Class Of Biodegradable Polymers Research Articles

Insight on relationship between crystallinity and band gap energies of polyhydroxyalkanoates polymers

This study explores the electronic properties of polyhydroxyalkanoates (PHAs), a class of biodegradable polymers. The focus lies in examining the relationship between crystallinity and band gap energies in PHAs. A notable discovery is the identification of a band gap plateau, suggesting a threshold in electronic properties with increasing polymer chain length. DFT calculations were employed to model the complexities of PHA polymers, with the conductor-like polarizable continuum model (CPCM) offering insights into solvent effects. The results demonstrate a strong negative correlation between crystallinity and band gap in both vacuum and CPCM environments. This study underscores the significance of structural order in shaping the electronic properties of PHAs, paving the way for the development of sustainable polymeric materials for various applications.

Biopolymers: Anindispensableentity for mankind

Polymers have become essential part of life. One can’t think of life without polymers, reason being their innumerable physical and engineering characteristics. Most prominent quality of polymers is their low cost and durability.However, seize to strength ratio of polymers is large as compared to metals. Heat capacity of polymers is also less. Structural strength of polymers is also poor which make them unsuitable for heavy structures. Above all polymer are non biodegradables they may persist in environment for centuries. Due to this disability many countries have imposed restrictions on their use. Low price, long life and readiness to adopt any shape has made polymers invulnerable. Non bio degradability of synthetic polymers shifted the quilt towards the invention of biopolymers. Scientists found the solution in biopolymers. They can be biosynthesized by living organisms or chemically synthesized from biological matter. The biopolymers are natural polymers formed by living organisms. Biopolymers are monomeric units which are bound covalently to form large molecules. Unlike polymers the biopolymers are biodegradable which decompose in bio-products with time after the expiry of intended purpose. Mainly there are three classes of biodegradable polymers namely polysaccharides, polypeptides and poly nucleotides Biopolymers mostly find applications in manufacturing, packaging, biomedical engineering and food industry. Difference between natural and synthetic polymers is discussed. Advantages of biopolymers over polymers are compared. Present study enlists brief overview of biopolymers. Keywords: Polymers, Biopolymers, Biodegradable Abbreviations: PVC, PVDF, Tg, DNA, RNA

Synthesis and characterization of polyphosphoester/polyethylene glycol composite hydrogels

<p indent=0mm>The hydrogel, which has a three-dimensional (3D) cross-linked hydrophilic network structure, is widely used as biomedical scaffold for local drug delivery and tissue engineering. Especially, with the continuous development of 3D printing technology, hydrogel scaffolds are increasingly used in the field of regenerative medicine. Polyphosphoester is a class of biodegradable polymers with repeated phosphoester linkages in the backbone, and a series of polyphosphoester materials have been synthesized for biomedical applications. For instance, a variety of amphiphilic polyphosphoester-based copolymers have been synthesized by Wang’s group, and used as the nanocarriers of hydrophobic anticancer drugs as well as siRNA. In addition, Yan’s group has prepared hyper-branched polyphosphoester as the drug delivery systems of hydrophobic anticancer drugs and photodynamic agents. Recently, Wooley and co-workers have synthesize the amphiphilic co-polymer of poly(ethylene oxide) and polyphosphoester, and used to encapsulated paclitaxel (PTX) with high contents for cancer therapy. And, they also conjugated the PTX into the side chain of polyphosphoester with pH-labile linkages for efficient tumor treatments. As the tissue engineering scaffold, polyphosphoester-based scaffolds were first used for fabrication of nerve guide conduits. And then, Elisseeff and co-workers have found the great potentials of phosphate-containing hydrogel for bone tissue engineering. In addition, Leong et al. found that the photocrosslinkable polyphosphoester hydrogel exhibited good compatibility and potentially osteoinductive ability for goat bone marrow-derived mesenchymal stem cells. Therefore, polyphosphoester hydrogel could be a promising scaffold for bone tissue engineering. In this study, water-soluble macromers polyphosphate diacrylate (PEEP-DA) and polyethylene glycol diacrylate (PEG-DA) were first synthesized, and characterized by ¹H NMR. And then, the PEEP/PEG composite hydrogels at various polyphosphoester contents were controlled by varying the feed ratio of the macromers PEEP-DA and PEG-DA (1:29, 2:28, and 5:25), and the PEEP/PEG hydrogels were fabricated by exposing aqueous solutions of these macromers with photoinitiator to UV light irradiation. We systematically studied the structure, biodegradability, biocompatibility, and bone differentiation of the hydrogel scaffold. Compared with PEG hydrogel, these PEEP/PEG hydrogels exhibited better biodegradability due to the degradation properties of polyphosphoester. And, the PEEP/PEG composite hydrogels, which was prepared at PEEP-DA/PEG-DA mass ratio of 5:25, disappeared almost completely after post implantation into mice for 28 d. After encapsulating bone marrow mesenchymal stem cells (BMSCs) during the preparation process, the cell viabilities in the composite PEEP/PEG hydrogels were better than that in the control PEG hydrogel. In addition, the alkaline phosphatase activity, a key maker of early osteogenic differentiation, was evaluated after co-incubation for 7 or 14 d. It could be found that the alkaline phosphatase activity in the PEEP/PEG composite hydrogels, either for 7 or <sc>14 d,</sc> was significantly higher than that of the control PEG hydrogel. The differentiation process of BMSCs into bone is usually accompanied by the calcium deposition. The polyphosphoester has shown osteoinductivity according to previous reports. We found that the amount of calcium deposition was significantly higher in the PEEP/PEG composite hydrogels than that in the PEG hydrogel, especially after co-incubation for <sc>21 d,</sc> which is well consistent with the result of other groups. Collectively, this study reported a new PEEP/PEG composite hydrogels, which exhibited the potential as tissue engineering scaffolds.

