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Ukicrs poster 2015


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In-vitro degradation of polymeric carriers of PLGA, PGA-co-PDL polymers

Published in: Health & Medicine
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Ukicrs poster 2015

  1. 1. 1. Brannon - Peppas L (1997). Med Plast Biomater 4: 34-44; 2. Nitesh K. Kunda & Iman M. A lfagih, Sarah R. Dennison, H M. Tawfeek, S Somavarapu, G A. Hutcheon & I Y. Saleem. (2014). Pharmaceutical research , 1-13. 3. Thompson C. J., D. Hansford, S. Higgins, C. Rostron, G. A. Hutcheon and D. L. (2009) Munday. Journal of Microencapsulation. 26(8): 676–683; 4. Tawfeek H. M., S.H. Khidr, E.M Samy, S.M Ahmed, M Murphy, A. Mohammed, A. Shabir, G. Hutcheon & I. Saleem.(2011). Pharmaceutical research, 28(9), 2086-2097; 5. C. Pinto Reis et al. Nanomedicine: nanotechnology, biology, and medicine. 2:8-21 (2006). References N. M. Osman1,2, K. Sin1, J. Jaffer1, K. Ritchie1, I. Y. Saleem1, G. A. Hutcheon1, 1 School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK 2 Forensic Medicine & Clinical Toxicology Dep., Sohag University, Sohag, Egypt Introduction Formulation & Drug Delivery Research DEGRADATION OF PLGA AND PGA-co-PDL POLYMERIC CARRIERS IN SIMULATED LUNG FLUID FOR PULMONARY DRUG DELIVERY Results and Discussion Conclusions and Future work Aggregation of PGA-co-PDL NPs made it difficult to determine any size reduction due to degradation. PLGA NPs reduced in size indicating some degradation occurred under the stated experimental conditions. PGA-co-PDL NPs produced a less acidic environment compared with PLGA NPs hence less inflammation may occur in vivo. Determination of changes in polymer molecular weight by GPC analysis and observation of the particles using Transmission Electron Microscopy are currently in progress which will increase our understanding of the stability and degradation of these particles. Acknowledgements Nashwa Osman would like to thank the Egyptian Educational and Cultural Bureau for funding this project and thank LJMU staff and technicians for their kind support. Successful drug delivery systems are able to deliver an active therapeutic agent to a specific targeted site in the duration of time with minimal side effects1. Aliphatic polyesters are widely used for drug delivery applications, the most common being poly (lactic-co-glycolic acid), PLGA . The main drawbacks of using PLGA are the initial burst release and the bulk degradation that produces acidic products resulting in a reduction in pH at the site of drug action. A novel aliphatic polyester, poly (glycerol adipate-co-w- pentadecalactone), (PGA-co-PDL), synthesized from the lipase catalysed poly-condensation and ring-opening polymerization reaction with the potential to overcome these drawbacks has recently been investigated2,3. These aliphatic polyesters achieve the controlled-release of drugs by bulk degradation which leads to uniform disintegration of the drug delivery system with a decrease in molecular weight (MWt) and size until complete dissolution. The degradation products consist of the parent alcohol and acid monomeric units which can create an acidic environment depending on their chemistry. In vivo these products then enter Kreb’s cycle to decompose to CO2 and H2O. Rate-control of drug release can by achieved by controlling the degradation rate of polymer chemistry; monomeric ratio, MWt and hydrophobicity, particle characters; size, core, coating or matrix thickness and its formulation, and with the target physicochemical environment. Aim The aim of this study was to evaluate the stability and degradation of polymeric nanoparticles (NPs) prepared from PLGA and PGA-co-PDL under in-vitro simulated pulmonary physiologic conditions as a suspension in simulated lung fluid (SLF) at 37 o C. Materials and Methods Acid terminated PLGA (50:50) with a MWt of 7000- 17000 KDa (Sigma Aldrich) and PGA-co-PDL (synthesized and characterized as previously reported by Thompson et al3) were used to prepare NPs by the single emulsion solvent evaporation method5 using poly vinyl alcohol as an emulsifier. NPs were centrifuged twice at 78,000g, and 4ºC for 40 min. Initial MWt of both polymers were analyzed using Gel Permeation Chromatography (GPC)3 (Viscoteck TDA Model 300 operating OmniSEC3 software) calibrated with polystyrene standards. PLGA and PGA-co-PDL NPs (10 mg) were stored at 37oC as a suspension in SLF (Gamble’s solution) at pH 7.4 with axial rotation of 15 rpm. At specified time points between 1-28 days the pH of the suspension was measured. NPs were characterized for size and zeta potential using Malvern Zetasizer ZS. The initial polymer MWt was 17.57 and 14.73 KDa for PLGA and PGA-co- PDL respectively. NPs were successfully formulated with a size of 157.9 ± 2.19 nm and 179.8 ± 3.91 nm for PLGA and PGA-co-PDL respectively. The zeta potentials of PLGA and PGA-co-PDL NPs were -8.9 ± 0.5 and -9.72 ± 1.0 mV. The initial pH of the NPs suspension was 8.7 and 7.46 for PGA-co- PDL and PLGA NPs respectively NP size: The size of the PGA-co-PDL NPs increased over time with a corresponding increase in polydispersity suggesting the particles were aggregating. The PLGA NP decreased in size over time confirming their degradation without aggregation (Fig 1). 0 50 100 150 200 250 300 350 400 450 D1 D2 D4 D7 D14 D21 D28 Sizeinnm Daily interval PGA-co-PDL PLGA Fig 1. Size changes over the study time interval of both polymeric NPs NP zeta potential: The zeta potential was initially negative. After day 4, the negativity of the PGA-co-PDL NPs increased where-as little change was observed with PLGA NPs over time (Fig 2). -30.0 -25.0 -20.0 -15.0 -10.0 -5.0 0.0 D1 D2 D4 D7 D14 D21 D28 ZetapotentialinmV Daily interval PGA-co-PDL PLGA Fig 2. Zeta potential changes over the study time interval of both polymeric NPs pH analysis : The pH changes observed (Fig 3) confirmed that as the NPs degraded, the solution containing the NPs became more acidic. PLGA NPs showed a greater change in acidity indicating that the degradation products were more acidic. In vivo this may cause localized acidity promoting an inflammatory response. 0 1 2 3 4 5 6 7 8 9 10 D1 D2 D4 D7 D14 D21 D28 pHvalue Daily interval PGA-co-PDL PLGA Fig 3. pH changes over the study time interval of both polymeric NPs