Rilpivirine-loaded solid lipid nanoparticles: preparation, characterization, and in vivo evaluation for enhancing oral bioavailability

Articles in Press

Document Type : Research Paper

Authors

Department of Pharmaceutics, AISSMS College of Pharmacy, Pune, India

10.22038/nmj.2026.86737.2190

Abstract

Objective(s): This study aimed to improve the oral bioavailability of Rilpivirine by creating and testing Rilpivirine solid lipid nanoparticles (SLNs) to determine the impact of drug delivery on pharmacokinetics following oral treatment in Wistar rats.
Materials and Methods: Solid lipid nanoparticles (SLNs) were fabricated using a high-pressure homogenization technique, after which they were evaluated for their physicochemical properties including particle size, morphology, zeta potential, encapsulation efficiency as well as their in vitro release behaviour, ex vivo permeability, and in vivo pharmacokinetics in Wistar rats. To further understand how SLNs are taken up through the lymphatic system, an ex vivo study was carried out using an everted rat intestinal sac model.
Results: The resulting SLNs were spherical, showing an average particle size of 74.45 ± 0.84 nm with a PDI of 0.27, zeta potential -17.49 ± 0.82 mV, and an entrapment efficiency of 62.9 ± 1.2%. The SLN formulation demonstrated 84% drug release over a 24-hour period. In an ex vivo study using everted rat intestine, the SLN's apparent permeability was 34.2 × 10-6 at 37 ± 0.5 °C without chlorpromazine. This value decreased to 14.6 × 10-6 when chlorpromazine was present. Pharmacokinetic studies in rats showed the SLN formulation's AUC was 1.04 times higher than that of the pure drug suspension. Conversely, adding the lymphatic uptake inhibitor chlorpromazine reduced the SLN's AUC by 0.52-fold. The in vivo pharmacokinetic data was assessed by Dunnett's test, which indicated a significant difference (p < 0.05) between the RLV SLNs and the plain RLV drug.
Conclusion: Employing SLNs as a delivery vehicle appears to be a viable method for boosting the therapeutic efficacy of rilpivirine. A key reason is that SLN lymphatic uptake is important for avoiding hepatic first-pass metabolism.