Neutral, water-soluble poly(ester amide) hydrogels for cell encapsulation

Hydrogels are of significant interest for cell encapsulation and delivery in regenerative medicine. Poly(ester amide)s (PEAs) are a class of biodegradable polymers that exhibit promise for biomedical applications due to the degradability of the ester and amide linkages in their backbones, their preparation from biomolecules such as amino acids, and the ability to readily tune their properties through a modular synthesis approach. Water-soluble PEAs containing cationic arginine moieties have previously been developed, but to the best of our knowledge, neutral water-soluble PEAs based on non-charged amino acids have not been reported. Using a poly(ethylene glycol) (PEG)-based macromonomer, we describe here the syntheses of water-soluble amino acid-containing PEAs containing crosslinkable alkenes in their backbones. These PEAs were converted into hydrogels through photoinitiated crosslinking and their properties were compared, including gel content, water content, swelling, and Young’s moduli. Subsequent cell culture studies on a subset of hydrogels confirmed that human adipose-derived stromal cells (ASCs) showed > 75% viability at 24 h post-encapsulation. To explore the potential of the hydrogels as cell delivery systems for applications in soft tissue regeneration, adipogenic differentiation of the encapsulated ASCs was probed in vitro at 7 days. Analysis of glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity and intracellular lipid accumulation indicated that the hydrogels provided a supportive environment for ASC adipogenesis. Overall, these PEAs provide a new platform that warrants further development for regenerative medicine applications.

Reducible Branched Ester-Amine Quadpolymers (rBEAQs) Codelivering Plasmid DNA and RNA Oligonucleotides Enable CRISPR/Cas9 Genome Editing.

Functional codelivery of plasmid DNA and RNA oligonucleotides in the same nanoparticle system is challenging due to differences in their physical properties as well as their intracellular locations of function. In this study, we synthesized a series of reducible branched ester-amine quadpolymers (rBEAQs) and investigated their ability to coencapsulate and deliver DNA plasmids and RNA oligos. The rBEAQs are designed to leverage polymer branching, reducibility, and hydrophobicity to successfully cocomplex DNA and RNA in nanoparticles at low polymer to nucleic acid w/w ratios and enable high delivery efficiency. We validate the synthesis of this new class of biodegradable polymers, characterize the self-assembled nanoparticles that these polymers form with diverse nucleic acids, and demonstrate that the nanoparticles enable safe, effective, and efficient DNA-siRNA codelivery as well as nonviral CRISPR-mediated gene editing utilizing Cas9 DNA and sgRNA codelivery.

