Modern Technologies of Controlled Release of Biologically Active Substances in Pharmaceutical Research and Development (Review)
https://doi.org/10.33380/2305-2066-2020-9-2-56-66
Abstract
Introduction. The review describes various systems used as inclusion matrices or modifiers of biologically active substances to enhance their absorption or deposition and subsequent release, both continuous or «on demand», i.e. in response to a stimulus.
Text. Technologies for the incorporation of active substances into cyclodextrin nanoaggregates are developed to the greatest extent. Such technologies were used to obtain modified forms of hydrocortisone, glibenclamide, and a number of peptide drugs. Acetylcysteine immobilized on ethyl cellulose or other polymer particles significantly increases the bioavailability of peptide drugs on their intranasal administration. The deposition of active substances in the body takes place by way of their delayed controlled dissolution, adsorption, encapsulation, or esterification. The release of deposited substances upon exposure to an endogenous (change in pH, temperature) or external (exposure to ultrasound, electric or magnetic field, chemical activators) stimulus can be single or multiple, depending on the ability of the accommodating matrix for self-aggregation.
Conclusion. Self-aggregated peptides are most promising for stimulus-induced release/delivery of biologically active substances. Modern technologies for the modification of active substances increase the efficiency of their administration and favor targeted location and implementation time of biological effects.
About the Author
E. I. Savelieva
Research Institute of Hygiene, Occupational Pathology and Human Ecology Federal State Unitary Enterprise, Federal Medical Biological Agency
Russian Federation
Russian Federation
Elena I. Savelieva
build. 93, Kapitolovo station, g/p Kuz’molovsky, Vsevolzskiy district, Leningrad Region, 188663
References
1. Demina N. B. Current Trends in the Development of Technologies for Matrix Formulations with Modified Release. Pharmaceutical Chemistry Journal. 2016; 50(7): 475–480. DOI: 10.1007/s11094-016-1472-4.
2. Krasnuk (Junior) I. I., Ovsyannikova L. V., Stepanova O. I., Belyatskaya A. V., Krasnuk I. I., Kharitonov Y. Y., Grikh V. V., Kosheleva T. M., Korol L. A. Application of solid dispersions with non steroidal anti inflammatory drugs in pharmacy. Drug development & registration. 2016; 2(15): 40–44. DOI: 10.1007/s11094-018-1799-0 (in Russ.).
3. Kuznetsova I. G., Dubovik E. G., Dubovik N. S., Komarov T. N., Medvedev Yu. V., Men’shikova L. A., Severin S. E., Shohin I. E., Yarushok T. A. Biodistribution of the polymer transport form of rifabutin. Bulletin of RAMS. 2015; 70 (3): 366–371. DOI: 10.15690/vramn.v70i3.1335 (in Russ).
4. Loftsson T., Brewster M. E. Pharmaceutical applications of cyclodextrins: basic science and product development. J PharmPharmacol. 2010; 62(11): 1607–1621. DOI: 10.1111/j.2042-7158.2010.01030.x.
5. Gracheva I. M. Biotechnology of biologically active substances. Textbook for students of higher educational institutions. – M.: Publishing house of NPO «Elevar». 2006: 453 (in Russ).
6. Kedik S. A., Panov A. V., Tyukova V. S., Zolotareva M. S. Cyclodextrins and their application in pharmaceutical industry. Drug development & registration. 2016; 3(16): 68–75 (in Russ).
7. Morrison P. W. J., Connon Ch. J., Khutoryanskiy V. V. CyclodextrinMediated Enhancement of Riboflavin Solubility and Corneal Permeability. Molecular Pharmaceutics. 2013; 10(2): 756–762. DOI: 10.1021/mp3005963.
8. Scantlebery A. M., Ochodnicky P., Kors L. et al. β-cyclodextrin counteracts obesity in western diet-fed mice but elicits a nephrotoxic effect. Scientific Reports. 2019; 9: 17633. DOI: 10.1038/s41598-019-53890-z.
9. Messner M., Kurkov S. V., Brewster M. E., Jansook P., Loftsson T. Selfassembly of cyclodextrin complexes: Aggregation of hydrocortisone/ cyclodextrin complexes. International Journal of Pharmaceutics. 2011; 407: 174–183. DOI: 10.1016/j.ijpharm.2011.01.011.
