International Journal of Nanoscience and Nanotechnology

International Journal of Nanoscience and Nanotechnology

Purified Compound of the Seeds of Carica Papaya Loaded mPEG-PLA Polymeric Nanomicelle (MCPI-PNs) for Reproductive Studies in Albino Male Rats

Document Type : Research Paper

Authors
Abdul S. Ansari
Rajeev Kumar Dhaked
Barkha Khilwani
Nirmal K. Lohiya
Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur, Rajasthan 302004, India
10.22034/ijnn.2024.2007929.2418
Abstract
   This study compares the characterized MCP I-loaded methoxy poly (ethylene glycol)-poly (lactic acid) polymeric nanomicelles (MCPI-PNs) of different sizes and doses to find out the maximum antireproductive effects with purified compound of seeds of Carica papaya. The prepared MCPI-PNs consisting of six groups (n=36), viz., vehicle treated control (group 1), alone MCP I @ 10 mg/animal/day (group 2), 46.03 nm sized blank mPEG-PLA nanomicelles @ 0.3 mL/animal/day (group 3), 100 nm sized MCPI-PNs (1.5, 3.0 and 4.5 µg/animal/day) (group 4), 129 nm sized MCPI-PNs (4.5, 9.0 and 13.5 µg/animal/day) (group 5) and 166 nm sized MCPI-PNs (13.5, 27.0 and 45.0 µg/animal/day) (group 6) were orally treated for a period of 30 days in albino male rats. Animals of groups 2, 4, 5 and 6 showed significantly altered sperm parameters. However, the sperm concentration maximally dropped in group 2 and 4 (low dose and mid dose), respectively, indicating the range of oligozoospermia to severe oligozoospermia in these groups. The fertility declined to zero percent in groups 2 and 4 (low dose), whereas all animals were 100% fertile in rest of groups. Histopathological studies of testes exhibited sloughing and eruption of germ cells with inhibition of spermatogenesis in groups 2 and 4, whilst some conspicuous alterations in spermatogenesis was observed in groups 5 and 6 when compared to groups 1 and 3. Based on the above observations, the group 4 (100 nm sized MCPI-PNs) at low dose regimen (1.5 µg/animal/day) exhibited maximum antifertility effects in male albino rats.
Keywords
Drug delivery systems
mPEG-PLA polymeric nanomicelles
MCPI-PNs
Reproductive effects
Male albino rats
Subjects
  1. Lohiya NK, Goyal RB “Antifertility investigations on the crude chloroform extract of Carica papaya seeds in male albino rats”, Indian J Exp Biol, 30 (1992) 1051–1055.
  2. Lohiya NK, Pathak N, Mishra PK, Manivannan B, “Reversible contraception with chloroform extract of Carica papaya seeds in male rabbits”, Reprod Toxicol 13 (1999) 59–66.
  3. Lohiya NK, Mishra PK, Pathak N, Manivannan B, Jain SC “ Reversible azoospermia by oral administration of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rabbits”, Adv Contracept 15 (1999) 141–61.
  4. Pathak N, Mishra PK, Manivannan B and Lohiya NK., “Sterility due to inhibition of sperm motility by oral administration of benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats”, Phytomedicine 7 (2000) 325-333.
  5. Ansari AS, Shrivastava S, Goyal S and Lohiya NK., “Observations on chromosomal aberrations following treatment with methanol sub-fraction (MSF) of Carica papaya seeds for contraception in albino rats and rabbits”, Int J Pharmacol 7(6) (2011) 721-725.
  6. Lohiya NK, Manivannan B, Mishra PK and Pathak N., “Prospects of developing a plant based male contraceptive pill”, In: Chaudhury SR, Gupta CM, Kamboj VP, editors. Current Status in Fertility Regulation: Indigenous and Modern Approaches. Lucknow: Central Drug Research Institute; (2001) 99-119.
  7. Lohiya NK, Mishra PK, Pathak N, Manivannan B and Bhande SS., “Efficacy trial on the purified compounds of the seeds of Carica papaya for male contraception in albino rat”, Reprod Toxicol 20 (2005) 135-148.
  8. Lohiya, NK, Pathak N, Mishra PK and Manivannan B., “Contraceptive evaluation and toxicological study of aqueous extract of the seeds of Carica papaya in male rabbits”, J Ethnopharmacol 70 (2000) 17-27.
  9. Haensler J and Szoka FC Jr., “Polyamidoamine cascade polymers mediate efficient transfection of cells in culture”, Bioconjug Chem 4 (1993) 372-379.
  10. Kukowska-Latallo JF, Bielinska AU, Johnson J, Spindler R, Tomalia DA and Baker JR., “Efficient transfer of genetic material into mammalian cells using starburst polyamidoamine dendrimers”, Proc Natl Acad Sci USA 93 (1996) 4897-4902.
  11. Yu T, Liu X, Bolcato-Bellemin AL, Wang Y, Liu C, Erbacher P, Qu F, Rocchi P, Behr JP, Peng L., “An amphiphilic dendrimer for effective delivery of small interfering RNA and gene silencing in vitro and in vivo. Angew”, Chem Int Ed Engl 51 (2012) 8478-8484.
