Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

In the paper

“Solvent casting is a method to fabricate a macroscopic millimeter size formulation which can be implanted or inserted for long term medication [59].”

What the sources say

• Partly supported

  The Materials and Methods (page not given) describe solvent casting risperidone and polymer, then molding or extruding the film into implantable pellets or rods. The Introduction and Conclusions describe long-term drug delivery, but the passages do not specify millimeter-sized dimensions; the demonstrated use is a risperidone implant in mice, not a general formulation for long-term medication. (LLM, conf=0.81)

  cites [59] Rabin, 2008, In vitro and in vivo demonstration of risperidone implants in mice, Schizophr. Res. sourceExperimental — accuracy not yet measured

In the paper

“PLGA/PEG block copolymers have been processed as diblock (PLGA-PEG) [18,19] or triblock molecules with both ABA (PLGA-PEG-PLGA) [20] and BAB (PEG-PLGA-PEG) [21] types.”

What the sources say

• Supported

  The citation to this paper is attached to the diblock (PLGA-PEG) portion of the sentence, not the triblock types. Sections 2.2.1 and 3.1 describe synthesizing PLGA-b-PEG by conjugating a PLGA block with a PEG block. (LLM, conf=0.94)

  cites [18] Cheng, 2007, Formulation of functionalized PLGA-PEG Nanoparticles for in vivo targeted drug delivery, Biomaterials source
• ?Not checked — no full text of the sourcecites [19] Li, 2001, PEGylated PLGA nanoparticles as protein carriers: Synthesis, preparation and biodistribution in rats, J. Control. Release source
• ?Not checked — no full text of the sourcecites [20] Ghahremankhani, 2007, PLGA-PEG-PLGA tri-block copolymers as an in-situ gel forming system for calcitonin delivery, Polym. Bull. source
• ?Not checked — no full text of the sourcecites [21] Jeong, 2000, In situ gelation of PEGPLGAPEG triblock copolymer aqueous solutions and degradation thereof, J. Biomed. Mater. Res. source

In the paper

“Unlike solvent-casting, extrusion is a continuous process of drawing polymer-drug mixture through a die to create implants of fixed cross-sectional profile without any use of solvent.”

What the sources say

• Supported

  The Discussion describes extrusion, in contrast to solvent-casting, as a continuous, solvent-free process for making drug implants. Materials and Methods > Extrusion describes feeding a polymer–drug mixture through an extruder die to produce rods, consistent with the claimed fixed cross-sectional profile. (LLM, conf=0.90)

  cites [61] Wang, 2010, A rapid method for creating drug implants: Translating laboratory-based methods into a scalable manufacturing process, J. Biomed. Mater. Res. Part B Appl. Biomater. source

In the paper

“PLGA are a family of FDA-approved biodegradable polymers that are physically strong and highly biocompatible and have been extensively studied as delivery vehicles for drugs, proteins and various other macromolecules such as DNA, RNA and peptides [1–3].”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Bouissou, 2006, The influence of surfactant on PLGA microsphere glass transition and water sorption: Remodeling the surface morphology to attenuate the burst release, Pharm. Res. source
• ?Not checked — no full text of the sourcecites [2] Jain, 2000, The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices, Biomaterials source
• ?Not checked — no full text of the sourcecites [3] Ruhe, 2003, rhBMP-2 release from injectable poly (DL-lactic-co-glycolic acid)/calcium-phosphate cement composites, J. Bone Jt. Surg. source

In the paper

“PLGA are a family of FDA-approved biodegradable polymers that are physically strong and highly biocompatible and have been extensively studied as delivery vehicles for drugs, proteins and various other macromolecules such as DNA, RNA and peptides [1–3].”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Bouissou, 2006, The influence of surfactant on PLGA microsphere glass transition and water sorption: Remodeling the surface morphology to attenuate the burst release, Pharm. Res. source
• ?Not checked — no full text of the sourcecites [2] Jain, 2000, The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices, Biomaterials source
• ?Not checked — no full text of the sourcecites [3] Ruhe, 2003, rhBMP-2 release from injectable poly (DL-lactic-co-glycolic acid)/calcium-phosphate cement composites, J. Bone Jt. Surg. source

In the paper

“Salting out is another method in which a water-in-oil emulsion is first formed containing polymer, solvent (usually non chlorinated like acetone), salt (e.g., magnesium acetate tetrahydrate) and stabilizer. Water is then added to the solution until the volume is sufficient to diffuse acetone into the water, resulting in nanoparticle formulations [55–58].”