10. Wu Ch., Xie O., Xu W., Tu M., Jiang L. Lattice self-assembly of cyclodextrin complexes and beyond Current. Opinion in Colloid & Interface Science. 2019; 39: 76–85. DOI: 10.1016/j.cocis.2019.01.002
11. Lucio D., Martinez-Oharriz M. C., Gonzalez-Navarro C. J., NavarroHerrera D., Gonzalez-Gaitano G., Radulescu A., Irache J. M. Coencapsulation of cyclodextrins into poly (anhydride) nanoparticles to improve the oral administration of glibenclamide. A screening on C. elegans. Colloids and surfaces Biointerfaces. 2017. (163): 64–72. DOI: 10.1016/j.colsurfb.2017.12.038.
12. Lucio D., Martinez-Oharriz M. C., Gu Z., He Y., Aranaz P., Vizmanos J. L., Irac he J. M. Cyclodextrin-grafted poly (anhydride) nanoparticles for oral glibenclamide administration. In vivo evaluation using C. elegans. Int J Pharm. 2018; 547(1-2): 97–105. DOI: 10.1016/j.ijpharm.2018.05.064.
13. Srinivasan M., Rajabi M., Mousa S. A. Multifunctional Nanomaterials and Their Applications in Drug Delivery and Cancer Therapy. Nanomaterials. 2015; 5(4): 1690–1703. DOI: 10.3390/nano5041690.
14. Chaves P. D., Ourique A. F., Frank L. A., Pohlmann A. R., Guterres S. S., Beck R. C. Carvedilol-loaded nanocapsules: Mucoadhesive properties and permeability across the sublingual mucosa. European journal of pharmaceutics and biopharmaceutics. 2017; 114: 88–95. DOI: 10.1016/j.ejpb.2017.01.007.
15. Vega E., Egea M. A., Garduno-Ramirez M. L., Garcia M. L., Sanchez E., Espina M., Calpena A. C. Flurbiprofen PLGA-PEG nanospheres: role of hydroxy-beta-cyclodextrin on ex vivo human skin permeation and in vivo topical anti-inflammatory efficacy. Colloids and surfaces. B, Biointerfaces. 2013; 110: 339–346. DOI: 10.1016/j.colsurfb.2013.04.045.
16. Li I., Zhang J., Wang Z., Yao Y., Han X., Zhao Y., Liu J., Zhang S. Identification of a cyclodextrin inclusion complex of antimicrobial peptide CM4 and its antimicrobial activity. Food Chemistry. 2017; 221: 296–301. DOI: 10.1016/j.foodchem.2016.10.040.
17. Demina N. B. Biopharmaceutical classificatiom system as a tool for the development of drug formulations and their designs. Drug development & registration. 2017; 2(19): 56–60 (in Russ.).
18. Shingaki T., Hidalgo I. J., Furubayashi T., Sakane T., Katsumi H., Yamamoto A., Yamashita S. Nasal Delivery of P-gp Substrates to the Brain through the Nose–Brain Pathway. Drug Metabolism and Pharmacokinetics. 2011; 26(3): 248–255. DOI: 10.2133/dmpk.dmpk-10-rg-108.
19. Bitter C., Suter-Zimmermann K., Surbera C. Nasal Drug Delivery in Humans. Current Problems in Dermatology. 2011; 40: 20–35. DOI: 10.1159/000321044.
20. Privalova A. M., Bukreeva T. V., Gulyaeva N. V. Intranasal administration: A prospective drug delivery route to the brain. Neurochemical Journal. 2012; 6(2): 77–88. DOI: 10.1134/s1819712412020080 (in Russ.).
21. Horváth T., Ambrus R., Völgyi G., Budai-Szűcs M., Márki Á., Sipos P., Szabó-Révész P. Effect of solubility enhancement on nasal absorption of meloxicam. European Journal of Pharmaceutical Sciences. 2016; 95: 96–102. DOI: 10.1016/j.ejps.2016.05.031.
22. Bartos C., Ambrus R., Sipos P., Budai-Szűcs M., Csányi E., Gáspár R., Márki Á., Seres A. B., Sztojkov-Ivanov A., Horváth T., Szabó-Révész P. Study of sodiumhyaluronate-based intranasal formulations containing micro- or nanosized meloxicamparticles. Int. J. Pharm. 2015; 491(1-2): 198–207. DOI: 10.1016/j.ijpharm.2015.06.046.
23. Deutel B., Laffleur F., Palmberger T., Saxer A., Thaler M., BernkopSchnürch A. In vitro characterization of insulin containing thiomericmicroparticles as nasal drug delivery system. European Journal of Pharmaceutical Sciences. 2016; 81: 157–161. DOI: 10.1016/j.ejps.2015.10.022.
24. Matsuyama T., Takahiro M., Horikiri Y. Influence of fillers in powder formulations containing N-acetyl-L-cysteine on nasal peptide absorption. Journal of Controlled Release. 2007; 120(1-2): 88–94. DOI: 10.1016/j.jconrel.2007.04.006.