  12. Liu X, Zhou J, Yu T, Chen C, Cheng Q, Sengupta K, Huang Y, Li H, Liu C, Wang Y, Posocco P, Wang M, Cui Q, Giorgio S, Fermeglia M, Qu F, Pricl S, Shi Y, Liang Z, Rocchi P, Rossi JJ, Peng L., “Adaptive amphiphilic dendrimer-based nanoassemblies as robust and versatile siRNA delivery systems”, Chem Int Ed Engl 53 (2014) 11822-11827.
  13. Choi JS, Nam K, Park JY, Kim JB, Lee JK, Park JS., “Enhanced transfection efficiency of PAMAM dendrimer by surface modification with L-arginine”, J Controlled Release 99 (2004) 445-456.
  14. Yang HJ, Cho WG and Park SN., “Stability of oil-in-water nano-emulsions prepared using the phase inversion composition method”, J Ind Eng Chem 15 (2009) 331-335.
  15. Kang EB, Sharker SM, In I and Park SY., “Pluronic mimicking fluorescent carbon nanoparticles conjugated with doxorubicin via acid-cleavable linkage for tumor-targeted drug delivery and bioimaging”, J Ind Eng Chem 43 (2016) 150-157.
  16. Pourjavadi A, Tehrani ZM, Shirvani T, Doulabi M and Bumajdad A., “Dendritic multi-walled carbon nanotube with thermoresponsive shells: A good carrier for anticancer drugs”, J Ind Eng Chem 35 (2016) 332-340.
  17. Kukreja A, Kang B, Kim H-O, Jang E, Son HY, Huh Y-M and Haam, “Preparation of gold core-mesoporous iron-oxide shell nanoparticles and their application as dual MR/CT contrast agent in human gastric cancer cells”, J Ind Eng Chem 48 (2017) 56-65.
  18. Lim GH and Choi HJ., “Synthesis of self-assembled rectangular-shaped polyaniline nanotubes and their physical characteristics”, J Ind Eng Chem 47 (2017) 51-55.
  19. Zhao X, Zou X and Ye L., “Controlled pH-and glucose-responsive drug release behavior of cationic chitosan-based nano-composite hydrogels by using graphene oxide as drug nanocarrier”, J Ind Eng Chem 49 (2017) 36-45.
  20. Gong J, Chen M, Zheng Y, Wang S and Wang Y., “Polymeric micelles drug delivery system in oncology”, Control. Release 159 (2012) 312-323.
  21. Zhang Y, Huang Y and Li S., “Polymeric Micelles: Nanocarriers for Cancer-Targeted Drug Delivery”, AAPS Pharm Sci Tech 15 (2014) 862-871.
  22. Yokoyama M., “Polymeric micelles as a new drug carrier system and their required considerations for clinical trials”, Expert Opin Drug Deliv 7 (2010) 145-158.
  23. Amirmahani N, Mahmoodi NO, Galangash MM, and Ghavidast A., “Advances in nanomicelles for sustained drug delivery”, J Ind Eng Chem 55 (2017) 21–34.
  24. Li Z, Guo Z, Chu D, Feng H, Zhang J, Zhu L and Li J., “Effectively suppressed angiogenesis-mediated retinoblastoma growth using celastrol nanomicelles”, Drug Deliv 27 (2020) 358-366.
  25. Márquez-Miranda V, Camarada MB, Araya-Durán I, Varas-Concha I, Almonacid DE, González-Nilo FD., “Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers”, PLoS ONE 10(9) (2015) e0138392. https://doi.org/10.1371/journal.pone.0138392
  26. Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). Guidelines on the Regulation of Scientific Experiments on Animals, Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). New Delhi, India: Standard Operating Procedures (SOP) for Institutional Animals Ethics Committee (IAEC), Animal Welfare Division, Ministry of Environment, Forests and Climate Change, Government of India; (2010).
  27. Hsiue GH, Lo CL, Lin SJ and Tsai HC., “Stable micelles formed with diblock copolymers of critical micelle concentration copolymer and temperature-sensitive copolymer”, US patent US8299178 B2.
  28. Yasugia K, Nagasakia Y, Katoa M and Kataokab K., “Preparation and characterization of polymer micelles from poly (ethylene glycol)-poly (D, L lactide) block copolymers as potential drug carrier”, J Control Release 62 (1999) 89-100.
  29. Zhao H, Liu Z, Park S, Kim SH, Kim JH and Piao L., “Preparation and Characterization of PEG/PLA Multiblock and Triblock Copolymer”, Bull Korean Chem Soc 33 (2012) 1-5.
  30. Giita Silverajah VS, Ibrahim NA, Yunus WMZW, Hassan HA and Woei CB., “A Comparative Study on the Mechanical, Thermal and Morphological Characterization of Poly (lactic acid)/Epoxidized Palm Oil Blend”, Int J Mol Sci 13 (2012) 5878-5898.
