Case studies of enhanced pharmacodynamic activity of poorly oral bioavailable drugs via solid lipid nanoparticles
Solid lipid nanoparticles (SLNs) considered as an alternative vehicle for the enhanced oral absorption of drugs, and also to enhance therapeutic effectiveness after oral administration. Pharmacodynamic activity of drug is mainly describes the pharmacological and therapeutic activity of drug to the biological system. Lipid nanoparticles especially SLNs made of physiological inert lipid molecules and helps the lymphatic transport. Numerous literatures is available on the effect of SLNs and other colloidal carrier systems on the pharmacokinetic activity of poorly bioavailable drugs, to improve their oral absorption and also respective mechanisms for the improved oral bioavailability. However, very few literatures is reported on the pharmacodynamic activity and the effect of dose on the pharmacodynamic activity. Therefore, the current review is mainly dealing with the effect of SLNs on the pharmacodynamic activity discussed.
Keywords: Oral absorption, solid lipid nanoparticles, lymphatic transport, pharmacokinetics, pharmacodynamics.
2. Andrew JH, William NC, Lipid-based vehicles for the oral delivery of poorly water-soluble drugs, Advanced Drug Delivery Reviews, 1997; 25:103- 128.
3. Alekya T, Narendar D, Mahipal D, Arjun N, Nagaraj B, Design and evaluation of chronomodulated drug delivery of tramadol hydrochloride, Drug research, 2018; 68(03):174-80.
4. Müller RH. Colloidal carriers for controlled drug delivery and targeting: Modification, characterization and in vivo distribution, Taylor & Francis; 1991.
5. Narendar D, Palem CR, Reddy S, Rao YM, Pharmaceutical development and clinical pharmacokinetic evaluation of gastro retentive floating matrix tablets of levofloxacin, International Journal Pharmaceutical Sciences and Nanotechnology, 2011; 4(3):1461-1467.
6. Donthi MR, Dudipala N, Komalla DR, Suram D, Banala N, Design and evaluation of floating multi-unit mini tablets (mumts) muco adhesive drug delivery system of famotidine to treat upper gastro intestinal ulcers. Journal of Pharmacovigilance, 2015; Oct 12.
7. Narendar D, Chinna Reddy P, Sunil R, Madhusudan Rao Y,. Development of floating matrix tablets of Ofloxacin and Ornidazole in combined dosage form: in vitro and in vivo evaluation in healthy human volunteers, International Journal of Drug Delivery, 2012; 4:462-469.
8. Donthi MR, Dudhipala NR, Komalla DR, Suram D, Banala N. Preparation and Evaluation of Fixed Combination of Ketoprofen Enteric Coated and Famotidine Floating Mini Tablets by Single Unit Encapsulation System. Journal of Bioequivalence & Bioavailability. 2015; 7(6):279.
9. Narendar D, Arjun N, Karthik Yadav J, Ramesh B, Amoxycillin trihydrate floating-bioadhesive drug delivery system for eradication of helicobacter pylori: preparation, in vitro and ex vivo evaluation, Journal of bioequvilance bioavailability, 2016; 8(3):118-124.
10. Narendar D, Someshwar K, Arjun N, Madhusudan Rao Y,. Quality by design approach for development and optimization of Quetiapine Fumarate effervescent floating matrix tablets for improved oral delivery, Journal of Pharmaceutical investigation, 2016; 46(3):253-263.
11. Chinna Reddy Palem, Narendar D, Sunil Kumar Battu, Michael A. Repka, Madhusudan Rao Y, Development, optimization and in vivo characterization of domperidone controlled release hot melt extruded films for buccal delivery. Drug Development and Industrail Pharmacy, 2016, 42(3):473-484.
12. Chinna Reddy P Narendar D, Sunil Kumar B, Satyanarayana G, Madhusudan Rao Y, Combined dosage form of pioglitazone and felodipine as mucoadhesive pellets via hot melt extrusion for improved buccal delivery with application of quality by design approach, Journal of drug delivery science and technology, 2015; 30:209-219.
13. Banala N, Peddapalli H, Dudhipala N, Chinnala KM, Transmucosal delivery of duloxetine hydrochloride for prolonged release: preparation, in vitro, ex vivo characterization and in vitro-ex vivo correlation. International Journal of Pharmaceutical Sciences and Nanotechnology. 2018; 11(5):4249-58.