25. Bodor N. The soft drug approach. Chemtech. 1984; 14(1): 28–38.
26. Matsuyama T., Morita T., Horikiri Y., Yamahara H., Yoshino H. Improved nasal absorption of salmon calcitonin by powdery formulation with N-acetyl-l-cysteine as a mucolytic agent. Journal of Controlled Release. 2006; 115(2); 183–188. DOI: 10.1016/j.jconrel.2006.08.004.
27. Al-hazmi A. N-acetylcysteine as a therapeutic extract for cardiac, lung, intestine and spleen injuries induced by microcystin-LR in mice. Journal of King Saud University – Science. 2020; 32: 934–938. DOI. 10.1016/j.jksus.2019.06.001.
28. Lee Y., Perry B. A., Labruno S., Lee H. S., Stern W., Falzone L. M., Sinko P. J. Impact of regional intestinal pH modulation on absorption of peptide drugs: oral absorption studies of salmon calcitonin in beagle dogs. Pharmaceutical Research. 1999; 16(8): 1233–1239. DOI: 10.1023/a:1014849630520.
29. Ali A., Wahlgren M., Rembratt-Svensson B., Daftani A., Falkman P., Wollmer P., Engblom J. Dehydration affects drug transport over nasal mucosa. Drug Delivery. 2019; 26(1): 831–840. DOI: 10.1080/10717544.2019.1650848.
30. He C., Zhuang X., Tang Z., Tian H., Chen X. Stimuli-Sensitive Synthetic Polypeptide-Based Materials for Drug and Gene Delivery. Advanced Healthcare Materials. 2011; 1(1): 48–78. DOI: 10.1002/adhm.201100008.
31. Kricheldorf H. R. Polypeptides and 100 Years of Chemistry of α-Amino AcidN-Carboxyanhydrides. Angewandte Chemie International Edition. 2006; 45(35): 5752–5784. DOI: 10.1002/anie.200600693.
32. Shah A., Malik M. S., Khan G. S., Nosheen E., Iftikhar F. J., Khan F. A., Aminabhavi T. M. Stimuli-responsive peptide-based biomaterials as drug delivery systems. Chemical Engineering Journal. 2018; 353: 559–583. DOI: 10.1016/j.cej.2018.07.126.
33. Matson J. B., Zha R. H., Stupp S. I. Peptide self-assembly for crafting functional biological materials. Current Opinion in Solid State and Materials Science. 2011; 15(6): 225–235. DOI: 10.1016/j.cossms.2011.08.001.
34. Wong S., Shim M. S., Kwon Y. J. Synthetically designed peptide-based biomaterials with stimuli-responsive and membrane-active properties for biomedical applications. J. Mater. Chem. B. 2014; 2(6): 595–615. DOI: 10.1039/c3tb21344g.
35. Sankaranarayanan K., Meenakshisundaram N. Micro-viscosity induced conformational transitions in poly-l-lysine. RSC Adv. 2016; 6(78): 74009–74017. DOI: 10.1039/c6ra11626d.
36. Ito Y., Park Y. S., Imanishi Y. Nanometer-sized channel gating by a selfassembled polypeptide brush. Langmuir. 2000; 16(12): 5376–5381. DOI: 10.1021/la991102+.
37. Lee E. S., Shin H. J., Na K., Bae Y. H. Poly(l-histidine) – PEG block copolymer micelles and pH-induced destabilization. Journal of Controlled Release. 2003; 90(3): 363–374. DOI: 10.1016/s0168-3659(03)00205-0.
38. Chang G., Li C., Lu W., Ding J. N-Boc-Histidine-Capped PLGA-PEG-PLGA as a Smart Polymer for Drug Delivery Sensitive to Tumor Extracellular pH. Macromolecular Bioscience. 2010; 10(10): 1248–1256. DOI: 10.1002/mabi.201000117.
39. Chen P., Qiu M., Deng C., Meng F., Zhang J., Cheng R., Zhong Z. pHResponsive Chimaeric Pepsomes Based on Asymmetric Poly(ethylene glycol)-b-Poly(l-leucine)-b-Poly(l-glutamic acid) Triblock Copolymer for Efficient Loading and Active Intracellular Delivery of Doxorubicin Hydrochloride. Biomacromolecules. 2015; 16(4): 1322–1330. DOI: 10.1021/acs.biomac.5b00113.
