Poly Lactide-coglycolide Nanoparticles Research Articles

Modeling the Drug delivery Lifecycle of PLG Nanoparticles Using Intravital Microscopy.

Polylactide-co-glycolide (PLG) nanoparticles hold immense promise for cancer therapy due to their enhanced efficacy and biodegradable matrix structure. Understanding their interactions with blood cells and subsequent biodistribution kinetics is crucial for optimizing their therapeutic potential. In this study, three doxorubicin-loaded PLG nanoparticle systems are synthesized and characterized, analyzing their size, zeta potential, morphology, and in vitro release behavior. Employing intravital microscopy in 4T1-tumor-bearing mice, real-time blood and tumor distribution kinetics are investigated. A mechanistic pharmacokinetic model is used to analyze biodistribution kinetics. Additionally, flow cytometry is utilized to identify cells involved in nanoparticle hitchhiking. Following intravenous injection, PLG nanoparticles exhibit an initial burst release (<1min) and rapidly adsorb to blood cells (<5min), hindering extravasation. Agglomeration leads to the clearance of one carrier species within 3min. In stable dispersions, drug release rather than extravasation remains the dominant pathway for drug elimination from circulation. This comprehensive investigation provides valuable insights into the interplay between competing kinetics that influence the lifecycle of PLG nanoparticles post-injection. The findings advance the understanding of nanoparticle behavior and lay the foundation for improved cancer therapy strategies using nanoparticle-based drug delivery systems.

A feasible strategy of fabricating hybrid drugs encapsulated polymeric nanoparticles for the treatment of gastric cancer therapy

Chemotherapy of hybrid-drugs has become one of the widely used therapies for the prevention of cancers with promising clinical results. This study aimed to create compostable polymeric nanoparticles (PPNPs) for the codelivery of capsaicin (CAPS) and biotin (BT) and to examine the anticancer activity of the drug delivery mechanism (CAPS/BT@PPNPs) against in vitro and in vivo gastric cancer cells. Because of the insufficiency of double antitumor drugs BT and CAPS compressed in polymer-based bio-degradable nanoparticles, the encapsulation of BT and CAPS antitumor drugs co-loaded with polyethylene glycol and polylactidecoglycolide nanoparticles (PPNPs) is effective. Transmission electron microscopy (TEM) was utilized to investigate the structure of BT@PPNPs, CAPS@PPNPs, and BT/CAPS@PPNPs, as well as their shape and size. Human gastric carcinoma cell lines, such as SGC-791 and NCI-N87, were also induced to apoptosis in vitro by BT/CAPS@PPNPs. Morphologies and cell death were observed using bio-chemical staining methods, AO/EB (acridine orange/ethidium bromide) and Hoechst. Flow cytometry in dual staining was also used to confirm the mechanistic investigations of apoptosis. Overall, this dual drug delivery strategy suggests that BT/CAPS@PPNPs could be used as a new method to increase the efficacy of gastric therapeutics.

Glioblastoma Break-in; Try Something New

Context: Glioblastoma is the most invasive brain tumor with a poor prognosis and rapid progression. The standard therapy (surgical resection, adjuvant chemotherapy, and radiotherapy) ensures survival only up to 18 months. In this article, we focus on innovative types of radiotherapy, various combinations of temozolomide with novel substances, and methods of their administration and vector delivery to tumor cells. Evidence Acquisition: For a detailed study of the various options for chemotherapy and radiotherapy, Elsevier, NCBI MedLine, Scopus, Google Scholar, Embase, Web of Science, The Cochrane Library, EMBASE, Global Health, CyberLeninka, and RSCI databases were analyzed. Results: The most available method is oral or intravenous administration of temozolomide. More efficient is the combined chemotherapy of temozolomide with innovative drugs and substances such as lomustine, histone deacetylase inhibitors, and chloroquine, as well as olaparib. These combinations improve patient survival and are effective in the treatment of resistant tumors. Compared to standard fractionated radiotherapy (60 Gy, 30 fractions, 6 weeks), hypofractionated is more effective for elderly patients due to lack of toxicity; brachytherapy reduces the risk of glioblastoma recurrence, while radiosurgery with bevacizumab is more effective against recurrent or inoperable tumors. Currently, the most effective treatment is considered to be the intranasal administration of anti-Ephrin A3 (anti-EPHA3)-modified containing temozolomide butyl ester-loaded (TBE-loaded) poly lactide-co-glycolide nanoparticles (P-NPs) coated with N-trimethylated chitosan (TMC) to overcome nasociliary clearance. Conclusions: New radiotherapeutic methods significantly increase the survival rates of glioblastoma patients. With some improvement, it may lead to the elimination of all tumor cells leaving the healthy alive. New chemotherapeutic drugs show impressive results with adjuvant temozolomide. Anti-EPHA3-modified TBE-loaded P-NPs coated with TMC have high absorption specificity and kill glioblastoma cells effectively. A new “step forward” may become a medicine of the future, which reduces the specific accumulation of nanoparticles in the lungs, but simultaneously does not affect specific absorption by tumor cells.