What the sources say

• ?Not checked — no full text of the sourcecites [55] Lamprecht, 2000, Influences of process parameters on nanoparticle preparation performed by a double emulsion pressure homogenization technique, Int. J. Pharm. source
• ?Not checked — no full text of the sourcecites [56] Murakami, 1999, Preparation of poly(D,L-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method, Int. J. Pharm. source
• ?Not checked — no full text of the sourcecites [57] Konan, 2003, Preparation and characterization of sterile sub-200 nm meso-tetra(4-hydroxylphenyl)porphyrin-loaded nanoparticles for photodynamic therapy, Eur. J. Pharm. Biopharm. source
• ?Not checked — no full text of the sourcecites [58] Kwon, 2001, Preparation of PLGA nanoparticles containing estrogen by emulsification-diffusion method, Colloids Surf. A Physicochem. Eng. Asp. source

In the paper

“The main disadvantage of this process is the adhesion of the microparticles to the inner walls of the spray-dryer.”

In the paper

“A modification on this procedure called the double or multiple emulsion technique has become the favored protocol for encapsulating hydrophilic compounds and proteins [37].”

What the sources say

• ?Not checked — no full text of the sourcecites [37] Mao, 2007, Effect of WOW process parameters on morphology and burst release of FITC-dextran loaded PLGA microspheres, Int. J. Pharm. source

In the paper

“It is soluble in wide range of common solvents including chlorinated solvents, tetrahydofuran, acetone or ethyl acetate [7,10].”

What the sources say

• ?Not checked — no full text of the sourcecites [7] Uhrich, 1999, Polymeric systems for controlled drug release, Chem. Rev. source
• ?Not checked — no full text of the sourcecites [10] Wu, 2001, Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid polymers. Part II: Biodegradation, J. Biomater. Sci. Polym. Ed. source

In the paper

“Additionally, microfluidic devices can incorporate the use of electrostatic forces to control the size and shape of particles for increased tuning of release characteristics [53].”

What the sources say

• ?Not checked — no full text of the sourcecites [53] Loscertales, 2002, Micro/Nano encapsulation via electrified coaxial liquid jets, Science source

In the paper

“Nanoparticles can also be synthesized by nanoprecipitation methods. Polymer and drug are dissolved in acetone and added to an aqueous solution containing Pluronic F68. The acetone is evaporated at appropriate temperatures and reduced pressures leaving behind the polymer encapsulated nanoparticles with drug [54].”

What the sources say

• ?Not checked — no full text of the sourcecites [54] Hans, 2002, Biodegradable nanoparticles for drug delivery and targeting, Curr. Opin. Solid State Mater. Sci. source

In the paper

“Drug delivery of peptides and proteins may also require parenteral formulations to avoid degradation in the digestive tract and first pass metabolism, while the short circulating half-lives of peptides and proteins contribute to the need for parenteral formulations that will reduce dosing frequency.”

In the paper

“Presence of methyl side groups in PLA makes it more hydrophobic than PGA and hence lactide rich PLGA copolymers are less hydrophilic, absorb less water and subsequently degrade more slowly.”

In the paper

“Alternatively, spray drying is very rapid, convenient and has very few processing parameters, making it suitable for industrial scalable processing.”

In the paper

“The copolymer is usually a free flowing solution at low temperature and can form a high viscosity gel at body temperature.”

In the paper

“Mechanical strength, swelling behavior, capacity to undergo hydrolysis and subsequently biodegradation rate of the polymer are directly influenced by the degree of crystallinity of the PLGA, which is further dependent on the type and molar ratio of the individual monomer components in the copolymer chain.”

In the paper

“Emulsion techniques require precise control of processing parameters for higher encapsulation efficiency, and phase separation techniques tend to produce agglomerated particles and also require removal of large quantities of the organic phase from the microspheres. This makes the process difficult for mass production.”

