Paclitaxel delivery system based on poly(lactide-co-glycolide) microparticles and chitosan thermo-sensitive gel for mammary adenocarcinoma treatment.

OBJECTIVES: To evaluate the combination of more than one release system in the same formulation as a useful strategy to achieve paclitaxel delivery in a more sustained and controlled manner. METHODS: The present study deals with the preparation of poly(lactide-co-glycolide) microparticles loaded with paclitaxel and included in a chitosan thermo-sensitive gelling solution. The microparticles were characterized by their size, shape and drug loading. The formulation was characterized by scanning electron microscopy, in vitro release experiments and was evaluated in mice bearing mammary adenocarcinoma. KEY FINDINGS: The formation of paclitaxel crystals in a pharmaceutical formulation reduces its efficacy. In this work, the use of microparticles avoided this phenomenon. Combining more than one delivery system allowed delivering paclitaxel in a more sustained and controlled manner leading to a long-term effect in the site of action. The formulation showed an inhibition in tumour volume of 63.0% in comparison with the control group. CONCLUSIONS: One intratumour injection of gelling solution containing the microparticles was at least as efficacious as four intraperitoneal injections of a commercial formulation. In addition, the delivery system was nontoxic, and the treated mice presented the highest percentage of tumour regression and median survival time.

Preparation of TPP-crosslinked chitosan microparticles by spray drying for the controlled delivery of progesterone intended for estrus synchronization in cattle.

PURPOSE: Planned reproduction in cattle involves regulation of estrous cycle and the use of artificial insemination. Cycle control includes the administration of exogenous progesterone during 5-8 days in a controlled manner allowing females to synchronize their ovulation. Several progesterone delivery systems are commercially available but they have several drawbacks. The aim of the present contribution was to evaluate chitosan microparticles entrapping progesterone as an alternative system. METHODS: Microparticles were prepared by spray drying. The effect of formulation parameters and experimental conditions on particle features and delivery was studied. A mathematical model to predict progesterone plasma concentration in animals was developed and validated with experimental data. RESULTS: Microparticle size was not affected by formulation parameters but sphericity enhances as Tween 80 content increases and it impairs as TPP content rises. Z potential decreases as phosphate content rises. Particles remain stable in acidic solution but the addition of surfactant is required to stabilize dispersions in neutral medium. Encapsulation efficiencies was 69-75%. In vitro delivery studies showed burst and diffusion-controlled phases, being progesterone released faster at low pH. In addition, delivery extend in cows was affected mainly by particle size and hormone initial content, while the amount injected altered plasma concentration. Theoretical predictions with excellent accuracy were obtained. CONCLUSION: The mathematical model developed can help to find proper particle features to reach specific delivery rates in the animals. This not only save time, money and effort but also minimized experimentation with animals which is desired from an ethical point of view.

Effect of particle size, polydispersity and polymer degradation on progesterone release from PLGA microparticles: Experimental and mathematical modeling.

Poly(lactic-co-glycolic acid) (PLGA) microparticles containing progesterone were prepared by the solvent extraction/evaporation and microfluidic techniques. Microparticles were characterized by their size distribution, encapsulation efficiency, morphology and thermal properties. The effect of particle size, polydispersity and polymer degradation on the in vitro release of the hormone was studied. A triphasic release profile was observed for larger microparticles, while smaller microspheres showed a biphasic release profile. This behavior is related to the fact that complete drug release was achieved in a few days for smaller microparticles, during which polymer degradation effects are still negligible. A mathematical model was developed that predicts the progesterone release profiles from different-sized PLGA microspheres. The model takes into account both the dissolution and diffusion of the drug in the polymeric matrix as well as the autocatalytic effect of polymer degradation. The model was adjusted and validated with novel experimental data. Simulation results are in very good agreement with experimental results.