Engineering of hybrid anticancer drug-loaded polymeric nanoparticles delivery system for the treatment and care of lung cancer therapy

Chemotherapy with combination drugs has become one of the most commonly used cancer prevention treatments, with positive clinical results. The goal of this study was to develop compostable polymeric nanomaterials (NMs) for the delivery of puerarin (PRN) and 5-fluorouracil (5FU), as well as to investigate the anticancer activity of the drug delivery system (PRN-5FU NMs) against in vitro and in vivo lung cancer cells. Since double antitumor drugs PRN and 5FU are insufficiently compressed in polymer-based bio-degradable nanoparticles, encapsulation of PRN and 5FU antitumor drugs were co-encapsulated with polyethylene glycol and polylactidecoglycolide nanoparticles (NMs) is efficient. The arrangement of PRN NMs, 5FU NMs, and PRN-5FU NMs, as well as the nanoparticles shape and scale, were studied using transmission electron microscopy (TEM). 5FU-PRN NMs triggered apoptosis in lung carcinoma cell lines such as HEL-299 and A549 in vitro. Acridine orange/ethidium bromide (AO/EB) and nuclear damaging staining techniques were used to observe morphologies and cell death. The mechanistic analysis of apoptosis was also confirmed by flow cytometry analysis using dual staining. When compared to free anticancer products, the hemolysis analysis findings of the 5FU-PRN NMs showed excellent biocompatibility. Taken together the advantages, this combination drug conveyance strategy exposed that 5FU-PRN NMs could have a significant promising to improve the effectiveness of lung cancer cells.

Nanoparticle-Based Oral Drug Delivery System for an Injectable Antibiotic – Streptomycin

Background: To develop an oral drug delivery system for an injectable antibiotic, streptomycin. Methods: Poly-lactide-co-glycolide (PLG) nanoparticles encapsulating streptomycin were prepared by the multiple emulsion technique and administered orally to mice for biodistribution and chemotherapeutic studies. Results: The mean particle size was 153.12 nm with 32.12 ± 4.08% drug encapsulation and 14.28 ± 2.83% drug loading. Streptomycin levels were maintained for 4 days in the plasma and for 7 days in the organs following a single oral administration of PLG nanoparticles. There was a 21-fold increase in the relative bioavailability of PLG-encapsulated streptomycin compared with intramuscular free drug. In Mycobacterium tuberculosis H₃₇Rv infected mice, eight doses of the oral streptomycin formulation administered weekly were comparable to 24 intramuscular injections of free streptomycin. Further, the nanoparticle formulation did not result in nephrotoxicity as assessed on a biochemical basis. Conclusion: Our results suggest that nanoencapsulation might be useful for developing a suitable oral dosage form for streptomycin and perhaps for other antibiotics that are otherwise injectable.

Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolized antitubercular drug carriers for treatment of tuberculosis.

This study was carried out to explore lectin-functionalized poly (lactide-co-glycolide) nanoparticles (PLG-NPs) as bioadhesive drug carriers against tuberculosis (TB), in order to reduce the drug dosage frequency of antitubercular drugs and thus improve patient compliance in TB chemotherapy. Wheat germ agglutinin (WGA)-coated PLG-NPs were prepared by a two-step carbodiimide procedure. This formulation was administered to guinea pigs through the oral/aerosol route for a detailed pharmacokinetic and chemotherapeutic evaluation. Immunological or hepatotoxic effects of WGA lectin, if any, were also determined. WGA-functionalized PLG-NPs were in the size range of 350-400 nm, with binding of 3-3.5 microg of WGA/mg of PLG-NPs and drug encapsulation efficiency of 54%-66%. Upon administration of lectin-coated PLG-NPs through the oral/aerosol route, the presence of drugs in plasma was observed for 6-7 days for rifampicin and 13-14 days for isoniazid and pyrazinamide. However, upon administration of uncoated PLG-NPs (oral/aerosolized) rifampicin was detectable in plasma for 4-6 days, whereas isoniazid and pyrazinamide were detectable for 8-9 days. All three drugs were present in lungs, liver and spleen for 15 days. Administration of WGA-coated PLG-NPs caused a significant (P < 0.001) increase in the relative bioavailability of antitubercular drugs. Chemotherapeutic studies revealed that three doses of oral/nebulized lectin-coated nanoparticles fortnightly could yield undetectable mycobacterial colony forming units (cfu); this was achievable with 45 doses of oral free drugs. WGA-functionalized PLG-NPs could be potential drug carriers for antitubercular drugs through the oral as well as aerosol route for effective TB control.