PMID- 28986195 OWN - NLM STAT- MEDLINE DCOM- 20180710 LR - 20180710 IS - 1879-0720 (Electronic) IS - 0928-0987 (Linking) VI - 111 DP - 2018 Jan 1 TI - Surface-modified mucoadhesive microgels as a controlled release system for miconazole nitrate to improve localized treatment of vulvovaginal candidiasis. PG - 358-375 LID - S0928-0987(17)30546-8 [pii] LID - 10.1016/j.ejps.2017.10.002 [doi] AB - The use of conventional vaginal formulations of miconazole nitrate (MN) in the treatment of deep-seated VVC (vulvovaginal candidiasis) is limited by poor penetration capacity and low solubility of MN, short residence time and irritation at the application site. Surface-modified mucoadhesive microgels were developed to minimize local irritation, enhance penetration capacity and solubility and prolong localized vaginal delivery of MN for effective treatment of deep-seated VVC. Solid lipid microparticles (SLMs) were prepared from matrices consisting of hydrogenated palm oil (Softisan(R) 154, SF) and super-refined sunseed oil (SO) with or without polyethylene glycol (PEG)-4000, characterized for physicochemical performance and used to prepare mucoadhesive microgels (MMs) encapsulating MN, employing Polycarbophil as bioadhesive polymer. The MMs were evaluated for physicochemical performance and in vitro drug release in simulated vaginal fluid (pH=4.2), whereas mucoadhesive, rheological and stability tests, anticandidal efficacy in immunosuppressed estrogen-dependent female rats and vaginal tolerance test in rabbits were performed with optimized formulation. The amorphicity of 1:9 phytolipid blend (SO:SF) was increased in the presence of PEG-4000. The physicochemical properties of the SLMs and MMs indicated their suitability for vaginal drug delivery. Overall, MN-loaded PEGylated MMs exhibited significantly (p<0.05) more prolonged drug release than non-PEGylated MMs. Additionally, optimized PEGylated MMs was stable at 40+/-2 degrees C over a period of 6months, viscoelastic, mucoadhesive, non-sensitizing, histopathologically safe and gave remarkably (p<0.05) higher reduction in Candida albicans load (86.06%) than Daktarin(R) (75.0%) and MN-loaded polymeric-hydrogel (47.74%) in treated rats in 12days. Thus, PEGylated MMs is promising for effective and convenient treatment of VVC. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Kenechukwu, Franklin C AU - Kenechukwu FC AD - Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria. Electronic address: frankline.kenechukwu@unn.edu.ng. FAU - Attama, Anthony A AU - Attama AA AD - Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria. FAU - Ibezim, Emmanuel C AU - Ibezim EC AD - Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria. FAU - Nnamani, Petra O AU - Nnamani PO AD - Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria. FAU - Umeyor, Chukwuebuka E AU - Umeyor CE AD - Nanomedicines and Drug Delivery Unit, Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria. FAU - Uronnachi, Emmanuel M AU - Uronnachi EM AD - Nanomedicines and Drug Delivery Unit, Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria. FAU - Gugu, Thaddeus H AU - Gugu TH AD - Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria. FAU - Momoh, Mumuni A AU - Momoh MA AD - Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria. FAU - Ofokansi, Kenneth C AU - Ofokansi KC AD - Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria. FAU - Akpa, Paul A AU - Akpa PA AD - Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria. LA - eng PT - Journal Article DEP - 20171004 PL - Netherlands TA - Eur J Pharm Sci JT - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JID - 9317982 RN - 0 (Antifungal Agents) RN - 0 (Delayed-Action Preparations) RN - 0 (Lipids) RN - 7NNO0D7S5M (Miconazole) SB - IM MH - Adhesiveness MH - Administration, Intravaginal MH - Animals MH - Antifungal Agents/administration & dosage/therapeutic use MH - Candida albicans/drug effects MH - Candidiasis, Vulvovaginal/*drug therapy MH - Delayed-Action Preparations/therapeutic use MH - *Drug Delivery Systems MH - Drug-Related Side Effects and Adverse Reactions MH - Female MH - Hydrogen-Ion Concentration MH - Lipids MH - Miconazole/administration & dosage/*therapeutic use MH - Random Allocation MH - Rats OTO - NOTNLM OT - Cyclophosphamide (PubChem CID: 2907) OT - Estradiol valerate (PubChem CID: 13791) OT - Glycerol (PubChem CID: 753) OT - Methanol (PubChem CID: 887) OT - Miconazole nitrate (MN) OT - Miconazole nitrate (PubChem CID: 68553) OT - Mucoadhesive microgels (MMs) OT - PEG 4000 (PubChem CID: 174) OT - PEGylation OT - Pentylene glycol (PubChem CID: 8105) OT - Polycarbophil (PCP) OT - Solid lipid microparticles (SLMs) OT - Sorbic acid (PubChem CID: 643460) OT - Triethanolamine (PubChem CID: 7618) OT - Tween 80 (PubChem CID: 5284448) OT - Vulvovaginal candidiasis (VVC) EDAT- 2017/10/08 06:00 MHDA- 2018/07/11 06:00 CRDT- 2017/10/08 06:00 PHST- 2017/07/16 00:00 [received] PHST- 2017/09/23 00:00 [revised] PHST- 2017/10/02 00:00 [accepted] PHST- 2017/10/08 06:00 [pubmed] PHST- 2018/07/11 06:00 [medline] PHST- 2017/10/08 06:00 [entrez] AID - S0928-0987(17)30546-8 [pii] AID - 10.1016/j.ejps.2017.10.002 [doi] PST - ppublish SO - Eur J Pharm Sci. 2018 Jan 1;111:358-375. doi: 10.1016/j.ejps.2017.10.002. Epub 2017 Oct 4.