Characterization Of The Size, Shape, And Drug Encapsulation Efficiency Of Plga Microcapsules Produced Via Electrojetting For Anticancer Agent Delivery
Open Access
- Author:
- Fattahi, Pouria
- Graduate Program:
- Bioengineering
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- None
- Committee Members:
- Mohammad Reza Abidian, Thesis Advisor/Co-Advisor
- Keywords:
- BCNU
Drug delivery
PLGA
Mathematical modeling - Abstract:
- Despite significant progress in the development of new chemotherapeutic agents and drug delivery methods for brain tumors, malignant gliomas (high grade brain tumor) remains deadly with a median survival period of only about a year. The high dosage of chemotherapeutic agents required for penetration through the blood brain barrier during chemotherapy not only kills cancer cells but also damages healthy tissues and causes adverse side effects. Hence, a major unmet challenge in the treatment of malignant gliomas is the development of effective and targeted local delivery of chemotherapeutic agents at the cellular level. Drug-loaded biodegradable microcapsules with high drug encapsulation efficiency and controlled shape and size are attractive candidates for a more precise control of anticancer agent delivery at the tumor sites. Here, I report the results of a systematic study of the size, shape, and drug release profiles of Poly(lactic-co glycolic) (PLGA) microcapsules produced and loaded with the anticancer agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) using an electrojetting technique. I report production of BCNU-loaded PLGA microcapsules in the form of flattened microspheres, microspheres, and microfibers with significantly (1) higher drug encapsulation efficiency, (2) more tunable drug loading capacity, and (3) narrower size distribution than those generated using other encapsulation methods. To prepare BCNU-PLGA solutions with PLGA concentrations ranging from 1 to 10 wt%, BCNU/PLGA mixtures (5 to 25 wt% with respect to PLGA) dissolved in chloroform were electrojetted on gold substrates. I quantified the shape and size distribution of BCNU-loaded PLGA microcapsules as a function of the polymer concentration and flow rate used during electrojetting, and characterized drug release profiles for microcapsules of three different morphologies: flattened microspheres, microspheres, and microfibers. Flattened microspheres were produced from 1 and 2 wt% PLGA solutions, while microspheres and microfibers were formed as the PLGA concentration increased to 3-5 wt% and 10% wt%, respectively. I investigated the effect of flow rate (i.e. 0.25, 0.5 and 1 mLh-1) on the size and monodispersity of BCNU-loaded PLGA microcapsules. Microcapsules of 1 wt% PLGA, 4 wt% PLGA, and 10 wt% PLGA formed at a flow rate of Q= 0.25 mLh-1 had narrower size distributions (CV= 4.6%, CV= 4.5%, and CV= 4.8%, respectively). A commonly accepted definition of monodispersity is CV < 5%. I also measured drug release profiles and developed mathematical models to estimate the effective diffusion coefficient of BCNU in different PLGA microcapsules. The BCNU release profiles for all three microcapsule morphologies were found to be in good agreement with model predictions for drug release as a result of drug diffusion and degradation of PLGA microcapsules.