Biodegradable galactitol based crosslinked polyesters for controlled release and bone tissue engineering

Various classes of biodegradable polymers have been explored towards finding alternates for the existing treatments for bone disorders. In this framework, two families of polyesters using an array of crosslinkers were synthesized. One was based on galactiol/adipic acid and the other based on galactitol/dodecanedioic acid. The structures of the polymers were confirmed by FTIR and further confirmed by 1H NMR. DSC showed that the polymers were amorphous and the glass transition temperature increased with increase in crosslinking. DMA and contact angle analysis revealed that the modulus and hydrophobicity increased with increase in crosslinking. Swelling studies demonstrated that %swelling decreased with increase in crosslinking. The in vitro hydrolytic degradation studies and dye release studies of all the polymers exhibited that the degradation and release rate decreased with increase in crosslinking, hydrophobicity and modulus. Degradation and release followed first order kinetics and Higuchi kinetics, respectively. The preliminary in vitro cytotoxicity studies proved that this array of polymers was not cytotoxic. Osteogenic differentiation of pre-osteoblasts was observed in three dimensional (3D) porous scaffolds prepared using these polymers. This study demonstrates the ability to modulate the physical properties, degradation and release kinetics of these biodegradable polymers through smart selection of crosslinkers. The findings of these studies have important implications for developing novel biodegradable polymers for drug delivery and tissue engineering applications.

Perspective highlights on biodegradable polymeric nanosystems for targeted therapy of solid tumors.

Introduction: Polymeric nanoparticles (NPs) formulated using biodegradable polymers offer great potential for development of de novo drug delivery systems (DDSs) capable of delivering a wide range of bioactive agents. They can be engineered as advanced multifunctional nanosystems (NSs) for simultaneous imaging and therapy known as theranostics or diapeutics. Methods: A brief prospective is provided on biomedical importance and applications of biodegradable polymeric NSs through reviewing the recently published literature. Results: Biodegradable polymeric NPs present unique characteristics, including: nanoscaled structures, high encapsulation capacity, biocompatibility with non-thrombogenic and non-immunogenic properties, and controlled-/sustained-release profile for lipophilic and hydrophilic drugs. Once administered in vivo, all classes of biodegradable polymers (i.e., synthetic, semi-synthetic, and natural polymers) are subjected to enzymatic degradation; and hence, transformation into byproducts that can be simply eliminated from the human body. Natural and semi-synthetic polymers have been shown to be highly stable, much safer, and offer a non-/less-toxic means for specific delivery of cargo drugs in comparison with synthetic polymers. Despite being biocompatible and enzymatically-degradable, there are some drawbacks associated with these polymers such as batch to batch variation, high production cost, structural complexity, lower bioadhesive potential, uncontrolled rate of hydration, and possibility of microbial spoilage. These pitfalls have bolded the importance of synthetic counterparts despite their somewhat toxicity. Conclusion: Taken all, to minimize the inadvertent effects of these polymers and to engineer much safer NSs, it is necessary to devise biopolymers with desirable chemical and biochemical modification(s) and polyelectrolyte complex formation to improve their drug delivery capacity in vivo.

Poly(beta-amino ester)-poly(ethylene glycol) micelles for intracellular therapeutic drug delivery