In the paper

“Degree of crystallinity and melting point of the polymers are directly related to the molecular weight of the polymer.”

In the paper

“Biocompatibility is clearly important, although it is important to note that biocompatibility is not an intrinsic property of a material, but depends on the biological environment and the tolerability that exists with respect to specific drug-polymer-tissue interactions [9].”

What the sources say

• ?Not checked — no full text of the sourcecites [9] Anderson, 1997, Biodegradation and biocompatibility of PLA and PLGA microspheres, Adv. Drug Deliv. Rev. source

In the paper

“Recently, coaxial capillary flows have become a preferable technique to produce monodispersed micro/nanoparticles with either simple or core-shell structure because of their precise control on mean particle size [50,51].”

What the sources say

• ?Not checked — no full text of the sourcecites [50] Barrero, 2007, Micro- and nanoparticles via capillary flows, Annu. Rev. Fluid Mech. source
• ?Not checked — no full text of the sourcecites [51] Freitas, 2005, Microencapsulation by solvent extraction/evaporation: Reviewing the state of the art of microsphere preparation process technology, J. Control. Release source

In the paper

“Drugs formulated in such polymeric devices are released either by diffusion through the polymer barrier, or by erosion of the polymer material, or by a combination of both diffusion and erosion mechanisms.”

In the paper

“As a rule, higher content of PGA leads to quicker rates of degradation with an exception of 50:50 ratio of PLA/PGA, which exhibits the fastest degradation, with higher PGA content leading to increased degradation interval below 50%.”

In the paper

“The degradation of the PLGA carriers is quick on the initial stage (around 30%) and slows eventually to be cleared by respiration in the lung [16].”

What the sources say

• ?Not checked — no full text of the sourcecites [16] Bazile, 1992, Body distribution of fully biodegradable [14C]-poly(lactic acid) nanoparticles coated with albumin after parenteral administration to rats, Biomaterials source

In the paper

“This method is known to encapsulate all kinds of drugs/peptides/proteins into microparticles without significant loss in their biological activity.”

In the paper

“Crystalline PGA, when co-polymerized with PLA, reduces the degree of crystallinity of PLGA and as a result increase the rate of hydration and hydrolysis.”

In the paper

“Triblock copolymers of both ABA and BAB type can act as a thermogel with an A-block covalently coupled with a B-block via ester link.”

In the paper

“The Tg (glass transition temperature) of the PLGA copolymers are reported to be above the physiological temperature of 37 °C and hence are glassy in nature, thus exhibiting fairly rigid chain structure.”

In the paper

“The nature of solvent used, temperature of the solvent evaporation and feed rate affects the morphology of the microspheres.”

In the paper

“Water-in-oil-in-water emulsion methods are best suited to encapsulate water-soluble drugs like peptides, proteins, and vaccines, unlike single emulsion methods which is ideal for water-insoluble drugs like steroids.”

In the paper

“This layer of PEG acts as a barrier and reduces the interactions with foreign molecules by steric and hydrated repulsion, giving enhanced shelf stability [22].”

What the sources say

• ?Not checked — no full text of the sourcecites [22] Tobio, 1998, Stealth PLA-PEG nanoparticles as protein carriers for nasal administration, Pharm. Res. source

In the paper

“The role of enzymes in any PLGA biodegradation is unclear. Most literature indicate that the PLGA biodegradation does not involve any enzymatic activity and is purely through hydrolysis. However, some investigators have suggested an enzymatic role in PLGA breakdown based upon the difference in the in vitro and in vivo degradation rates.”

What the sources say

• ?Not checked — no full text of the sourcecites [80] Alexis, 2005, Factors affecting the degradation and drug-release mechanism of poly (lactic acid) and poly [(lactic acid)-co-(glycolic acid)], Polym. Int. source

In the paper

“Denatured species are therapeutically inactive and can cause unpredictable side effects, such as immunogenicity or other toxicity.”

What the sources say

• ?Not checked — no full text of the sourcecites [60] Widmer, 1998, Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration, Biomaterials source

In the paper

“At the moment, there are conflicting reports on the effect of crystallinity on the degradation rate [80].”

