Development and Evaluation of Ketoconazole Loaded Nano-sponges for Topical Drug Delivery
DOI:
https://doi.org/10.37285/ijpsn.2018.11.4.2Abstract
Beta-cyclodextrin nanosponges (NS) based hydrogel had been studied as a topical delivery of ketoconazole (KTZ) for effective eradication of cutaneous fungal infection. The purpose of the present study was to develop KTZ loaded NS for topical drug delivery with skin targeting to minimizing the adverse side effects and providing a controlled release. The four types of NS were synthesized by varying the molar ratios of β-cyclodextrin (β-CD) to diphenylcarbonate (DPC) as a cross linker viz. 1:2, 1:4, 1:6, and 1:8. The KTZ loaded NS shows particle size 274.6-367 nm and high loading efficacy was obtained, FTIR, DSC, XRD studies confirmed the complexation of KTZ with NS. Hydrogel were evaluated comparatively with commercial product with respect to physicochemical properties, ex-vivo skin permeation and skin retention on human cadaver skin and antifungal activity. Ex-vivo study of KTZ-NS hydrogel exhibited controlled drug release up to 8 hrs whereas skin retention studies show avoidance of the systemic uptake and better accumulative uptake of the drug compared to marketed formulation. The zone of inhibition of KTZ-NS hydrogel was higher in comparison with commercial formulation against Candida albicans. These results indicate that the KTZ-NS is having controlled drug release, potential of skin targeting with enhanced antifungal activity.
Downloads
Download data is not yet available.
Metrics
Metrics Loading ...
Keywords:
β-cyclodextrin nanosponges, ketoconazole, hydrogel, antifungal, ex-vivo permeation
Downloads
Published
2018-07-31
How to Cite
1.
Pardeshi HA, Gambhire MS, Gujar KN, Vaidhya AA. Development and Evaluation of Ketoconazole Loaded Nano-sponges for Topical Drug Delivery. Scopus Indexed [Internet]. 2018 Jul. 31 [cited 2024 May 18];11(4):4154-62. Available from: https://www.ijpsnonline.com/index.php/ijpsn/article/view/377
Issue
Section
Research Articles
References
Alam MA, Ahmad FJ, Khan ZI, Khar RK, and Ali M (2007). Development and evaluation of acid-buffering bio adhesive vaginal tablet for mixed vaginal infections. AAPS Pharm Sci Tech 8(4): 229-36.
Amrutiya N, Bajaj A, and Madan M (2009). Development of micro sponges for topical delivery of mupirocin. AAPS Pharm Sci Tech 10(2): 402-9.
Ansari KA, Vavia PR, Trotta F, and Cavalli R (2011) Cyclodextrin-based nanosponges for delivery of resveratrol: In vitro characterisation, stability, cytotoxicity and permeation study. AAPS Pharm Sci Tech 12(1): 279-86.
Bhalekar MR, Pokharkar V, Madgulkar A, Patil N, and Patil N (2009). Preparation and evaluation of miconazole nitrate loaded solid lipid nanoparticle for topical delivery. AAPS Pharm Sci Tech 10(1): 289-96.
Biked ML, Nathani AH, Mandlik SK, Shrotriya SN, and Ranpise NS (2014). Halobetasol propionate-loaded solid lipid nanoparticle (SLN) for skin targeting by topical delivery. Journal of Liposome Research 24(2): 113-23.
Cavalli R, Trotta F, and Tumiatti W (2006). Cyclodextrin-based nanosponges for drug delivery. Journal of Inclusion Phenomena and Macro Cyclic Chemistry 56(1-2): 209-13.
Dureja H, Tiwary AK, and Gupta S (2001). Simulation of skin permeability in chitosan membranes. International Journal of Pharmaceutics 213(1): 193-8.
Elmoslemany RM, Abdallah OY, El-Khordagui LK and Khalafallah NM (2012). Propylene glycol liposome’s as a topical delivery system for miconazole nitrate: comparison with conventional liposomes. AAPS Pharm Sci Tech 13(2): 723-31.
Ge S, Lin Y, Lu H, Li Q, He J, Chen B, Wu C, and Xu Y (2014). Percutaneous delivery of econazole using micro emulsion as vehicle: formulation, evaluation and vesicle-skin interaction. International Journal of Pharmaceutics 465(1): 120-31.
Higuchi T and Connors KA (1965). Phase solubility techniques. Advances in Analytical Chemistry and Instrumentation
4: 212-217.
