Mesoporous Silicon‐PLGA Composite Microspheres for the Double Controlled Release of Biomolecules for Orthopedic Tissue Engineering

Abstract

In this study, poly(dl-lactide-co-glycolide)/porous silicon (PLGA/pSi) composite microspheres, synthesized by a solid-in-oil-in-water (S/O/W) emulsion method, are developed for the long-term controlled delivery of biomolecules for orthopedic tissue engineering applications. Confocal and fluorescent microscopy, together with material analysis, show that each composite microsphere contained multiple pSi particles embedded within the PLGA matrix. The release profiles of fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (FITC-BSA), loaded inside the pSi within the PLGA matrix, indicate that both PLGA and pSi contribute to the control of the release rate of the payload. Protein stability studies show that PLGA/pSi composite can protect BSA from degradation during the long term release. We find that during the degradation of the composite material, the presence of the pSi particles neutralizes the acidic pH due to the PLGA degradation by-products, thus minimizing the risk of inducing inflammatory responses in the exposed cells while stimulating the mineralization in osteogenic growth media. Confocal studies show that the cellular uptake of the composite microspheres is avoided, while the fluorescent payload is detectable intracellularly after 7 days of co-incubation. In conclusion, the PLGA/pSi composite microspheres offer an additional level of controlled release and could be ideal candidates as drug delivery vehicles for orthopedic tissue engineering applications.

The effect of multistage nanovector targeting of VEGFR2 positive tumor endothelia on cell adhesion and local payload accumulation

“…During systemic administration MSV demonstrated rapid (< 1 hour) tumoritropic accumulation independent of EPR [25, 26] and enhanced delivery to the bone marrow upon targeting with E-selectin [27]. The nanosized pores and increased surface area of MSV can accommodate a variety of payloads (e.g., chemotherapeutics [28, 29], drugs [30], NP [31], contrast agents [32], biologics [33]) and their release could be tuned by adjusting the pore size [34] or their surface coating [35–37]. Furthermore the loading of payloads into the nanopores, resulting in nanoconfinement, enabled the emergence of features at the nanoscale bestowing MSV with enhanced gene silencing, hyperthermia, and diagnostic potential [31, 38].…”

Microfluidic interactions between red blood cells and drug carriers by image analysis techniques

“…For its suitability and long clinical experience, PLGA, can be considered the most popular biodegradable polymer. Various polymeric devices like microspheres, microcapsules, nanoparticles, pellets, implants and films have been fabricated using these polymer (Cheng et al, 2007;Esmaeili et al, 2008;Fan et al, 2012;Houchin and Topp, 2009;Li et al, 2001;Makadia and Siegel, 2011;Wischke and Schwendeman, 2008). PLGA has been mostly formulated into delivery systems for vehicle different drug classes, such as vaccines, peptides, proteins and micro-molecules (Li et al, 2001).…”

Physicochemical Properties Affect the Synthesis, Controlled Delivery, Degradation and Pharmacokinetics of Inorganic Nanoporous Materials

“…In addition, the release of payloads from pSi can be modulated using a 'capping' or 'gate-keeping' approach. For example, pSi can be capped with poly(l-lactide) [58], poly(dl-lactide-co-glycolide) [59], agarose [60], cellular membranes [61] and hydrogels [62] allowing for the release of proteins and chemotherapeutics or act as sensors. Furthermore, these approaches enable a responsive drug delivery platform capable of delivering payloads in response to variations in temperature [63], voltage [64], proteases [65] and pH [66].…”