Event Abstract Back to Event Poly(beta-amino ester)-poly(ethylene glycol) micelles for intracellular therapeutic drug delivery James G. Shamul1, Yechan Kang1, Jayoung Kim1 and Jordan J. Green1, 2 1 Johns Hopkins University, Biomedical Engineering, United States 2 Johns Hopkins University and Medicine, Ophthalmology, Oncology, Neurosurgery, and Materials Science and Engineering, United States Introduction: Self-assembled micellar structures have been extensively studied as drug carriers for cancer and other diseases. These micelles, which are generally formulated with amphiphilic block copolymer, allow controlled release of encapsulated drugs[1]. Poly(β-amino ester) (PBAE) is a class of biodegradable polymers that is widely investigated as non-viral vectors for gene and drug delivery[2]. Neutrally charged, hydrophilic poly(ethylene glycol) (PEG) molecules can be coated onto a positive surface of nanoparticles to prevent aggregation and clearance from non-specific adsorption of proteins on the surface[3]. In this study, PEG was end-capped to hydrophobic PBAE polymer to provide amphiphilicity, trigger micellar self-assembly in aqueous solution, and promoted particle stability. Materials and Methods: To synthesize PEG-PBAE, acrylate-terminated hydrophobic PBAE was reacted with PEG molecules to produce PEG-PBAE-PEG amphiphilic copolymers. Gel permeation chromatography and 1H NMR analysis verified successful PEG end-capping. After micellar self-assembly in aqueous solution, the micelles were characterized by measuring the surface charge by dynamic light scattering, size by nanoparticle tracking analysis, and critical micelle concentration (CMC) by pyrene fluorescence. Micellar morphology and aggregation were visualized by TEM. The cellular uptake and cytotoxicity of doxorubicin (dox)-loaded micelles and blank micelles were evaluated in HUH7 human hepatocellular carcinoma cells using comparable free dox concentration for comparison. Results: PEG-PBAE copolymer was determined to have a CMC of .0155mg/mL. Nanosight data suggests micelle stability due to consistent size in water, PBS, 25%, 50%, and 75% v/v FBS-PBS over 24 h with hydrodynamic diameter of approximately 220 nm. Zeta potential of blank micelles was near neutral at -1.88 mV. Loading efficiency of doxorubicin in PEG-PBAE micelles was determined to be 2.1% by mass. Micelles exhibited 80% cellular uptake in Huh7 cells. Approximately 75% of the cells were killed when exposed to dox-loaded micelles or equivalent concentration of free dox. Conclusions: These results indicate that doxorubicin-loaded micelles can be formulated with a novel PEG-PBAE copolymer. PEG-PBAE micelles are stable over time and can successfully deliver drug cargo inside cancer cells and cause mortality The authors acknowledge Samsung Scholarship and NIH 1R01EB016721 for funding, Johns Hopkins Microscope Facility core for TEM, and Wilmer Core Grant (P30-EY001865, Imaging and Microscopy Core Module) for flow cytometry.

Bioreducible hyperbranched polyglycerols with disulfide linkages: Synthesis and biocompatibility evaluation

ABSTRACTIn this article, we describe the development of multifunctional, water‐soluble hyperbranched polyglycerols containing redox‐sensitive disulfide linkages as a new class of biodegradable polymers. The polymers were synthesized by the anionic ring opening multibranching (co)polymerization of glycidol with an epoxide monomer bearing disulfide groups, 2‐((2‐oxiran‐2‐ylmethoxy)ethyl)disulfanyl) ethan‐1‐ol. Polymerizations were optimized at 65 °C unlike the homopolymerization of glycidol. Both low (5–10 kDa) and high (100 kDa) molecular weight polymers were synthesized in a controlled manner with low polydispersity. The polymers underwent degradation in presence of reducing agents such as tris(2‐carboxyethyl)phosphine, dithiothreitol, and glutathione resulting in low molecular weight fragments with thiol groups. Blood compatibility analysis using coagulation, platelet activation, complement activation and red blood cell lysis assays as well as cell toxicity analysis using MTS assay revealed the excellent biocompatibility of these newly synthesized polymer architectures. All these features make these polymers suitable for intracellular delivery of therapeutic molecules. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2104–2115

