Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method

Abstract

Background: Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Methods: Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. Results: The nanoparticles prepared in this study were spherical, with an average particle size of 85-424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) . oil/oil (5.5%) . water/oil/water (4.7%) . modified oil/water (4.1%) . nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Conclusion: Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug.

The Effect of Local Delivery Doxycycline and Alendronate on Bone Repair

“…PLGA provides a wide range of advantages, such as a smaller particle size that facilitates penetration into the cells, higher entrapment efficiency for increased drug release, lower minimum inhibitory concentration, and minimum bacterial concentrations, meaning that a better antibacterial activity was achieved with a smaller amount of drug (30,31). The present study provided evidence that a PLGA showed an interaction with bone repair when it was used as a filling material in bone defects.…”

“…The author explained this result by the high concentration (10%) of doxycycline in the preparation. However, the present study showed positive results with this concentration, probably due to the drug administration by the vehicle-PLGA, which decreased the high concentration and reduced contact between the tissue and drugs (30,31). The 10% of doxycycline has been used in several commercially available agents with positive results in bone formation (38) and alendronate can be applied topically in lower doses to locally inhibit bone resorption (39).…”

“…In the present study, it was hypothesized that association of the anabolic properties of alendronate (12) with the antibiotic and anti-proteolytic properties of doxycycline (29) combined with the delivery system of PLGA (30,31) would increase bone neoformation and accelerate bone repair. The null hypothesis tested was that local delivery of 10% doxycycline and 1% alendronate in PLGA would not affect the repair of experimental bone defects in rats at 7 and 15 days.…”

Physicochemical Properties and Control Release of Aloe Vera (Aloe barbadensis Miller) Bioactive Loaded Poly (Lactic Co-Glycolide Acid) Synthesized Nanoparticles

“…Nanoparticles synthesize with polymers such as Poly (Lactic co-Glycolide Acid) were reported to have a high EE due to its molecular structure that is associated to its active sites [17]. An EE of 47.6% and 38.9% for cinnamon bark extract loaded in PLGA-50 and PLGA-65 NP, respectively was reported by Hill et al [18].…”

Enabling nanomaterial, nanofabrication and cellular technologies for nanoneuromedicines

“…36,37 The molecular weight of the polymer can be varied to marginally control the release of payload. 35,36,38 Coating the PLGA surface with hydrophobic materials, like gelatin or chitosan 34 , can decrease the initial drug burst and extend the release period. The rapid degradation of polyester products occurs in microenvironments with a low pH (1.5 – 3.6), 39,40 which can be problematic when the therapeutic payload is denatured in parallel.…”