Impact of PEG Content on Doxorubicin Release from PLGA-co-PEG Nanoparticles.

Nanoparticles (NPs) have become attractive vehicles for drug delivery in cancer therapy due to their ability to accumulate in tumours and mitigate side effects. This study focuses on the production of doxorubicin (DOX)-loaded NPs comprising Poly (lactic-co-glycolic acid)-Polyethylene glycol with varying PEG proportions and the examination of their impact on drug release kinetics. DOX-loaded NPs, composed of PLGA-co-PEG with PEG contents of 0%, 5%, 10%, and 15%, were synthesized by the solvent evaporation technique, exhibited spherical morphology, and had sizes ranging from 420 nm to 690 nm. In vitro drug release studies revealed biphasic profiles, with higher PEG contents leading to faster and more extensive drug release. The Baker-Lonsdale model demonstrated the best fit to the drug release data, indicating that the release process is diffusion-controlled. The diffusion coefficients for DOX determined ranged from 6.3 × 10-18 to 7.55 × 10-17 cm2s-1 and exhibited an upward trend with increasing PEG content in the polymer. In vitro cytotoxicity tests with CHO cells showed that unloaded NPs are non-toxic, while DOX-loaded PLGA-PEG 15% NPs induced a greater decrease in cellular viability compared to their PLGA counterparts. A mathematical relationship between the diffusion coefficient and PEG percentage was derived, providing a practical tool for optimizing DOX release profiles.

Double-Walled Poly-(D,L-lactide-co-glycolide) (PLGA) and Poly(L-lactide) (PLLA) Nanoparticles for the Sustained Release of Doxorubicin.

Double-walled nanoparticles (DWNPs), containing doxorubicin as a model drug, were produced using poly-(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by the solvent evaporation technique. Double-walled microparticles containing doxorubicin were also produced to make possible the examination of the inner morphology and drug distribution using optical and fluorescence microscopy. The produced microparticles present a double-walled structure with doxorubicin solubilized in the PLGA-rich phase. The DWNPs produced present very low initial burst values and a sustained DOX release for at least 90 days with release rates decreasing with the increase in the PLLA amount. Zero-order release kinetics were obtained after day 15. The results support that the PLLA layer acts as a rate control barrier and that the diffusion of doxorubicin from the drug-loaded inner PLGA core can be retarded by an increase in the thickness of the unloaded outer layer. The unloaded double-walled nanoparticles produced were used in in vitro tests with CHO cells and demonstrate that they are nontoxic, while the double-walled nanoparticles loaded with doxorubicin caused a great cellular viability and decreased when tested in vitro.

Doxorubicin-loaded galactose-conjugated poly(d,l-lactide-co-glycolide) nanoparticles as hepatocyte-targeting drug carrier.

The objective of this work is to produce doxorubicin-loaded galactose-conjugated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to be specifically recognised by human hepatoma cellular carcinoma (Hep G2) cells and assess NPs cytotoxicity. Doxorubicin-unloaded and doxorubicin-loaded galactose-conjugated PLGA NPs were prepared using an emulsion method and characterised for morphology, size, drug release behaviour, Hep G2 recognition and cell cytotoxicity. The produced doxorubicin-loaded PLGA-galactose-conjugate nanoparticles (PLGA-GAL NPs) are spherical in shape with a size of 365 ± 74 nm, a drug encapsulation efficiency of 69% and released in a biphasic pattern with higher release rates at pH 5. In vitro cell studies confirmed the specific interaction between the receptors of Hep G2 and the PLGA-GAL NPs. Cell cytotoxicity tests showed that unloaded NPs are non-toxic and that doxorubicin-loaded NPs caused a cellular viability decrease of around 80%, therefore representing a promising approach to improve liver-specific drug delivery.

Anti-CD8 conjugated nanoparticles to target mammalian cells expressing CD8.

This work aimed at the development of targeted drug delivery systems using nanoparticles fused with antibodies. The antibody anti-human CD8 was coupled onto PLGA nanoparticles, and the ability of these particles to specifically target cells expressing CD8 was studied. The obtained particles were found to be of spherical shape exhibiting a size between 350 and 600 nm. In vitro experiments with different cellular cultures (TE671, CHO and HEK293) using unmodified nanoparticles containing rhodamine have shown that particles were present on their surface within 48 h of incubation. In vitro tests using anti-CD8 conjugated nanoparticles in CHO cell cultures indicated that all transfected cells which express CD8 show these particles on their surface within 1h of incubation. These results demonstrated that, in a shorter time, the produced particles can target cells expressing CD8 on their surface which offers the ability to reduce drug side effects. The antibody-coupled nanoparticles represent a promising approach to improve the efficacy of active targeting for lymphoblastic leukaemia therapy.