40. Yan J., Liu K., Zhang X., Li W., Zhang A. Dynamic covalent polypeptides showing tunable secondary structures and thermoresponsiveness. Journal of Polymer Science Part A: Polymer Chemistry. 2014; 53(1): 33–41. DOI: 10.1002/pola.27433.
41. Hassouneh W., Zhulina E. B., Chilkoti A., Rubinstein M. Elastinlike Polypeptide Diblock Copolymers Self-Assemble into Weak Micelles. Macromolecules. 2015; 48(12): 4183–4195. DOI: 10.1021/acs.macromol.5b00431.
42. Ward M. A., Georgiou T. K. Thermoresponsive Polymers for Biomedical Applications. Polymers. 2011; 3(3): 1215–1242. DOI: 10.3390/polym3031215.
43. Schwendeman S. P., Shah R. B., Bailey B. A., Schwendeman A. S. Injectable controlled release depots for large molecules. Journal of Controlled Release. 2014; 190: 240–253. DOI: 10.1016/j.jconrel.2014.05.057.
44. Rosenthal R. N., Ling W., Casadonte P., Vocci F., Bailey G. L., Kampman K., Beebe K. L. Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction. 2013; 108(12): 2141– 2149. DOI: 10.1111/add.12315.
45. Narukawa T., Soh J., Kanemitsu N., Harikai S., Ukimura O. Efficacy of combined treatment of intramuscular testosterone injection and testosterone ointment application for late-onset hypogonadism: an open-labeled, randomized, crossover study. The Aging Male. 2019: 1–7. DOI: 10.1080/13685538.2019.1666814.
46. Bowersock T. L., Martin S. Vaccine delivery to animals. Advanced Drug Delivery Reviews. 1999; 38(2): 167–194. DOI: 10.1016/s0169-409x(99)00015-0.
47. Dubey A., Shami T. Metamaterials in Electromagnetic Wave Absorbers.Defence Science Journal. 2012; 62(4): 261–268. DOI: 10.14429/dsj.62.1514.
48. Dunn R. L., English J. P., Cowsar D. R., Vanderbelt D. D. Biodegradable in-situ forming implants and methodfor producing the same. US Patent 23 Aug. 1994; 5: 340849.
49. Saleem M. A., Ahmed S. I. Tephrosiapurpureaameliorates benzoyl peroxides-induced cutaneoustoxicity in mice: diminution of oxidative stress. Pharm Pharmacol Commun. 1999; 5(7): 455–461. DOI: 10.1211/146080899128735162.
50. Wang L., Venkatraman S., Kleiner L. Drug release from injectable depots: two different in vitro mechanisms. J Control Release. 2004; 99(2): 207–216. DOI: 10.1016/j.jconrel.2004.06.021.
51. Paik D. H., Choi S. W. Entrapment of Protein Using Electrosprayed Poly(d,l-lactide-co-glycolide) Microspheres with a Porous Structure for Sustained Release. Macromolecular Rapid Communications. 2014; 35(11): 1033–1038. DOI: 10.1002/marc.201400042.
52. Brudno Y., Mooney D. J. On-demand drug delivery from local depots. Journal of Controlled Release. 2015; 219: 8–17. DOI: 10.1016/j.jconrel.2015.09.011.
53. Kwok C. S., Mourad P. D., Crum L. A., Self-assembled molecular structures as ultrasonically-responsivebarriermembranes for pulsatile drug delivery. J. Biomed. Mater. Res. 2001; 57(2): 151–164. DOI: 10.1002/1097-4636(200111)57:23.0.co;2-5.
54. Laurent S., Forge D., Port M., Roch A., Robic C., Vander E. L., Muller R. N. ChemInform Abstract: Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications. ChemInform. 2008; 39(35). DOI: 10.1002/chin.200835229.
55. Preiss M. R., Bothun G. D. Stimuli-responsive liposome-nanoparticle assemblies. Expert Opinion on Drug Delivery. 2011; 8(8): 1025–1040. DOI: 10.1517/17425247.2011.584868.
56. Kharitonov Y. Y., Cherkasova O. G., Zavadskiy S. P., Tsybusov S. N., Krasnyuk (Jr) I. I., Grigorjeva V. Y. Quality control of magnetic fillers for magnetic formulations. Drug development & registration. 2016; 3(16): 100–106 (in Russ.).
57. Kharitonov Y. Y., Cherkasova O. G., Zavadskiy S. P., Shabalkina E. Y., Krasnyuk (Jr.) I. I., Grigorjeva V. Y., Tsybusov S. N., Abizov E. A. Development of the procedures of quality control of magnetic medications (magnetic medical ointments, magnetic suppositories, iron-carbon composite for the cryosurgery). Drug development & registration. 2016; (4): 112–117 (in Russ.).