14. Palem CR, Ramesh G, Narender D, Vamshi Vishnu Y, Madhusudan Rao Y, Transmucosal delivery of domperidone from bilayered buccal patches: in vitro, ex vivo and in vivo characterization, Arch pharmacal research, 2011; 34(10):1701-1710.
15. Swetha E, Narendar D, Influence of β-Cyclodextrin and hydroxypropyl-β-cyclodextrin on enhancement of solubility and dissolution of isradipine, International Journal Pharmaceutical Sciences and Nanotechnology, 2017; 10(3):3752-3757.
16. Palem CR, Reddy ND, Satyanarayana G, Varsha BP, Development and optimization of Atorvastatin calcium-cyclodextrin inclusion complexed oral disintegrating tablets for enhancement of solubility, dissolution, pharmacokinetic and pharmacodynamic activity by central composite design, International Journal Pharmaceutical Sciences and Nanotechnology, 2016; 9(2):1-11.
17. Butreddy A, Narendar D, Enhancement of solubility and dissolution rate of trandolapril sustained release matrix tablets by liquisolid compact approach, Asian Journal of Pharmaceutics, 2015; 9(4):290-297.
18. Narendar D, Arjun N, Sunitha K, Harika K, Nagaraj B, Development of osmotically controlled oral drug delivery systems of tramadol hydrochloride: effect of formulation variables on in-vitro release kinetics, Asian Journal of Pharmaceutics, 2016; 10(3):1-10.
19. Arjun N, Narendar D, Sunitha K, Harika K, Madhusudan Rao Y, Nagaraj B, Development, evaluation and influence of formulation and process variables on in vitro performance of oral elementary osmotic device of atenolol, International Journal of Pharmaceutical Investigation, 2016; 6(4):1-9.
20. Pitta SK, Dudhipala N, Narala A, Veerabrahma K, Development and evaluation of zolmitriptan transfersomes by Box-Behnken design for improved bioavailability by nasal delivery, Drug Development and Industrial Pharmacy, 2018; 44(3):484-492.
21. Narendar D, Riyaz PMD, Ahmed AY, Nagaraj B, Effect of lipid and edge activator concentration on development of Aceclofenac loaded transfersomes gel for transdermal application: in vitro and ex vivo skin permeation, Drug Development and Industrial Pharmacy, 2020; 46(8):1334-1344.
22. Rajitha R, Narendar D, Arjun N, Mahipal D, Nagaraj B. Colon delivery of naproxen: preparation, characterization and in vivo evaluation, International Journal Pharmaceutical Sciences and Nanotechnology, 2016; 9(3): 1-10.
23. Nagaraj B, Anusha K, Narendar D, Sushma P, Formulation and evaluation of microemulsion-based transdermal delivery of duloxetine hydrochloride, International Journal of Pharmaceutical Sciences and Nanotechnology, 2020; 13(1):4773-82.
24. Shruthi K, Narendar D, Arjun N, Kishan V, Development and Antimicrobial Evaluation of Binary Ethosomal Topical Gel of Terbinafine Hydrochloride for the Treatment of Onychomycosis, International Journal Pharmaceutical Sciences and Nanotechnology, 2018; 11:3998-4005.
25. Narendar D, Arjun N, Ramesh B, Recent Updates in the formulation strategies to enhance the bioavailability of drugs administered via intranasal route, Journal of bioequivalence and bioavailability, 2016; 8(5):204-207.
26. Bruce JA, Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism, Journal of Pharmaceutical scienecs, 1993; 82(10):979-987.
27. Doodipala R, A review of novel formulation strategies to enhance oral delivery of zaleplon, Journal of bioequivalence and bioavailability, 2016; 8(5):211-213.
28. Mehnert W, Mäder K, Solid lipid nanoparticles production, characterization and applications, Advanced Drug Delivery Reviews, 2012; 64:83-101.
29. Dudhipala N, Influence of solid lipid nanoparticles on pharmacodynamic activity of poorly oral bioavailable drugs, International Journal of Pharmaceutical Sciences and Nanotechnology, 2020; 13(4):4979-83.
30. Müller RH, Mäder K, Gohla S, Solid lipid nanoparticles (SLN) for controlled drug delivery a review of the state of the art, European Journal of Pharmaceutics and Biopharmacokinetics, 2000; 50:161-177.
31. Banala N, Tirumalesh C, Suram D, Dudhipala N, Zotepine loaded lipid nanoparticles for oral delivery: preparation, characterization, and in vivo pharmacokinetic studies, Future Journal of Pharmaceutical Sciences, 2020; 6(1):37.