USE OF BIODEGRADABLE MICRO AND NANO-PARTICLES IN VACCINE DELIVERY

Effective immunizations in recent years become most important in terms of new antigens, adjuvants and routes of vaccination. Vaccination by oral route remains the preferred route for both patients and practitioners. To improve the bioavailability of peptides, proteins and antigens, they are associated with colloidal carrier e.g. polymeric nanoparticles. Synthetic polymers are choosen for longer duration of drug release, but they are limited by the use of organic solvents and relatively harsher formulation conditions. Amongst the different classes of biodegradable polymers, the thermoplastic aliphatic poly (esters) like poly (lactide) (PLA), poly (glycolide) (PGA), and especially the copolymer of lactide and glycolide, poly (lactide-co-glycolide) (PLGA) have generated immense interest due to their favorable properties such as good biocompatibility, biodegradability, and mechanical strength. Also, they are easy to formulate into different devices for carrying a variety of drug classes such as vaccines, peptides, proteins, and micromolecules. Also, they have been approved by the Food and Drug Administration (FDA) for drug delivery. In this mini-review, various formulation aspects of these biodegradable polymers, in the micro and nano range, were discussed.

Depot Based Drug Delivery System for the Management of Depression

Depression is a common mental disorder discerns with depressed mood, loss of interest, the primary treatment methods are drug therapy, electroconvulsive therapy, psychotherapy, light therapy, vagus nerve stimulation, etc. A number of innovative delivery systems have been developed to address suboptimal therapy outcomes by enhancing drug delivery, assuring efficacy of treatment, reducing side effects, improving compliance and drug targeting specific locations resulting in a higher efficiency. Depot delivery offers the advantage of a very high loading, controlled release of drug for an extended period of time and reduces frequency of dosing. The increase in AUC and decrease in Cmax reflects that the depot formulations could reduce the toxic complications and limitations of conventional and oral therapies. Products at preclinical and clinical stages include formulations of naltrexone and buprenorphine for alcoholism/drug abuse, GLP-1 peptides for diabetes, r-hFSH for fertility, dopamine for nerve growth, dexamethasone for ocular treatment, melanotan for cancer prevention, plasmid DNA for cancer prevention, a variety of vaccines, octreotide generics, etc. Most depot formulations are comprised of biodegradable polymer-excipients that control the rate of drug release and resorbs during/after drug release. The major advantage of depot antipsychotics over oral medication was facilitation of compliance in medication taking. One class of biodegradable polymers that has gained wide acceptance and still attractive today is lactide/glycolide polymers. The greatest advantage of these degradable polymers is that they are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways. This versatile delivery system offers the advantage of a very high loading and controlled release of various drug for an extended period of time compared with plain delivery system. New formulations of depression can offer advantages over older formulations in terms of convenience, side effect profiles, efficacy, and/or a fast onset of action.

Biodegradable Polymers

Biodegradable materials are used in packaging, agriculture, medicine and other areas. In recent years there has been an increase in interest in biodegradable polymers. Two classes of biodegradable polymers can be distinguished: synthetic or natural polymers. There are polymers produced from feedstocks derived either from petroleum resources (non renewable resources) or from biological resources (renewable resources). In general natural polymers offer fewer advantages than synthetic polymers. The following review presents an overview of the different biodegradable polymers that are currently being used and their properties, as well as new developments in their synthesis and applications.

Dynamic polythioesters via ring-opening polymerization of 1,4-thiazine-2,5-diones

We describe the preparation and characterization of polythioesters composed of alternating alpha-amino acid and alpha-thioglycolic acid residues that undergo dynamic constitutional exchange under mild conditions. The polymers are assembled via reversible ring-opening polymerizations of 1,4-thiazine-2,5-diones and related monomers in solution-phase conditions that do not require the use of transition metal catalysts. Because 1,4-thiazine-2,5-diones can be derived in part from alpha-amino acids, a variety of side chain functionalized monomers in optically pure forms could readily be accessed. In addition, the resulting polythioesters have the potential for intra- and inter-chain hydrogen bonding, which is known to impart materials properties to other previously studied polyamides. The studies reported here could be useful in advancing a new class of biodegradable polymers and furthermore suggest that dynamic constitutional exchange could be exploited to modify many known synthetic and natural polythioesters.