58. Murdan, S. Electro-responsive drug delivery from hydrogels. Journal of Controlled Release. 2003; 92(1-2): 1–17. DOI: 10.1016/s0168-3659(03)00303-1.
59. Murakami Y., Maeda M. DNA-Responsive Hydrogels That Can Shrink or Swell. Biomacromolecules. 2005; 6(6): 2927–2929. DOI: 10.1021/bm0504330.
60. Murakami Y., Maeda M. Hybrid Hydrogels to Which Single-Stranded (ss) DNA Probe Is Incorporated Can Recognize Specific ssDNA. Macromolecules. 2005; 38(5): 1535–1537. DOI: 10.1021/ma047803h.
61. Wang Z. H., Wang Z. Y., Sun C. S., Wang C. Y., Jiang T. Y., Wang S. L. Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain. Biomaterials. 2010; 31(5): 908–915. DOI: 10.1016/j.biomaterials.2009.09.104.
62. Sultana Y., Maurya D. P., Iqbal Z., Aqil M. Nanotechnology in ocular delivery: current and future directions. Drugs Today. 2011; 47(6): 441– 455. DOI: 10.1358/dot.2011.47.6.1549023.
63. Patlolla R. R., Chougule M., Patel A. R., Jackson T., Tata P. N., Singh M. Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers. J Control Release. 2010; 144(2): 233–241. DOI: 10.1016/j.jconrel.2010.02.006.
64. Slutter B., Bal S., Keijzer C., Mallants R., Hagenaars N., Que I. et al. Nasal vaccinationwith N-trimethyl chitosan and PLGA based nanoparticles: nanoparticle characteristics determine quality and strength of the antibody response in mice against the encapsulated antigen. Vaccine. 2010; 28 (38): 6282–6291. DOI: 10.1016/j.vaccine.2010.06.121.
65. Lee P. W., Hsu S. H., Tsai J. S., Chen F. R., Huang P. J., Ke C. J. et al. Multifunctional coreshellpolymeric nanoparticles for transdermal DNA delivery and epidermal langerhans cells tracking. Biomaterials. 2010; 31(8): 2425–2434. Doi: 10.1016/j.biomaterials.2009.11.100.
66. Barry B. W. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001; 14(2): 101–114. DOI: 10.1016/s0928-0987(01)00167-1.
67. Clark S. L., Crowley A. J., Schmidt P. G., Donoghue A. R., Piche C. A. Long-termdelivery of ivermectin by use of poly(D, L-lactic-co-glycolic) acid microparticlesindogs. Am. J. Vet. Res. 2004; 65(6): 752–757. DOI: 10.2460/ajvr.2004.65.752.
68. Camargo J. A., Sapin A., Nouvel C., Daloz D., Leonard M., Bonneaux F., Six J. L., Maincent P. Injectable PLA-based in situ forming implants for controlled releaseof Ivermectin a BCS Class II drug: solvent selection based on physico-chemicalcharacterization. Drug Dev. Ind. Pharm. 2012; 39(1): 146–155. DOI: 10.3109/03639045.2012.660952.
69. Iezzi S., Purslow P., Sara C., Lanusse C., Lifschitz A. Relationship betweenivermectin concentrations at the injection site, muscle and fat of steers treated withtraditional and long-acting preparations. Food and Chemical Toxicology. 2017; 105: 319–321. DOI: 10.1016/j.fct.2017.05.005.
70. Pollock J., Bedenice D., Jennings S. H., Papich M. G. Pharmacokinetics of anextended-release formulation of eprinomectin in healthy adult alpacas and its use inalpacas confirmed with mange. J. Vet. Pharmacol. Ther. 2016; 40(2): 192–199. DOI: 10.1111/jvp.12341.
71. Chen B. Z., Yang Y., Wang B. B., Ashfaq M., Guo, X. D. Self-implanted tiny needles as alternative to traditional parenteral administrations for controlled transdermal drug delivery. International Journal of Pharmaceutics. 2019; 556: 338–348. DOI: 10.1016/j.ijpharm.2018.12.019.
72. Peng H., Qian X., Mao L., Jiang L., Sun Y., Zhou Q. Ultrafast ultrasound imaging in acoustic microbubble trapping. Applied Physics Letters. 2019; 115(20): 203701. DOI: 10.1063/1.5124437.
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Savelieva E.I. Modern Technologies of Controlled Release of Biologically Active Substances in Pharmaceutical Research and Development (Review). Drug development & registration. 2020;9(2):56-66. (In Russ.) https://doi.org/10.33380/2305-2066-2020-9-2-56-66
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