What the sources say

• ?Not checked — no full text of the sourcecites [80] Alexis, 2005, Factors affecting the degradation and drug-release mechanism of poly (lactic acid) and poly [(lactic acid)-co-(glycolic acid)], Polym. Int. source

In the paper

“The PLGA polymer biodegrades into lactic and glycolic acids. Lactic acid enters the tricarboxylic acid cycle and is metabolized and subsequently eliminated from the body as carbon dioxide and water [75]. Glycolic acid is either excreted unchanged in the kidney or it enters the tricarboxylic acid cycle and is eventually eliminated as carbon dioxide and water.”

What the sources say

• ?Not checked — no full text of the sourcecites [75] Crotts, 1998, Protein delivery from poly (lactic-co-glycolic acid) biodegradable microspheres: Release kinetics and stability issues, J. Microencapsul. source

In the paper

“After such pressurization and rapid depressurization sequence, the thermodynamic instability of CO2 molecules leads to their clustering inside the liquid polymer. As CO2 leaves, the emulsion results in a porous polymer structure [66,67].”

What the sources say

• ?Not checked — no full text of the sourcecites [66] Koushik, 2004, Preparation of large porous Deslorelin-PLGA microparticles with reduced residual solvent and cellular uptake using a supercritical carbon dioxide process, Pharm. Res. source
• ?Not checked — no full text of the sourcecites [67] Davies, 2008, Applications of supercritical CO2 in the fabrication of polymer systems for drug delivery and tissue engineering, Adv. Drug Deliv. Rev. source

In the paper

“PLGA 50:50 (PLA/PGA) exhibited a faster degradation than PLGA 65:35 due to preferential degradation of glycolic acid proportion assigned by higher hydrophilicity. Subsequently PLGA 65:35 shows faster degradation than PLGA 75:25 and PLGA 75:25 than PLGA 85:15 [79].”

What the sources say

• ?Not checked — no full text of the sourcecites [79] Park, 1995, Degradation of poly(lactic-co-glycolic acid) microspheres: Effect of copolymer composition, Biomaterials source

In the paper

“Third, solvent-casting and compression molding are not continuous processes, which may increase batch-to-batch variation in the composition of implants as well as cost of manufacturing [60].”

What the sources say

• ?Not checked — no full text of the sourcecites [60] Widmer, 1998, Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration, Biomaterials source

In the paper

“The ratio of surface area to volume has shown to be a significant factor for degradation of large devices. Higher surface area ratio leads to higher degradation of the matrix.”

What the sources say

• ?Not checked — no full text of the sourcecites [82] Schliecker, 2003, Hydrolytic degradation of poly(lactide-co-glycolide) films: Effect of oligomers on degradation rate and crystallinity, Int. J. Pharm. source
• ?Not checked — no full text of the sourcecites [86] Witt, 2001, Morphological characterization of microspheres, films and implants prepared from poly(lactide-co-glycolide) and ABA triblock copolymers: Is the erosion controlled by degradation, swelling or diffusion?, Eur. J. Pharm. Biopharm. source
• ?Not checked — no full text of the sourcecites [87] Grizzi, 1995, Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence, Biomaterials source

In the paper

“In general, the PLGA degradation and the drug release rate can be accelerated by greater hydrophilicity, increase in chemical interactions among the hydrolytic groups, less crystallinity and larger volume to surface ratio of the device.”

In the paper

“The first stage of drug release is through random scission of the polymer without any polymer weight loss and is mainly through diffusion, while the second stage is characterized by the onset of weight loss.”

What the sources say

• ?Not checked — no full text of the sourcecites [96] Berchane, 2007, Effect of mean diameter and polydispersity of PLG microspheres on drug release: Experiment and theory, Int. J. Pharm. source

In the paper

“Several studies suggest that nanoparticles of any material may create specific biodistribution and toxicological profiles [95].”

What the sources say

• ?Not checked — no full text of the sourcecites [95] Olivier, 1999, Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity, Pharm. Res. source

In the paper

“Furthermore, multiple studies demonstrate that PLGA can easily be formulated into the drug carrying devices at all scales, i.e., as nanospheres, as microspheres and even as millimeter sized implants, can encapsulate a wide range of drugs, peptides or proteins and can be delivered over different periods of time with diverse routes of delivery.”