Muhammad Usman Minhas1, Orva Abdullah2,3, Muhammad Sohail4, Ikrima Khalid5, Sarfaraz Ahmad3, Kifayat Ullah Khan6, Syed Faisal Badshah3. 1. College of Pharmacy, University of Sargodha, Sargodha, Pakistan. 2. Hamdard Institute of Pharmaceutical Sciences, Hamdard University, Islamabad, Pakistan. 3. Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan. 4. Department of Pharmacy, COMSATS University, Abbottabad, Pakistan. 5. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, Pakistan. 6. Quaid-e-Azam College of Pharmacy, Sahiwal, Pakistan.
Abstract
OBJECTIVE: Purpose of the current study was to improve the oral effectiveness of 5-fluorouracil (5-FU) by developing novel controlled, combinatorial drug delivery system (nCDDS) for co-delivery of 5-FU and leucovorin calcium (LC) for colon targeting. SIGNIFICANCE: On the basis of results obtained, novel controlled, combinatorial drug delivery system could be an effective strategy for the colon targeting of 5-FU and LC. METHODS: Free radical polymerization method was tuned and used to fabricate this nCDDS. The nCDDS is synthesized in two steps, first synthesis of 5-FU/LC calcium loaded nanogels and second, pre-synthesized 5-FU and LC loaded nanogels were dispersed in pectin based polymerized matrix hard gel. The nanogels and nCDDS gels were characterized for network structure, thermal stability, and surface morphology. Swelling and in vitro release studies were carried out at different pH 1.2 and 7.4 both for naive nanogels and combined matrix gels. In vivo study of combinatorial gel was performed on rabbits by using HPLC method to estimate plasma drug concentration and pharmacokinetics parameters. RESULTS: Structure and thermal analysis confirmed the formation of stable polymeric network. SEM of nanogels and combinatorial gels showed that the spongy and rough edges particles and uniformly distributed in the combinatorial gel. The prepared nCDDS showed excellent water loving capacity and pH responsiveness. Combinatorial gel showed excellent characteristic for colonic delivery of drugs, which were confirmed by various in vitro and in vivo characterizations. Acute oral toxicity study of combinatorial gel confirmed the biocompatible and nontoxic characteristics of developed formulation. CONCLUSION: Conclusively, it can be found that nCDDS showed excellent properties regarding drug targeting in a controllable manner as compared to naive PEGylated nanogels.
OBJECTIVE: Purpose of the current study was to improve the oral effectiveness of 5-fluorouracil (5-FU) by developing novel controlled, combinatorial drug delivery system (nCDDS) for co-delivery of 5-FU and leucovorin calcium (LC) for colon targeting. SIGNIFICANCE: On the basis of results obtained, novel controlled, combinatorial drug delivery system could be an effective strategy for the colon targeting of 5-FU and LC. METHODS: Free radical polymerization method was tuned and used to fabricate this nCDDS. The nCDDS is synthesized in two steps, first synthesis of 5-FU/LC calcium loaded nanogels and second, pre-synthesized 5-FU and LC loaded nanogels were dispersed in pectin based polymerized matrix hard gel. The nanogels and nCDDS gels were characterized for network structure, thermal stability, and surface morphology. Swelling and in vitro release studies were carried out at different pH 1.2 and 7.4 both for naive nanogels and combined matrix gels. In vivo study of combinatorial gel was performed on rabbits by using HPLC method to estimate plasma drug concentration and pharmacokinetics parameters. RESULTS: Structure and thermal analysis confirmed the formation of stable polymeric network. SEM of nanogels and combinatorial gels showed that the spongy and rough edges particles and uniformly distributed in the combinatorial gel. The prepared nCDDS showed excellent water loving capacity and pH responsiveness. Combinatorial gel showed excellent characteristic for colonic delivery of drugs, which were confirmed by various in vitro and in vivo characterizations. Acute oral toxicity study of combinatorial gel confirmed the biocompatible and nontoxic characteristics of developed formulation. CONCLUSION: Conclusively, it can be found that nCDDS showed excellent properties regarding drug targeting in a controllable manner as compared to naive PEGylated nanogels.
Authors: Aousaf Ahmad; Mahmood Ahmad; Muhammad Usman Minhas; Muhammad Sarfraz; Muhammad Sohail; Kifayat Ullah Khan; Sana Tanveer; Shakeel Ijaz Journal: Biomed Res Int Date: 2022-07-19 Impact factor: 3.246
Authors: Giuseppina Ioele; Martina Chieffallo; Maria Antonietta Occhiuzzi; Michele De Luca; Antonio Garofalo; Gaetano Ragno; Fedora Grande Journal: Molecules Date: 2022-08-25 Impact factor: 4.927