polyesters by grafting poly(glycerol adipate) (PGA) with hydrophobic bioactive moieties, tocopherol (TOC), and cholesterol (CHO). Their effects on nanoparticle (NP) formation, drug release, and cellular responses in cancer and normal cells were evaluated. CHO and TOC were successfully grafted onto PGA backbones with 30% and 50% mole grafting. Increasing the percentage of mole grafting in both molecules increased the glass transition temperature and water contact angle of the final polymers but decreased the critical micelle concentration of the formulated particles. PGA-TOC NPs reduced the proliferation of MDA-MB-231 cancer cells. However, they enhanced the proliferation of primary dermal fibroblasts within a specific concentration range. PGA-CHO NPs minimally affected the growth of cancer and normal cells. Both types of NPs did not affect apoptosis or the cell cycle of cancer cells. PGA-CHO and PGA-TOC NPs were able to entrap SN-38, a hydrophobic anticancer drug, with a particle size <200 nm. PGA-CHO NPs had a higher drug loading capacity and a greater drug release than PGA-TOC NPs. However, SN-38-loaded PGA-TOC NPs showed higher toxicity than SN-38 and SN-38-loaded PGA-CHO NPs due to the combined effects of antiproliferation and higher cellular uptake. Compared with SN-38, the drug-loaded NPs more profoundly induced sub-G1 in the cell cycle analysis and apoptosis of cancer cells in a similar pattern. Therefore, PGA-CHO and PGA-TOC polymers have potential applications as delivery systems for anticancer drugs. Full article

Enzymatic one-pot synthesis procedures in a one-step and two-step monomers addition were developed to obtain poly(glycerol adipate) macromers with methacrylate end-functional groups under the presence of 1 and 3 wt% of Candida antarctica lipase B (CALB). Glycerol, divinyl adipate, and vinyl methacrylate were enzymatically reacted (vinyl methacrylate was either present from the beginning in the monomers solution or slowly dropped after 6 h of reaction) in tetrahydrofuran (THF) at 40 °C over 48 h. Macromers with a methacrylate end groups fraction of ≈52% in a simple one-pot one-step procedure were obtained with molecular weights (M_n) of ≈7500–7900 g/mol. The obtained products under the one-pot one-step and two steps synthesis procedures carried out using 1 and 3 wt% of a CALB enzymatic catalyst were profusely characterized by NMR (¹H and ¹³C), MALDI-TOF MS, and SEC. The methacrylate functional macromers obtained with the different procedures and 1 wt% of CALB were combined with an Irgacure^® 369 initiator to undergo homopolymerization under UV irradiation for 10 and 30 min, in order to test their potential to obtain amorphous networks within minutes with similar properties to those typically obtained by complex acrylation/methacrylation procedures, which need multiple purification steps and harsh reagents such as acyl chlorides. To the best of our knowledge, this is the first time that it has been demonstrated that the obtention of methacrylate-functional predominantly linear macromers based on poly(glycerol adipate) is able to be UV crosslinked in a simple one-step procedure. Full article

This study aimed to improve the anticancer effect of Cordyceps militaris herbal extract (CME) on breast cancer cells with hyaluronic acid (HYA) surface-decorated lipid polymer hybrid nanoparticles (LPNPs) and evaluate the applicability of a synthesized poly(glycerol adipate) (PGA) polymer for LPNP preparation. Firstly, cholesterol- and vitamin E-grafted PGA polymers (PGA-CH and PGA-VE, respectively) were fabricated, with and without maleimide-ended polyethylene glycol. Subsequently, CME, which contained an active cordycepin equaling 9.89% of its weight, was encapsulated in the LPNPs. The results revealed that the synthesized polymers could be used to prepare CME-loaded LPNPs. The LPNP formulations containing Mal-PEG were decorated with cysteine-grafted HYA via thiol-maleimide reactions. The HYA-decorated PGA-based LPNPs substantially enhanced the anticancer effect of CME against MDA-MB-231 and MCF-7 breast cancer cells by enhancing cellular uptake through CD44 receptor-mediated endocytosis. This study demonstrated the successful targeted delivery of CME to the CD44 receptors of tumor cells by HYA-conjugated PGA-based LPNPs and the new application of synthesized PGA-CH- and PGA-VE-based polymers in LPNP preparation. The developed LPNPs showed promising potential for the targeted delivery of herbal extracts for cancer treatment and clear potential for translation in in vivo experiments. Full article

Nanoparticle (NP) drug delivery systems are known to potentially enhance the efficacy of therapeutic agents. As for antimicrobial drugs, therapeutic solutions against drug-resistant microbes are urgently needed due to the worldwide antimicrobial resistance issue. Usnic acid is a widely investigated antimicrobial agent suffering from poor water solubility. In this study, polymer nanoparticles based on polyglycerol adipate (PGA) grafted with polycaprolactone (PCL) were developed as carriers for usnic acid. We demonstrated the potential of the developed systems in ensuring prolonged bactericidal activity against a model bacterial species, Staphylococcus epidermidis. The macromolecular architecture changes produced by PCL grafted from PGA significantly influenced the drug release profile and mechanism. Specifically, by varying the length of PCL arms linked to the PGA backbone, it was possible to tune the drug release from a burst anomalous drug release (high PCL chain length) to a slow diffusion-controlled release (low PCL chain length). The developed nanosystems showed a prolonged antimicrobial activity (up to at least 7 days) which could be used in preventing/treating infections occurring at different body sites, including medical device-related infection and mucosal/skin surface, where Gram-positive bacteria are commonly involved. Full article

The enzymatically synthesized poly (glycerol adipate) (PGA) has demonstrated all the desirable key properties required from a performing biomaterial to be considered a versatile “polymeric-tool” in the broad field of drug delivery. The step-growth polymerization pathway catalyzed by lipase generates a highly functionalizable platform while avoiding tedious steps of protection and deprotection. Synthesis requires only minor purification steps and uses cheap and readily available reagents. The final polymeric material is biodegradable, biocompatible and intrinsically amphiphilic, with a good propensity to self-assemble into nanoparticles (NPs). The free hydroxyl group lends itself to a variety of chemical derivatizations via simple reaction pathways which alter its physico-chemical properties with a possibility to generate an endless number of possible active macromolecules. The present work aims to summarize the available literature about PGA synthesis, architecture alterations, chemical modifications and its application in drug and gene delivery as a versatile carrier. Following on from this, the evolution of the concept of enzymatically-degradable PGA-drug conjugation has been explored, reporting recent examples in the literature. Full article

Starch is one of the most abundant polysaccharides on the earth and it is the most important source of energy intake for humans. Thermoplastic starch (TPS) is also widely used for new bio-based materials. The blending of starch with other molecules may lead to new interesting biodegradable scaffolds to be exploited in food, medical, and pharmaceutical fields. In this work, we used native starch films as biopolymeric matrix carriers of chemo enzymatically-synthesized poly (glycerol-adipate) (PGA) nanoparticles (NPs) to produce a novel and biocompatible material. The prototype films had a crystallinity ranging from 4% to 7%. The intrinsic and thermo-mechanical properties of the composite showed that the incorporation of NPs in the starch films decreases the glass transition temperature. The utilization of these film prototypes as the basis for new biocompatible material showed promise, particularly because they have a very low or even zero cytotoxicity. Coumarin was used to monitor the distribution of the PGA NPs in the films and demonstrated a possible interaction between the two polymers. These novel hybrid nanocomposite films show great promise and could be used in the future as biodegradable and biocompatible platforms for the controlled release of amphiphilic and hydrophobic active ingredients. Full article