Abstract
Supercritical carbon dioxide (SC-CO2) can serve as solvent, anti-solvent and solute, among others, in the field of drug delivery applications, e.g., for the formulation of polymeric nanocarriers in combination with different drug molecules. With its tunable properties above critical pressure and temperature, SC-CO2 offers control of the particle size, the particle morphology, and their drug loading. Moreover, the SC-CO2-based techniques overcome the limitations of conventional formulation techniques e.g., post purification steps. One of the widely used polymers for drug delivery systems with excellent mechanical (Tg, crystallinity) and chemical properties (controlled drug release, biodegradability) is poly (lactic acid) (PLA), which is used either as a homopolymer or as a copolymer, such as poly(lactic-co-glycolic) acid (PLGA). Over the last 30 years, extensive research has been conducted to exploit SC-CO2-based processes for the formulation of PLA carriers. This review provides an overview of these research studies, including a brief description of the SC-CO2 processes that are widely exploited for the production of PLA and PLGA-based drug-loaded particles. Finally, recent work shows progress in the development of SC-CO2 techniques for particulate drug delivery systems is discussed in detail. Additionally, future perspectives and limitations of SC-CO2-based techniques in industrial applications are examined.
Highlights
The targeted treatment of diseases with drug-loaded carriers is becoming a substantial reality in clinical practice [1]
This review provides an overview of these research studies, including a brief description of the SC-CO2 processes that are widely exploited for the production of polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA)-based drug-loaded particles
This review provides an overview of PLA/PLGA-based drug delivery particle systems produced with SC-CO2 techniques till the present date (November 2020), including a detailed description of the latest studies published since 2014 with details of polymer characteristics, encapsulated drugs, and rationales of the studies
Summary
The targeted treatment of diseases with drug-loaded carriers is becoming a substantial reality in clinical practice [1]. This review describes the properties and applications of SC-CO2 as solvent, anti-solvent, and extraction compound for the production of drug-loaded particles, focusing on poly (lactic acid) (PLA) and its copolymer system, poly (lactide-co-glycolide) (PLGA) These are among the most established polymers in the pharmaceutical field [12,13]. PLA can directly be synthesized via different methods such as polycondensation, ring-opening polymerization or enzymatic polymerization of the lactic acid monomer, whereby the ring-opening polymerization provides the best control over the polymerization, yielding higher molar mass PLA [16] The latter allows tuning the stereo-chemistry of the L- and D- forms in the final polymer, which influences the molar mass and dispersity, the mechanical and thermal properties of PLA, crystallinity, and the degradation behavior [16]. This review provides an overview of PLA/PLGA-based drug delivery particle systems produced with SC-CO2 techniques till the present date (November 2020), including a detailed description of the latest studies published since 2014 with details of polymer characteristics, encapsulated drugs, and rationales of the studies
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