Jain S, Jain S, Khare P, Gulbake A, Bansal D, and Jain SK (2010). Design and development of solid lipid nanoparticle for topical delivery of an anti-fungal agent. Drug Delivery 17(6): 443-51.
Lembo D, Swaminathan S, Donalisio M, Civra A, Pastero L, Aquilano D, Vavia P, Trotta F, and Cavalli R (2013). Encapsulation of Acyclovir in new carboxylated cyclodextrin-based nanosponges improves the agent's antiviral efficacy. International Journal of Pharmaceutics 443(1): 262-72.
Patel MR, Patel RB, Parikh JR, Solanki AB, and Patel BG (2011). Investigating effect of micro emulsion components: In vitro permeation of ketoconazole. Pharmaceutical Development and Technology 16(3): 250-8.
Sahoo S, Pani NR, and Sahoo SK (2014). Microemulsion based topical hydrogel of sertaconazole: Formulation, characterization and evaluation. Colloids and Surfaces B: Bio interfaces 120: 193-9.
Sharma R and Pathak K (2011). Polymeric nanosponges as an alternative carrier for improved retention of econazole nitrate onto the skin through topical hydrogel formulation. Pharmaceutical Development and Technology 16(4): 367-76.
Shringirishi M, Prajapati SK, Mahor A, Alok S, Yadav P, and Verma A (2014). Nanosponges: a potential nanocarrier for novel drug delivery-a review. Asian Pacific Journal of Tropical Disease 4(2): 19-26.
Souto EB and Müller R H (2005). SLN and NLC for topical delivery of ketoconazole. Journal of Microencapsulation 22(5): 501-10.
Swaminathan S, Vavia PR, Trotta F, and Torne S (2007). Formulation of betacyclodextrin based nanosponges of itraconazole. Journal of Inclusion Phenomena and Macro cyclic Chemistry 57(1-4): 89-94.
Swaminathan S, Pastero L, Serpe L, Trotta F, Vavia P, Aquilano D, Trotta M, Zara G, and Cavalli R (2010). Cyclodextrin-based nanosponges encapsulating camptothecin: physicochemical characterization, stability and cytotoxicity. European Journal of Pharmaceutics and Bio pharmaceutics 74(2): 193-201.
Torne S, Darandale S, Vavia P, Trotta F, and Cavalli R (2013). Cyclodextrin-based nanosponges: effective nanocarrier for Tamoxifen delivery. Pharmaceutical Development and Technology 18(3): 619-25.
Torne SJ, Ansari KA, Vavia PR, Trotta F, and Cavalli R (2010). Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded nanosponges. Drug Delivery. 17(6): 419-25.
Trotta F, Cavalli R, Tumiatti W, Zerbinati O, Roggero C, Vallero R. Ultrasound-assisted synthesis of cyclodextrin based nanosponges. (US Patent: WO2006/002814)
Trotta F, Zanetti M, and Cavalli R (2012). Cyclodextrin based nanosponges as drug carriers. Beilstein Journal of Organic Chemistry 8(1): 2091-9.
Trotta F and Cavalli R. (2009). Characterization and applications of new hyper-cross linked cyclodextrin. Composite Interfaces 16(1): 39-48.
Rao M, Bajaj A, Khole I, Munjapara G, and Trotta F (2013). In vitro and in vivo evaluation of β-cyclodextrin-based nanosponges of telmisartan. Journal of Inclusion Phenomena and Macro Cyclic Chemistry 77(1-4): 135-45.
Amrutiya N, Bajaj A, and Madan M (2009). Development of micro sponges for topical delivery of mupirocin. AAPS Pharm Sci Tech 10(2): 402-9.
Ansari KA, Vavia PR, Trotta F, and Cavalli R (2011) Cyclodextrin-based nanosponges for delivery of resveratrol: In vitro characterisation, stability, cytotoxicity and permeation study. AAPS Pharm Sci Tech 12(1): 279-86.
Bhalekar MR, Pokharkar V, Madgulkar A, Patil N, and Patil N (2009). Preparation and evaluation of miconazole nitrate loaded solid lipid nanoparticle for topical delivery. AAPS Pharm Sci Tech 10(1): 289-96.
Biked ML, Nathani AH, Mandlik SK, Shrotriya SN, and Ranpise NS (2014). Halobetasol propionate-loaded solid lipid nanoparticle (SLN) for skin targeting by topical delivery. Journal of Liposome Research 24(2): 113-23.
