Novel Poly (glycerol-adipate) Polymers Used for Nanoparticle Making: A Study of Surface Free Energy

Abstract Nanoparticles made of biodegradable polymers has become the best approach for nanoparticle making due to their compatibility with the human body. New glycerol adipate polymers with hydroxyl group substituted with different percent of acyl group, sited as figures within the abbreviated name in the text, and triptophan were synthesized and proposed to be used in the preparction of dexamethason phosphate loaded nanoparticles, using the evaporation-deposition technique. The particle forming ability, size and distribution of the nanoparticles might be related to more important physicochemical characteristics, such as the surface properties of the polymers. In this study surface free energies of five derivatives (0%, 20%, 40%, 100% and triptophan 5%) were determined by means of contact angle measurement carried out on films formed on the glass slides KSC Cam 100 instrument. The results were then incorporated into the Fowkes equation, toobtion the surface energy of the polymers. Also, different concentrations of methanol were used to obtion contact angles, which in turn were used to give the critical surface tension (γ c ) of the polymers, using the Zizman's method. The results of surface characteristics indicated that the 40% C 8 polymer was probably the most consistent, compared to the others during the preparation stage, in order to form smaller sized particles with a narrower distribution, correlating with the other works carried out on the loaded particles. In conclusion, it seems that this method could be used to predict characteristics of polymers used for the selection of the best polymer in this series and probably other polymers for nanoparticle making, particularly for the loading of ionized drugs

Cholesterol level affects surface charge of lipid membranes in saline solution

Peer reviewe

New N-acyl amino acid-functionalized biodegradable polyesters for pharmaceutical and biomedical applications

A novel class of biodegradable Polyesters has been generated by coupling Poly(glycerol adipate) with N-acyl aromatic amino acids. This new set of polymers from this highly versatile polymeric platform may offer unprecedented new opportunities to produce biodegradable and biocompatible polymers with tailorable physical-chemical properties

Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies

PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Properties of acyl modified poly(glycerol-adipate) comb-like polymers and their self-assembly into nanoparticles

There is an increasing need to develop bio-compatible polymers with an increased range of different physicochemical properties. Poly(glycerol-adipate) (PGA) is a biocompatible, biodegradable amphiphilic polyester routinely produced from divinyl adipate and unprotected glycerol by an enzymatic route, bearing a hydroxyl group that can be further functionalized. Polymers with an average Mn of ∼13 kDa can be synthesized without any post-polymerization deprotection reactions. Acylated polymers with fatty acid chain length of C4, C8, and C18 (PGAB, PGAO, and PGAS, respectively) at different degrees of substitution were prepared. These modifications yield comb-like polymers that modulate the amphiphilic characteristics of PGA. This novel class of biocompatible polymers has been characterized through various techniques such as FT-IR, 1H NMR, surface, thermal analysis, and their ability to self-assemble into colloidal structures was evaluated by using DLS. The highly tunable properties of PGA reported herein demonstrate a biodegradable polymer platform, ideal for engineering solid dispersions, nanoemulsions, or nanoparticles for healthcare applications

Coencapsulation of Arsenic- and Platinum-based Drugs for Targeted Cancer Treatment

No AbstractPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64451/1/ange_200903655_sm_miscellaneous_information.pd

Variation in structure and properties of poly(glycerol adipate) via control of chain branching during enzymatic synthesis

Poly (glycerol adipate) (PGA) can be produced from divinyl adipate and unprotected glycerol by an enzymatic route to generate a polymer with relatively low molar mass (12 kDa). PGA bears a pendant hydroxyl group which imparts a hydrophilic character to this water insoluble polymer. We have examined the effect of synthesis temperature on polymer characteristics through various techniques including FT-IR, 1H and 13C NMR, surface and thermal analysis, both to expand the data already present in the literature about this material and to understand better its properties for potential pharmaceutical applications. The use of a lipase (Novozym 435) as a catalyst suppresses cross-linking at the pendant glyceryl hydroxyl through steric hindrance at the active site, thus producing polymers with low degrees of branching (5–30%), and removes the need for any pre- or post-polymerization protection/deprotection reactions. Careful temperature control during synthesis can give polymers with reproducible molecular weights and reduced amounts of polymer branching compared to synthesis at higher temperatures. Due to the ability of the synthetic route to produce a range of structures, PGA generated by enzymatic routes may emerge as a useful biodegradable polymer platform to engineer solid dispersions or nanoparticles for healthcare applications

Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers.

In this study, Taguchi design was used to determine optimal parameters for the preparation of bovine serum albumin (BSA)-loaded nanoparticles (NPs) using a biodegradable polymer poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL). NPs were prepared, using BSA as a model protein, by the double emulsion evaporation process followed by spray-drying from leucine to form nanocomposite microparticles (NCMPs). The effect of various parameters on NP size and BSA loading were investigated and dendritic cell (DC) uptake and toxicity. NCMPs were examined for their morphology, yield, aerosolisation, in vitro release behaviour and BSA structure. NP size was mainly affected by the polymer mass used and a small particle size ≤500 nm was achieved. High BSA (43.67 ± 2.3 μg/mg) loading was influenced by BSA concentration. The spray-drying process produced NCMPs (50% yield) with a porous corrugated surface, aerodynamic diameter 1.46 ± 141 μm, fine particle dose 45.0 ± 4.7 μg and fine particle fraction 78.57 ± 0.1%, and a cumulative BSA release of 38.77 ± 3.0% after 48 h. The primary and secondary structures were maintained as shown by sodium dodecyl sulphate poly (acrylamide) gel electrophoresis and circular dichroism. Effective uptake of NPs was seen in DCs with >85% cell viability at 5 mg/mL concentration after 4 h. These results indicate the optimal process parameters for the preparation of protein-loaded PGA-co-PDL NCMPs suitable for inhalation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci

New FTY720-docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia and inhibits metastatic breast tumour growth

Purpose: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity. Methods: Docetaxel, FTY and glucosamine were covalently conjugated to poly(lactic-co-glycolic acid) (PLGA). NPs were characterised by dynamic light scattering and electron microscopy. The cellular uptake, cytotoxicity and in vivo antitumor efficacy of CNPs were evaluated. Results: We show for the first time that in triple negative breast cancer cells FTY provides chemosensitisation to DTX, allowing a four-fold reduction in the effective dose. We have encapsulated both drugs in PLGA complex NPs (CNPs), with narrow size distribution of ~ 100 nm and excellent cancer cell uptake providing sequential, sustained release of FTY and DTX. In triple negative breast cancer cells and mouse breast cancer models, CNPs had similar efficacy to systemic free therapies, but allowed an effective drug dose reduction. Application of CNPs has significantly reversed chemotherapy side effects such as weight loss, liver toxicity and, most notably, lymphopenia. Conclusions: We show for the first time the DTX chemosensitising effects of FTY in triple negative breast cancer. We further demonstrate that encapsulation of free drugs in CNPs can improve targeting, provide low off-target toxicity and most importantly reduce FTY-induced lymphopenia, offering potential therapeutic use of FTY in clinical cancer treatment