32. Wissing SA, Kayser O, Muller RH, Solid lipid nanoparticles for parenteral drug delivery, Advanced Drug Delivery Reviews, 2004; 56:1257–72.
33. Banala N, Cernam T, Suram D, Dudhipala N, Design, development and in vivo pharmacokinetic evaluation of zotepine loaded solid lipid nanoparticles for enhanced oral bioavailability, ACTA Pharmaceutica Sciencia, 2020.
34. Schwarz C, Solid lipid nanoparticles (SLN) for controlled drug delivery II. Drug incorporation and physicochemical characterization, Journal of Microencapsulation, 1999; 16(2):205-213.
35. Narendar D, Karthik Yadav J, Thirupathi G, Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation, Artificial cells, nanomedicine biotechnology, 2018; 46(S2):616-625.
36. Tirumalesh C, Suram D, Dudhipala N, Banala N, Enhanced pharmacokinetic activity of Zotepine via nanostructured lipid carrier system in Wistar rats for oral application, Pharmaceutical Nanotechnology, 2020; 8(2):158-160.
37. Suvarna G, Narender D, Kishan V, Preparation, characterization and in vivo evaluation of rosuvastatin calcium loaded solid lipid nanoparticles, International Journal Pharmaceutical Sciences and Nanotechnology, 2015; 8(1):2779-2785.
38. Ahmed AAY, Narendar D, Mujumdar S, ciprofloxacin loaded nanostructured lipid carriers incorporated into in-situ gels to improve management of bacterial endophthalmitis, Pharmaceutics, 2020; 12(6):572.
39. Arun B, Narendar D, Kishan V, Development of olmesartan medoxomil lipid based nanoparticles and nanosuspension: Preparation, characterization and comparative pharmacokinetic evaluation, Artificial cells, nanomedicine biotechnology, 2018; 46(1):126-137.
40. Nagaraj K, Narendar D, Kishan V, Development of olmesartan medoxomil optimized nanosuspension using Box-Behnken design to improve oral bioavailability, Drug Development and Industrial Pharmacy, 2017; 43(7):1186-1196.
41. Karri V, Butreddy A, Narender D, Fabrication of efavirenz freeze dried nanocrystals: formulation, physicochemical characterization, in vitro and ex vivo evaluation, Advanced Science, Engineering and Medicine, 2015; 7(5):385-392.
42. Almeida AJ, Eliana S, Solid lipid nanoparticles as a drug delivery system for peptides and proteins, Advanced Drug Delivery Reviews, 2007; 59(6):478-490.
43. Narendar D, A comprehensive review on solid lipid nanoparticles as delivery vehicle for enhanced pharmacokinetic and pharmacodynamic activity of poorly soluble drugs. International Journal Pharmaceutical Sciences and Nanotechnology, 2019; 12(2):4421-4440.
44. Luo Y, Teng Z, Li Y, Wang Q, Solid lipid nanoparticles for oral drug delivery: chitosan coating improves stability, controlled delivery, mucoadhesion and cellular uptake, Carbohydrate polymers, 2015; 122:221-229.
45. Mehnert W, Mäder K, Solid lipid nanoparticles production, characterization and applications, Advanced Drug Delivery Reviews, 2001; 47:165-196.
46. Müller RH, Schwarz C, Zur Muhlen A, et al, Incorporation of lipophilic drugs and drug release profiles of solid lipid nanoparticles (SLN). Proc Int Symp Control Rel Bioact Mate, 1994; 21:146–7.
47. Tatke A, Dudhipala N, Janga KY, et al, In situ gel of triamcinolone acetonide-loaded solid lipid nanoparticles for improved topical ocular delivery: tear kinetics and ocular disposition studies, Nanomaterials (Basel), 2019; 27:9(1).
48. Müller RH, Mehnert W, Lucks JS, Schwarz C, Zur Mühlen A, Weyhers H, Freitas C, Ruhl D, Solid lipid nanoparticles (SLN) - An alternative colloidal carrier system for controlled drug delivery, European Journal of Pharmaceutics and Biopharmacokinetics,1995; 41:62–69.
49. Usha KG, Narendar D, Veerabrahma K, Preparation, characterization and in vivo evaluation of felodipine solid lipid nanoparticles to improve the oral bioavailability, International Journal Pharmaceutical Sciences and Nanotechnology, 2015; 8 (4):1-8.