  31. Zhao M, Li M, Zhang Z, Gong T and Sun X., “Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA”, Drug Deliv 23 (2015) 2596-2607.
  32. Xiaozhou S, Lei L and Weihan H., “Characterization of the spindle morphology nanomicelles assembled from sericin and gelatin”, J Nanomater 2017 (2017) 1-10.
  33. Xue Y, Qian X, Keyu S, Zhijie L, Dong D and Baojian, “Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles”, Int J Nanomedicine 12 (2017) 4981-4989.
  34. “WHO Laboratory Manual for Examination and Processing of the Human Semen”, Ed. 5. WHO Press, Geneva, (2017).
  35. Wei T, Chen C, Liu J, Liu C, Posocco P, Liu X, Cheng Q, Huo S, Liang Z, Fermeglia M, Pricl S, Liang XJ, Rocchi P and Peng L., “Anticancer drug nanomicelles formed by self assembling amphiphilic dendrimer to combat cancer drug resistance”, Proc Natl Acad Sci 112 (2015) 2978-2983.
  36. Mourya VK, Inamdar N, Nawale RB and Kulthe SS., “Polymeric micelles: General considerations and their applications”, Ind J Pharm Edu Res 45(2) (2011) 128-138.
  37. Webber SE., “Polymer micelles: An example of self assembling polymers”, J Phys Chem B 102 (1998) 2618-2626.
  38. Kabanov AV, Batrakova EV and Alakhov VY., “Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery”, J Control Release 82 (2002) 189-212.
  39. Ordanini S. and Cellesi F., “Complex polymeric architectures self-assembling in unimolecular micelles: Preparation, characterization and drug nanoencapsulation”, Pharmaceutics 10(209) (2018) 1-19.
  40. Jette KK, Law D, Schmitt EA and Kwon GS., “Preparation and drug loading of poly (ethylene glycol)-block-poly(å-caprolactone) micelles through the evaporation of a cosolvent azeotrope”, Pharm Res 21 (2004) 1184-91.
  41. Gohy JF., “Block copolymer micelles”, Adv Polym Sci 190 (2005) 65-36.
  42. Prabaharan M, Grailer JJ, Pilla S, Steeber DA and Gong SQ., “Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn (R.) H40, poly(L-lactide) and poly (ethylene glycol) for tumor-targeted drug delivery”, Biomaterials 30 (2009) 3009–3019.
  43. Yang XQ, Grailer JJ, Pilla S, Steeber DA and Gong SQ., “Tumor-Targeting, pH-Responsive, and Stable Unimolecular Micelles as Drug Nanocarriers for Targeted Cancer Therapy”, Bioconjug Chem 21 (2010) 496–504.
  44. Yang H, Zhao X, Zhang X, Ma L, Wang B, Wei H., “Optimization of bioreducible micelles self-assembled from amphiphilic hyperbranched block copolymers for drug delivery”, J Polym Sci A Polym Chem 56 (2018) 1383–1394.
  45. Zhang X, Zhu T, Miao Y, Zhou L and Zhang W., “Dual responsive doxorubicin loaded nanomicelles for enhanced cancer therapy”. J Nanobiotech 18(1) (2020) 1-17.
  46. Cheng CY and Mruk DD., “The blood-testis barrier and its implications for Male contraception”, Pharmacol Rev 64 (2012) 16–64.
  47. Yuan X, Xie Q, Su K, Li Z, Dong D and Wu, “Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles”, Int. J. Nanomedicine, 12 (2017) 4981–4989.
  48. Lohiya NK, Goyal RB, Jayaprakash D, Sharma S and Kumar M., “Induction of reversible antifertility with a crude ethanol extract of Carica papaya seeds in albino male rats”, Int J Pharmacog 30 (1992) 308-20.
  49. Lohiya NK, Goyal RB, Jayaprakash D, Ansari AS and Sharma S., “Antifertility effects of aqueous extract of Carica papaya seeds in male rats”, Planta Med 60 (1994) 400–404.
  50. Lohiya NK, Goyal RB, Jayaprakash D, Ansari AS and Srivastava S., “Antifertility effects of Carica papaya seeds in male rats”, In: Puri CP, Van Look PFA, editors. Current Concepts in Fertility Regulation and Reproduction. New Delhi: Wiley Eastern Ltd. (1994) 177–192.
  51. Manivannan B, Mittal R, Goyal S, Ansari AS and Lohiya NK., “Sperm characteristics and testis ultrastructure”, Asian J Androl 11 (2009) 583–599
  52. Lohiya NK, Manivannan B and Garg S., “Toxicological investigations on the methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats”, Reprod Toxicol 22 (2006) 461-468.
  53. Lohiya NK, Manivannan B, Goyal S and Ansari AS., “Sperm motility inhibitory effect of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in langur monkey, Presbytis entellus entellus”, Asian J Androl 10 (2008) 298-306.
International Journal of Nanoscience and Nanotechnology
Volume 20, Issue 2
2024
Pages 77-90