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1.
J Mater Chem B ; 9(29): 5861-5868, 2021 07 28.
Article in English | MEDLINE | ID: mdl-34259271

ABSTRACT

The deformation shrinkage of a poly(lactide-co-glycolide) (PLGA) fibrous material seriously affects its biomedical application. To demonstrate the underlying shrinking mechanism and to find a method to prevent the shrinkage of an electrospun PLGA membrane, we investigated the shrinking behavior of PLGA electrospun membranes under various test conditions and discussed the underlying shrinking mechanism. The results indicated that the shrinkage of the electrospun PLGA membrane was mainly regulated by the glass transition of its polymer fiber; the temperature and liquid environment were found to be the two main factors leading to the shrinkage of the electrospun PLGA membrane through affecting its glass transition. Then a heat stretching (HS) technique was proposed by us to stabilize the electrospun PLGA membrane. After HS treatment, the glass transition temperature (Tg) of the electrospun PLGA membrane could increase from 48.38 °C to 54.55 °C. Our results indicated that the HS-treated membranes could maintain a high area percentage of 90.89 ± 2.27% and 84.78 ± 3.36% after immersion respectively in PBS and blood at 37 °C for 2 hours. Further experiments confirmed that the HS technique could also stabilize the dimensional structure of the electrospun PDLLA membrane in PBS and blood at 37 °C. This study provides an effective strategy for preventing the shrinkage of electrospun polyester biomaterials in a physiological environment that may benefit both the material structural stability and the in vivo biological performance.


Subject(s)
Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Animals , Dimethylformamide/chemistry , Glass/chemistry , Methylene Chloride/blood , Methylene Chloride/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/blood , Rats , Temperature , Tensile Strength
2.
Nanomedicine ; 30: 102291, 2020 11.
Article in English | MEDLINE | ID: mdl-32841737

ABSTRACT

Polylactide-co-glycolide (PLGA) nanoparticles are one of the most commonly explored biodegradable polymeric drug carriers for inhaled delivery. Despite their advantages as inhalable nanomedicine scaffolds, we still lack a complete understanding of the kinetics and major pathways by which these materials are cleared from the lungs. This information is important to evaluate their safety over prolonged use and enable successful clinical translation. This study aimed to determine how the size and charge of 3H-labeled PLGA nanoparticles affect the kinetics and mechanisms by which they are cleared from the lungs and their safety in the lungs. The results showed that lung clearance kinetics and retention patterns were more significantly defined by particle size, whereas lung clearance pathways were largely influenced by particle charge. Each of the nanoparticles caused transient inflammatory changes in the lungs after a single dose that reflected lung retention times.


Subject(s)
Lung/metabolism , Nanoparticles/administration & dosage , Polylactic Acid-Polyglycolic Acid Copolymer/administration & dosage , Animals , Bronchoalveolar Lavage Fluid , Drug Administration Routes , Lung/immunology , Male , Nanoparticles/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/blood , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/pharmacokinetics , Rats , Rats, Sprague-Dawley , Tissue Distribution , Trachea
3.
Colloids Surf B Biointerfaces ; 188: 110816, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31991290

ABSTRACT

Nanoparticles (NPs) based on biocompatible and biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) represent effective systems for systemic drug delivery. Upon injection into the blood circuit, the NP surface is rapidly modified due to adsorption of proteins that form a 'protein corona' (PC). The PC plays an important role in cellular targeting, uptake and NP bio-distribution. Hence, the study of interactions between NPs and serum proteins appears as key for biomedical applications and safety of NPs. In the present work, we report on the comparative protein fluorescence quenching extent, thermodynamics of protein binding and identification of proteins in the soft and hard corona layers of PLGA and PCL NPs. NPs were prepared via a single emulsion-solvent evaporation technique and characterized with respect to size, zeta potential, surface morphology and hydrophobicity. Protein fluorescence quenching experiments were performed against human serum albumin. The thermodynamics of serum protein binding onto the NPs was studied using isothermal titration calorimetry. Semi-quantitative analysis of proteins in the PC layers was conducted using gel electrophoresis and mass spectrometry using human serum. Our results demonstrated the influence of particle hydrophobicity on the thermodynamics of protein binding. Human serum proteins bind to a greater extent and with greater affinity to PCL NPs than PLGA NPs. Several proteins were detected in the hard and soft corona of the NPs, representing their unique proteome fingerprints. Some proteins were unique to the PCL NPs. We anticipate that our findings will assist with rational design of polymeric NPs for effective drug delivery applications.


Subject(s)
Nanoparticles/chemistry , Polyesters/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Serum Albumin, Human/chemistry , Thermodynamics , Adsorption , Humans , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer/blood , Surface Properties
4.
Curr Drug Deliv ; 16(6): 490-499, 2019.
Article in English | MEDLINE | ID: mdl-31132975

ABSTRACT

BACKGROUND: The local anesthetic drugs, especially ropivacaine, were considered favorable analgesia for postoperative management because of their effective local pain relief and low adverse effects. However, the short half-life and the resulting in bolus doses lead to the indistinctive improvement of these drugs in postoperative pain relief. Therefore, the ropivacaine microspheres with sustained release and low initial burst release were anticipated. METHODS: Three methods including oil in water (O/W), water in oil in water (W/O/W), and solid in oil in water (S/O/W) emulsion solvent evaporation method were used to optimize the ropivacaine loaded PLGA microspheres. The microspheres were evaluated both in vitro and in rats. The in vitro-in vivo correlation (IVIVC) was also investigated. RESULTS: The microspheres prepared by O/W method showed more satisfactory properties and the microspheres used for evaluation were prepared by O/W method. The particle size, drug loading, encapsulation efficiency and burst release were 11.19±1.24 µm, 28.37±1.15%, 98.15±3.98%, and 10.96±5.37% for microspheres with PLGA of 12 kDa, and 6.64±0.61 µm, 19.62±0.89%, 92.74±4.21%, and 18.42±5.12% for microspheres with PLGA of 8 kDa, respectively. These microspheres were also injected into rats by subcutaneous, intramuscular and intraperitoneal route, respectively. It was indicated that the detectable concentration of ropivacaine could last for at least 20 days for both kinds of microspheres in spite of injection routes. The low burst releases at 1 d were also manifested in rats and they were 6.62%, 6.99%, 6.48% for the microspheres with PLGA of 12 kDa, and 4.72%, 4.33%, 4.48% for the microspheres with PLGA of 8 kDa by intraperitoneal, intramuscular and subcutaneous route, respectively. A linear relationship between the in vitro release and the in vivo adsorption of ropivacaine from microspheres was also established. CONCLUSION: The ropivacaine microspheres with sustained release and low burst release were acquired, which indicated that the postoperative pain relief might last longer and the side effects might get lower. Therefore, the ropivacaine microspheres prepared in this paper have great potential for clinical use.


Subject(s)
Microspheres , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Ropivacaine/pharmacokinetics , Animals , Drug Liberation , Oils/chemistry , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer/blood , Rats , Rats, Sprague-Dawley , Ropivacaine/blood , Ropivacaine/chemistry , Surface Properties , Water/chemistry
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