PMID- 34808068 OWN - NLM STAT- MEDLINE DCOM- 20220216 LR - 20221116 IS - 1744-5116 (Electronic) IS - 1388-0209 (Print) IS - 1388-0209 (Linking) VI - 59 IP - 1 DP - 2021 Dec TI - In vitro-in vivo availability of metformin hydrochloride-PLGA nanoparticles in diabetic rats in a periodontal disease experimental model. PG - 1576-1584 LID - 10.1080/13880209.2021.2002369 [doi] AB - CONTEXT: Metformin is an important oral anti-hyperglycemic used in diabetes. Polylactic-co-glycolic acid (PLGA) has been widely used due to its reliability in controlling the release of drugs. OBJECTIVE: This study evaluates the in vitro-in vivo availability of metformin hydrochloride-loaded polylactic-co-glycolic acid. MATERIAL AND METHODS: In vitro metformin release (Met-free or PLGA + Met-12.5 mg/mL per 360 min) was evaluated using static Franz vertical diffusion cells. The in vivo study was performed with two control groups (validation bioanalytical method) and two experimental groups of diabetic male Wistar rats treated with PLGA + Met 10 mg/kg or Met 100 mg/kg by oral gavage. Diabetes was induced by streptozotocin (40 mg/kg) through the penile vein. Blood samples were collected 0.5, 1, 4, 7, 10, 12, 18, 24, 36, 48 and 72 h and analysed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: PLGA + Met 10 mg/kg was released in the in vitro assay suggesting a parabolic diffusion kinetic model (K -0.0619(-0.5h)) with a 100% release profile in 10 h by controlled diffusion. The in vivo assay showed the apparent volume of distribution Vz/F (PLGA + Met 10 mg/kg, 40971.8 mL/kg vs. Met 100 mg/kg, 2174.58 mL/kg) and mean residence time MRTinf (PLGA + Met 10 mg/kg, 37.66 h vs. Met 100 mg/kg, 3.34 h). DISCUSSION AND CONCLUSIONS: The formulation modifies pharmacokinetics parameters such as apparent distribution volume and mean residence time. The PLGA + Met 10 mg/kg had a slower elimination rate compared to Met 100 mg/kg in diabetic rats in a periodontal disease experimental model. FAU - Pereira, Aline de Sousa Barbosa Freitas AU - Pereira ASBF AD - Post-Graduation Program in Oral Science, Department of Dentistry, UFRN, Natal, Brazil. FAU - de Souza Lima, Maria Laura AU - de Souza Lima ML AD - Post-Graduation Program in Oral Science, Department of Dentistry, UFRN, Natal, Brazil. FAU - da Silva-Junior, Arnobio Antonio AU - da Silva-Junior AA AD - Postgraduate Program in Pharmaceutical Science, Federal University of Rio Grande do Norte, Natal, Brazil. FAU - Dos Santos Silva, Emanuell AU - Dos Santos Silva E AUID- ORCID: 0000-0002-9849-4496 AD - Postgraduate Program in Pharmaceutical Science, Federal University of Rio Grande do Norte, Natal, Brazil. FAU - de Araujo Junior, Raimundo Fernandes AU - de Araujo Junior RF AUID- ORCID: 0000-0003-2349-2354 AD - Post-Graduation program in Functional and Structural Biology/Post-graduation program Health Science/Department of Morphology, UFRN, Natal, Brazil. FAU - Martins, Agnes Andrade AU - Martins AA AD - Department of Dentistry, UFRN, Natal, Brazil. FAU - Alves, Jovelina Samara Ferreira AU - Alves JSF AD - Drug Quality Control Laboratory (LCQMed), Department of Pharmacy, UFRN, Natal, Brazil. FAU - Oliveira, Artur de Santana AU - Oliveira AS AD - Drug Quality Control Laboratory (LCQMed), Department of Pharmacy, UFRN, Natal, Brazil. FAU - De Santis Ferreira, Leandro AU - De Santis Ferreira L AUID- ORCID: 0000-0002-8408-5886 AD - Drug Quality Control Laboratory (LCQMed), Department of Pharmacy, UFRN, Natal, Brazil. FAU - de Araujo Costa, Emily Cintia Tossi AU - de Araujo Costa ECT AD - Institute of Chemistry, UFRN, Natal, Brazil. FAU - Guerra, Gerlane Coelho Bernardo AU - Guerra GCB AD - Post-Graduation Program in Biochemistry and Molecular Biology/Post-Graduation Program in Pharmaceutical Science, Department of Biophysics and Pharmacology, UFRN, Natal, Brazil. FAU - de Medeiros, Caroline Addison Carvalho Xavier AU - de Medeiros CACX AD - Post-Graduation Program in Biochemistry and Molecular Biology/Post-Graduation Program in RENORBIO, Department of Biophysics and Pharmacology, UFRN, Natal, Brazil. FAU - Brito, Gerly A C AU - Brito GAC AD - Postgraduate Program in Pharmacology, Postgraduate Program in Morphology, Department of Morphology, UFC, Fortaleza, Brazil. FAU - de Carvalho Leitao, Renata Ferreira AU - de Carvalho Leitao RF AD - Postgraduate Program in Morphology, Department of Morphology, UFC, Fortaleza, Brazil. FAU - de Araujo, Aurigena Antunes AU - de Araujo AA AUID- ORCID: 0000-0001-9264-4695 AD - Post-Graduation Program Oral Science/Post-Graduation Program in Pharmaceutical Science, Department of Biophysics and Pharmacology, UFRN, Natal, Brazil. LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Pharm Biol JT - Pharmaceutical biology JID - 9812552 RN - 0 (Drug Carriers) RN - 0 (Hypoglycemic Agents) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 5W494URQ81 (Streptozocin) RN - 9100L32L2N (Metformin) SB - IM MH - Animals MH - Biological Availability MH - Chromatography, High Pressure Liquid MH - Diabetes Mellitus, Experimental/*drug therapy MH - Dose-Response Relationship, Drug MH - Drug Carriers/chemistry MH - Drug Liberation MH - Hypoglycemic Agents/*administration & dosage/pharmacokinetics MH - Male MH - Metformin/*administration & dosage/pharmacokinetics MH - Nanoparticles MH - Periodontal Diseases/*drug therapy MH - Polylactic Acid-Polyglycolic Acid Copolymer/chemistry MH - Rats MH - Rats, Wistar MH - Streptozocin MH - Tandem Mass Spectrometry MH - Tissue Distribution PMC - PMC8635670 OTO - NOTNLM OT - Polylactic-co-glycolic acid OT - bioavailability OT - diabetes COIS- No potential conflict of interest was reported by the author(s). EDAT- 2021/11/23 06:00 MHDA- 2022/02/17 06:00 PMCR- 2021/11/22 CRDT- 2021/11/22 20:11 PHST- 2021/11/22 20:11 [entrez] PHST- 2021/11/23 06:00 [pubmed] PHST- 2022/02/17 06:00 [medline] PHST- 2021/11/22 00:00 [pmc-release] AID - 2002369 [pii] AID - 10.1080/13880209.2021.2002369 [doi] PST - ppublish SO - Pharm Biol. 2021 Dec;59(1):1576-1584. doi: 10.1080/13880209.2021.2002369.