50. Müller RH, Maaûen, S Weyhers H, et al, Cytotoxicity of magnetite loaded polylactide, polylactide/glycolide particles and solid lipid nanoparticles (SLN), International Journal of Pharmaceutics, 1996;138:85- 94.
51. Sandeep V, Arjun N, Kishan V, Lacidipine loaded solid lipid nanoparticles for oral delivery: Preparation, characterization and in vivo evaluation, International Journal Pharmaceutical Sciences and Nanotechnology, 2016; 9(6):3524-30.
52. Venkateswarlu V, Manjunath K, Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles, Journal of Controlled Release, 2004; 95:627–38.
53. Dudhipala N, Ahmed AAY, Nagaraj B, Colloidal lipid nanodispersion enriched hydrogel of antifungal agent for management of fungal infections: comparative in-vitro, ex-vivo and in-vivo evaluation for oral and topical application, Chemistry and Physics of Lipids, 2020: 104981.
54. Dudhipala N, Ay AA, Amelioration of ketoconazole in lipid nanoparticles for enhanced antifungal activity and bioavailability through oral administration for management of fungal infections, Chemistry and Physics of Lipids, 2020; 232:104953.
55. Göppert TM, Müller RH, Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: Comparison of plasma protein adsorption patterns, Journal of Drug Targeting, 2005; 13(3):179-187.
56. Narendar D, Govardhan K, Capecitabine lipid nanoparticles for anti-colon cancer activity in 1, 2-dimethylhydrazine induced colon cancer: Preparation, cytotoxic, pharmacokinetic and pathological evaluation, Drug Development and Industrial Pharmacy, 2018; 44(10):1572-1582.
57. Uner M, Wissing SA, Yener G, et al, Investigation of skin moisturizing effect and skin penetration of ascorbyl palmitate entrapped in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) incorporated into hydrogel, Pharmazie, 2005b; 60:751–5.
58. Narendar D, Karthik J, Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: Optimization, in vitro and in vivo evaluation, Drug Development and Industrail Pharmacy, 2017; 43(7):1205-1214.
59. Zariwala MG, Elsaid N, Jackson TL, et al,). A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles, International Journal of Pharmaceutics, 2013; 456(2):400-407.
60. Pandita D, Kumar S, Poonia N, Lather V, Solid lipid nanoparticles enhance oral bioavailability of resveratrol, a natural polyphenol, Food Research International, 2014; 62:1165-1174.
61. Dudhipala N, Gorre T, Neuroprotective effect of ropinirole lipid nanoparticles enriched hydrogel for parkinson’s disease: In vitro, ex vivo, pharmacokinetic and pharmacodynamic evaluation, Pharmaceutics, 2020; 12(5):448.
62. Ji H, Tang J, Li M, Ren J, Zheng N, Wu L, Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin, Drug Delivery, 2016; 23:459-470.
63. Padhye SG, Mangal SN, Simvastatin Solid lipid nanoparticles for oral delivery: formulation development and in vivo evaluation, Indian Journal of Pharmaceutical Sciences, 2013; 75(5):591-598.
64. Narendar D, Kishan V, Pharmacokinetic and pharmacodynamic studies of nisoldipine loaded solid lipid nanoparticles by central composite design. Drug Development and Industrial Pharmacy, 2015; 41(12):1968-1977.
65. Narendar D, Kishan V, Candesartan cilexetil nanoparticles for improved oral bioavailability, Therapeutic delivery, 2017; 8(2):79-88.
66. Medhi B, Misra S, Sinha VR, Modi M, Galantamine-loaded solid lipid nanoparticles: Preparation, characterization, and pharmacodynamics evaluations, Alzheimer's and Demen, 2015; 11(7):840-890.
67. Narendar D, Kishan V, Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation, Drug Delivery, 2016; 23(2):395-404.
68. Chiara D, Federica F, Benedetta F, Arianna CR, et al, Solid lipid nanoparticles delivering anti-inflammatory drugs to treat inflammatory bowel disease: TEMP effects in an in vivo model, World Journal of gastroenterology, 2017; 23(23):4200-4210.
69. Narendar D, Kishan V, Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: pharmacokinetic and pharmacodynamic evaluation. European Journal of Pharmaceutics and Biopharmacokinetics, 2017; 110(1):47-57.
70. Thirupathi G, Swetha E, Narendar D, (2017). Role of isradipine loaded solid lipid nanoparticles in the pharmacodynamic effect of isradipine in rats, Drug research, 2017; 67(03):163-169
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).