Keywords

References

  1. Govender RD, Hashim MJ, Khan MA, Mustafa H, Khan G. Global epidemiology of HIV/AIDS: A resurgence in North America and Europe. J Epidemiol Glob Health. 2021;11(3):296–301.
  2. Hammer SM, Saag MS, Schechter M, Montaner JSG, Schooley RT, Jacobsen DM, et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA. 2006;296 (7):827–843.
  3. James C, Preininger L, Sweet M. Rilpivirine: a second-generation nonnucleoside reverse transcriptase inhibitor. Am J Health-Syst Pharm AJHP Off J Am Soc Health-Syst Pharm. 2012;69 (10):857–861.
  4. Seneviratne HK, Tillotson J, Lade JM, Bekker LG, Li S, Pathak S, et al. Metabolism of long-acting rilpivirine after intramuscular injection: HIV prevention trials network study 076 (HPTN 076). AIDS Res Hum Retroviruses. 2021;37(3):173–183.
  5. Zainuddin R, Zaheer Z, Sangshetti JN, Momin M. Enhancement of oral bioavailability of anti-HIV drug rilpivirine HCl through nanosponge formulation. Drug Dev Ind Pharm. 2017; 43 (12):2076–2084.
  6. kommavarapu P, Maruthapillai A, Palanisamy K, Sunkara M. Preparation and characterization of rilpivirine solid dispersions with the application of enhanced solubility and dissolution rate. Beni-Suef Univ J Basic Appl Sci. 2015;4(1):71–79.
  7. Suresh G, Manjunath K, Venkateswarlu V, Satyanarayana V. Preparation, characterization, and in vitro and in vivo evaluation of lovastatin solid lipid nanoparticles. AAPS PharmSciTech. 2007; 8(1):E162–E170 .
  8. Makwana V, Jain R, Patel K, Nivsarkar M, Joshi A. Solid lipid nanoparticles (SLN) of efavirenz as lymph targeting drug delivery system: elucidation of mechanism of uptake using chylomicron flow blocking approach. Int J Pharm. 2015;495(1):439–446.
  9. Bhalekar MR, Upadhaya PG, Madgulkar AR, Kshirsagar SJ, Dube A, Bartakke US. In-vivo bioavailability and lymphatic uptake evaluation of lipid nanoparticulates of darunavir. Drug Deliv. 2016;23(7):2581–2586.
  10. Trevaskis NL, Charman WN, Porter CJH. Lipid-based delivery systems and intestinal lymphatic drug transport: a mechanistic update. Adv Drug Deliv Rev. 2008;60(6):702–716.
  11. Silva AC, González-Mira E, García ML, Egea MA, Fonseca J, Silva R, et al. Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SLN): high pressure homogenization versus ultrasound. Colloids Surf B Biointerfaces. 2011;86(1):158–165.
  12. Hao J, Fang ,Xinsheng, Zhou ,Yanfang, Wang ,Jianzhu, Guo ,Fengguang, Li ,Fei, et al. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design. Int J Nanomedicine. 2011;6: 683–692.
  13. Varshosaz J, Tabbakhian M, Mohammadi MY. Formulation and optimization of solid lipid nanoparticles of buspirone HCl for enhancement of its oral bioavailability. J Liposome Res. 2010; 20(4):286–296.
  14. Chadha R, Bhandari S. Drug-excipient compatibility screening--role of thermoanalytical and spectroscopic techniques. J Pharm Biomed Anal. 2014;87:82–97.
  15. Ebrahimi HA, Javadzadeh Y, Hamidi M, Jalali MB. Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles. Daru. 2015;23 (1):46-56.
  16. Ravi PR, Vats R, Dalal V, Murthy AN. A hybrid design to optimize preparation of lopinavir loaded solid lipid nanoparticles and comparative pharmacokinetic evaluation with marketed lopinavir/ritonavir coformulation. J Pharm Pharmacol. 2014;66(7):912–926.
  17. Lind ML, Jacobsen J, Holm R, Müllertz A. Intestinal lymphatic transport of halofantrine in rats assessed using a chylomicron flow blocking approach: the influence of polysorbate 60 and 80. Eur J Pharm Sci Off J Eur Fed Pharm Sci. 2008;35(3):211–218.
  18. Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006;29(3–4):278–287.
  19. Bhalekar M, Upadhaya P, Madgulkar A. Formulation and characterization of solid lipid nanoparticles for an anti-retroviral drug darunavir. Appl Nanosci. 2017;7(1):47–57.
  20. Kumar BMS, Rajkamal B, Chandramowli B. Development and validation of rilpivirine in pharmaceutical formulation by RP-HPLC. Am J PharmTech Res. 2019;9(3):344–353.
  21. Ali Khan A, Mudassir J, Mohtar N, Darwis Y. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations. Int J Nanomedicine. 2013;8:2733–2744.
  22. Mahmoudian M, Valizadeh H, Zakeri-Milani P. Bortezomib-loaded solid lipid nanoparticles: preparation, characterization, and intestinal permeability investigation. Drug Dev Ind Pharm. 2018;44(10):1598–1605.
  23. Tadros T. Chapter 2 - Colloid and interface aspects of pharmaceutical science. In Colloid and interface science in pharmaceutical research and development. 2014:29-54
  24. Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm. 2007;66(2):227–243.
  25. Honary S, Zahir F. Effect of zeta Potential on the properties of nano-drug delivery systems - A review (Part 2). Trop J Pharm Res. 2013;12(2):265–273.
  26. Huma R, Saeed A, Asadullah M, Iqra R, Mohammed G, Umme H, et al. Compritol-based alprazolam solid lipid nanoparticles for sustained release of alprazolam: preparation by hot melt encapsulation. Molecules. 2022;27(24):8894.
  27. Karla L, Andrea R, Jose A, Flavia Z. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) prepared by microwave and ultrasound-assisted synthesis: promising green strategies for the nanoworld. Pharmaceutics. 2023;15(5):1333.
  28. Carine P, Fabiola M, Jelver R, Frederico P, Adny S, Paula S, Angela C, Tania P. Influence of surfactant and lipid type on the physicochemical properties and biocompatibility of solid lipid nanoparticles. Int J Environ Res Public Health. 2014; 11(8): 8581-8596.
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Articles in Press, Accepted Manuscript
Available Online from 10 June 2026

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