The synthesis of cationic polyurethanes to study the effect of amines and structures on their DNA transfection potential

Polyurethanes (PUs) are a class of biodegradable polymers that have been applied as tissue-engineering materials with minimum toxicity. In our study, a new series of cationic PUs containing tertiary amines in the backbone and primary, secondary and tertiary amines in the side chains (PU1, PU2 and PU3, respectively) was synthesized and used as nonviral vectors for gene delivery. In addition, we introduced glycidol into the structure of PU for greater solubility and biocompatibility and grafted various amines in the side chains (PUg1, PUg2, PUg3). The structural characteristics of PUs and the physicochemical properties of their formed complexes with DNA were determined and correlated with their transfection efficiency. The results reveal that PU1, PU3, PUg1 and PUg3 could bind with DNA and yielded positively charged complexes with a condensed size required for transfection. These PUs are considered to be noncytotoxic (hundred times less) compared to polyethylenimine (PEI) or poly(2-dimethylaminoethyl methacrylate), (PDMAEMA). The hydrolytical degradation studies indicate that PU-glycidyl systems (PUg1 and PUg3) can be degraded in 20 mM HEPES buffer at pH 7.4 in approximately 8 h but that PU1 and PU3 lasted much longer. PUg1 and PUg3 are the best amongst cationic PUs to transfect DNA into COS-7 cells with an efficacy comparable to the well-known gene carrier PDMAEMA. In addition, PUg1 and PUg3 possess greater biocompatibility and biodegradability. A new way to prepare cationic polymers without cytotoxicity but with highly transfecting activity could be very helpful to the in vivo gene transfection where large amounts of cationic polymers are required.

Drying biodegradable poly(hydroxybutyrate‐co‐3‐hydroxyvalerate) gels in the elongated state to improve their mechanical properties

AbstractPolyhydroxyalkanoates are a class of biodegradable polymers that may be used more as environmentally friendly materials if their mechanical properties can be improved. We approached this goal by modifying poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) with a well‐established processing technique involving crosslinking the polymer chains and then drying a swollen gel of the network under uniaxial strain. The mechanical properties of the resulting oriented films were determined in continuous extension as a function of the degree of crosslinking and the extent of strain during the drying process. Crosslinking invariably improved the toughness. Similarly, the subsequent orientation of the process generally increased the toughness as well, but in some cases, a reduction in the extensibility offset the increase in the ultimate stress at break and yielded reduced values of the toughness. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 95: 1519–1523, 2005

Oxidized cellulose esters: I. Preparation and characterization of oxidized cellulose acetates — a new class of biodegradable polymers

Oxidized cellulose acetates (OCA), with a degree of substitution (DS) value ranging between 1.1 and 2.3 and a free carboxylic acid group content of 20% (w/w), have been prepared by reacting oxidized cellulose (OC, COOH content 20% w/w) with a mixture of acetic acid and acetic anhydride in the presence of sulfuric acid as a catalyst. The DS of OCA, in general, increased with increasing reaction temperature, reaction time, and concentration of acetic anhydride in the reaction mixture. The yield of OCA, in contrast, increased with increasing concentration of acetic anhydride and decreased with increasing reaction time and temperature. The intrinsic viscosity of OCA varied between 0.100 and 0.275, depending on the reaction conditions used during its preparation. In general, an increase in reaction temperature and the use of a prolonged reaction time decreased the intrinsic viscosity of OCA. No correlation was found between DS and intrinsic viscosity of OCA. The apparent pKa of OCA is 3.7-3.9. The new OCA polymers are practically insoluble in water and slowly dissolve in pH 7.4 phosphate buffer solution. They are, however, soluble in a range of organic solvents (e.g. ethyl acetate, acetone, acetone/water, chloroform/methylene chloride, dimethylsulfoxide, dimethylformamide, and/or chloroform/methanol).

The manufacturing techniques of various drug loaded biodegradable poly(lactide- co-glycolide) (PLGA) devices

A considerable research has been conducted on drug delivery by biodegradable polymeric devices, following the entry of bioresorbable surgical sutures in the market about two decades ago. Amongst the different classes of biodegradable polymers, the thermoplastic aliphatic poly(esters) like poly(lactide) (PLA), poly(glycolide) (PGA), and especially the copolymer of lactide and glycolide, poly(lactide-co-glycolide) (PLGA) have generated immense interest due to their favorable properties such as good biocompatibility, biodegradability, and mechanical strength. Also, they are easy to formulate into different devices for carrying a variety of drug classes such as vaccines, peptides, proteins, and micromolecules. Also, they have been approved by the Food and Drug Administration (FDA) for drug delivery. This review discusses the various traditional and novel techniques (such as in situ microencapsulation) of preparing various drug loaded PLGA devices, with emphasis on preparing microparticles. Also, certain issues about other related biodegradable polyesters are discussed.