Cavalli R, Trotta F, and Tumiatti W (2006). Cyclodextrin-based nanosponges for drug delivery. Journal of Inclusion Phenomena and Macro Cyclic Chemistry 56(1-2): 209-13.
Dureja H, Tiwary AK, and Gupta S (2001). Simulation of skin permeability in chitosan membranes. International Journal of Pharmaceutics 213(1): 193-8.
Elmoslemany RM, Abdallah OY, El-Khordagui LK and Khalafallah NM (2012). Propylene glycol liposome’s as a topical delivery system for miconazole nitrate: comparison with conventional liposomes. AAPS Pharm Sci Tech 13(2): 723-31.
Ge S, Lin Y, Lu H, Li Q, He J, Chen B, Wu C, and Xu Y (2014). Percutaneous delivery of econazole using micro emulsion as vehicle: formulation, evaluation and vesicle-skin interaction. International Journal of Pharmaceutics 465(1): 120-31.
Higuchi T and Connors KA (1965). Phase solubility techniques. Advances in Analytical Chemistry and Instrumentation
4: 212-217.
Jain S, Jain S, Khare P, Gulbake A, Bansal D, and Jain SK (2010). Design and development of solid lipid nanoparticle for topical delivery of an anti-fungal agent. Drug Delivery 17(6): 443-51.
Lembo D, Swaminathan S, Donalisio M, Civra A, Pastero L, Aquilano D, Vavia P, Trotta F, and Cavalli R (2013). Encapsulation of Acyclovir in new carboxylated cyclodextrin-based nanosponges improves the agent's antiviral efficacy. International Journal of Pharmaceutics 443(1): 262-72.
Patel MR, Patel RB, Parikh JR, Solanki AB, and Patel BG (2011). Investigating effect of micro emulsion components: In vitro permeation of ketoconazole. Pharmaceutical Development and Technology 16(3): 250-8.
Sahoo S, Pani NR, and Sahoo SK (2014). Microemulsion based topical hydrogel of sertaconazole: Formulation, characterization and evaluation. Colloids and Surfaces B: Bio interfaces 120: 193-9.
Sharma R and Pathak K (2011). Polymeric nanosponges as an alternative carrier for improved retention of econazole nitrate onto the skin through topical hydrogel formulation. Pharmaceutical Development and Technology 16(4): 367-76.
Shringirishi M, Prajapati SK, Mahor A, Alok S, Yadav P, and Verma A (2014). Nanosponges: a potential nanocarrier for novel drug delivery-a review. Asian Pacific Journal of Tropical Disease 4(2): 19-26.
Souto EB and Müller R H (2005). SLN and NLC for topical delivery of ketoconazole. Journal of Microencapsulation 22(5): 501-10.
Swaminathan S, Vavia PR, Trotta F, and Torne S (2007). Formulation of betacyclodextrin based nanosponges of itraconazole. Journal of Inclusion Phenomena and Macro cyclic Chemistry 57(1-4): 89-94.
Swaminathan S, Pastero L, Serpe L, Trotta F, Vavia P, Aquilano D, Trotta M, Zara G, and Cavalli R (2010). Cyclodextrin-based nanosponges encapsulating camptothecin: physicochemical characterization, stability and cytotoxicity. European Journal of Pharmaceutics and Bio pharmaceutics 74(2): 193-201.
Torne S, Darandale S, Vavia P, Trotta F, and Cavalli R (2013). Cyclodextrin-based nanosponges: effective nanocarrier for Tamoxifen delivery. Pharmaceutical Development and Technology 18(3): 619-25.
Torne SJ, Ansari KA, Vavia PR, Trotta F, and Cavalli R (2010). Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded nanosponges. Drug Delivery. 17(6): 419-25.
Trotta F, Cavalli R, Tumiatti W, Zerbinati O, Roggero C, Vallero R. Ultrasound-assisted synthesis of cyclodextrin based nanosponges. (US Patent: WO2006/002814)
Trotta F, Zanetti M, and Cavalli R (2012). Cyclodextrin based nanosponges as drug carriers. Beilstein Journal of Organic Chemistry 8(1): 2091-9.
Trotta F and Cavalli R. (2009). Characterization and applications of new hyper-cross linked cyclodextrin. Composite Interfaces 16(1): 39-48.
Rao M, Bajaj A, Khole I, Munjapara G, and Trotta F (2013). In vitro and in vivo evaluation of β-cyclodextrin-based nanosponges of telmisartan. Journal of Inclusion Phenomena and Macro Cyclic Chemistry 77(1-4): 135-45.