Chemical changes during in vivo degradation of poly(anhydride-imide) matrices

The in vivo degradation characteristics of a novel class of biodegradable polymers, poly(anhydride–imides), were investigated. The poly(anhydride–imides) examined were poly[trimellitylimidoglycine- co-1,6-bis( p-carboxyphenoxy)hexane] (TMA-gly : CPH) in 10 : 90, 30 : 70 and 50 : 50 molar ratios and poly[pyromellitylimidoalanine- co-1,6-bis( p-carboxyphenoxy)hexane] (PMA-ala : CPH) in 10 : 90 and 30 : 70 molar ratios. The polymer matrices were compression-molded into circular discs, then implanted in rat subcutaneous tissues for nearly two months. At defined time intervals, the animals were sacrificed and explants analyzed. Proton NMR spectroscopic analysis revealed a complete absence of imide monomer units in PMA-ala : CPH compositions after 28 d and complete removal of imide units at 56 d from TMA-gly matrices. Gross observation of the implants closely correlated to the imide content: with decreasing imide content, the explants darkened and fragmented at a faster rate. The chemical compositions of the poly(anhydride– imide) explants were also monitored using IR spectroscopy. The residual amount of anhydride bonds in the polymer backbone following implantation were calculated from peaks specific to the anhydride bonds relative to the total amount of carbonyl bonds present. Initially, the imide (TMA-gly or PMA-ala) anhydride bonds were rapidly hydrolyzed then solubilized, followed by the slower hydrolysis of the CPH monomer anhydride bonds.

Biodegradable comb polyesters: Part 1 synthesis, characterization and structural analysis of poly(lactide) and poly(lactide-coglycolide) grafted onto water-soluble poly(vinyl alcohol) as backbone

To overcome discontinuous or polyphasic drug release rates of parenteral delivery systems (PDSs) for peptides and proteins, typical for linear polyesters, novel biodegradable brush-like poly(lactide) and poly(lactide-co-glycolide) (PLG) grafted onto water-soluble poly(vinyl alcohol) (PVA) as backbone were investigated. These polymers were synthesized by ring-opening melt polymerization using stannous octoate as catalyst. The branched PVA-PLGs were characterized by 1D- and 2D-n.m.r. spectroscopy and other methods, such as i.r., g.p.c., d.s.c. and static light scattering. The incorporation of the backbone and the comb structure was demonstrated by 1H- and 13C - n.m.r. spectra, as well as by light scattering studies. The physico-chemical properties, such as molecular composition and architecture, molecular weight, degree of crystallinity, melting point and glass transition point, could be systematically adjusted to the requirements of drug delivery. Therefore, this new class of biodegradable polymers has considerable potential as a PDS.

Controlled Drug Delivery by Biodegradable Poly(Ester) Devices: Different Preparative Approaches

There has been extensive research on drug delivery by biodegradable polymeric devices since bioresorbable surgical sutures entered the market two decades ago. Among the different classes of biodegradable polymers, the thermoplastic aliphatic poly (esters) such as poly(lactide) (PLA), poly(glycolide) (PGA), and especially the copolymer oflactide and glycolide referred to as poly(lactide-co-glycolide) (PLGA) have generated tremendous interest because of their excellent biocompatibility, biodegradability, and mechanical strength. They are easy to formulate into various devices for carrying a variety of drug classes such as vaccines, peptides, proteins, and micromolecules. Most importantly, they have been approved by the United States Food and Drug Administration (FDA) for drug delivery. This review presents different preparation techniques of various drug-loaded PLGA devices, with special emphasis on preparing microparticles. Certain issues about other related biodegradable polyesters are discussed.