Abstract
Nanoparticles are possible carriers for drug delivery. Copolymer nanoparticles of acrylic acid, acrylic amide, acrylic butylester, and methacrylic methylester (CAA) dispersed in water and in 0.15 M NaCl-solution were investigated by small-angle x-ray scattering (SAXS) experiments. The particles were characterized in terms of parameters relevant for the in vivo distribution: particle shape and diameter, size distribution, surface structure, and their organization within tight systems.
The CAA-nanoparticles exist in at least three populations of spheres with two minor subpopulations having radii of about 32 and 66 nm and the main moiety around 45 nm. The degree of polydispersity isR w/R N=1.05. The subpopulations possess different hydrophobic areas on their surfaces, leading to different recognition by opsonins in vivo and different organ distribution and clearance velocity. The particles are compact without channels and holes, which is proved by low internal hydrationw=0.22 g H2O/g polymer. Drugs and coating surfactants will interact mainly with the outer surface and not tunnel into the carriers. The surface of the nanoparticles is fractal with a dimensionD=2.3. Probe-molecules with dimensions less than 11.4 nm in diameter will find a larger contact area than expected from the sphere radius. Adsorption rate and position of the arrival of surfactants, and possibly opsonins, may be affected thereby. The negative charges on the CAA-nanoparticle surface are nearly completely screened in physiological NaCl-solutions by counter-ions. Therefore, surface charges hamper carrier-cell interaction at short distances only and do not prevent specific recognition and clearance by the reticuloendothelial system (RES).
Similar content being viewed by others
References
Verdun C, Couvreur P, Vranckx H, Lenaerts V, Roland M (1986) J Controlled Release 3:205
Tarcha P (1991) Polymers for Controlled Drug Delivery, CRC Press, Boca Raton Ann Arbor, Boston
Müller RH, Davis SS, Illum L, Mak E (1986) Particle charge and surface hydrophobicity of colloidal drug carriers. In: Gregoriadis S, Senior J, Poste G (eds) Targeting of Drugs with Synthetic Systems) Plenum Press, New York, p 239
Van Oss CJ, Gillman CF, Neumann HW (1975) Phagocytic engulfment and cell adhesiveness as cellular surface phenomena, Marcel Dekker, New York
Van Oss CJ, Gillman CF, Neumann HW (1984) Ann NY Acad Sci 416:332
Müller RH (1991) Colloidal Carriers for Controlled Drug Delivery and Targeting-Modification, Characterization and in Vivo Distribution. Wissenschaftliche Verlagsgesellschaft. CRC Press, Stuttgart/Boca Raton
Kreuter J (1983) Int J Pharm 14:43
Pfeifer P (1987) In: Laszko P (ed) Preperative Chemistry, Academic Press, New York, p 13
Lukowski G, Müller RH, Müller BW, Dittgen M (1992) Int J Pharm 84(1):23
Ametani K, Fujita H (1978) Japanese Journal Appl Physics 17:17
Damaschun G, Pürschel HV (1969b) Monatshefte Chemie 100:274
Müller JJ (1992) In: Programmpaket APX 63, Small-Angle X-Ray Scattering, Freiberger Präzisionsmechanik GmbH, Freiberg, p 1
Marquardt DW (1963) J Soc appl Math 11:431
Glatter O, Kratky O (1982) In: Small-Angle X-ray Seattering. Academic Press, London
Feigin LA, Svergun DI (1987) In: Taylor GW (ed) Structure Analysis by Small-Angle X-Ray and Neutron Scattering, Plenum Press, New York
Walter G, Gerber T, Kranold R (1983) Studia biophysica 97:129
Kratky O, Pilz I, Schmitz PJ (1966) J Colloid and Interface Sci 21:24
Stabinger H, Kratky O (1978) Makrom Chem 179:1655
Plestil J, Pospisil H, Ostanevich Yu M, Degovics G (1991) J Appl Cryst 24:659
Guinier A, Fournet G, Walker CB, Yudowitch KL (1955) In: Small-Angle Scattering of X-Rays. John Wiley & Sons, New York
Enderby JE, March NH (1965) Adv in Physics 14:453
Palmer RG, Weeks JD (1973) J Chem Phys 10:4171
Hayter JB, Penfold J (1981) Molec Physics 42:109
Hansen JP, Hayter JB (1982) Molec Phys 46:651
Fournet G (1951) Acta Cryst 4:293
Zernicke F, Prins JA (1927) Z Physik 41:184
Paalman HH, Pings CJ (1962) J Appl Phys 33:2635
Müller JJ, Zalkova TN, Damaschun G, Misselwitz R, Serdyuk IN, Welfle H (1986) Studia biophysica 112:151
Lukowski G, Müller RH, Müller BW, Dittgen M (1992) Europ J Pharm and Biopharm 38(1):41
Stokes AR (1948) Proc Phys Soc London 61:38
Damaschun G, Pürschel HV (1969) Monatshefte Chemie 100:510
Damaschun G, Müller JJ, Pürschel HV, Sommer G (1969) Monatshefte Chemie 100:1701
Schmidt PW (1991) J Appl Cryst 24:414
Pfeifer P (1984) Appl Surf Sci 18:146
Müller JJ, Damaschun G, Schmidt PW (1985) J Appl Cryst 18:241
Damaschun G, Damaschun H, Dembo AT, Kayushina RL, Kröber R, Moshkov KA, Müller JJ, Neifakh SA, Rolbin JA, Shavlovsky MM, Zirwer D (1978) Studia biophysica 71:53
Cheng CM, Micale FJ, Vanderhoff JW, El-Asser MS (1992) J Colloid Interface Sci 150:549
Verwey EJW, Overbeek JTG (1948) Theory of the stability of lyophobic colloids. Elsevier, Amsterdam
Ise N (1986) Angew. Chemie 98: 323
Dittgen M, Zosel B, Kunze H (1988) Pharmazie 43:872
Lukowski G, Müller RH, Müller BW, Dittgen M (1993) Colloid Polym Sci 271:100
Pfeifer P (1987) In: Laszko P (ed) Preparative Chemistry Academic Press, New York, p 13
Tamai H, Murakami T, Suzawa T (1985) J Appl Polym Sci 30:3857
Shirahama H, Suzawa T (1985) Colloid Polym Sci 263:141
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Müller, J.J., Lukowski, G., Kröber, R. et al. Acrylic acid copolymer nanoparticles for drug delivery: structural characterization of nanoparticles by small-angle x-ray scattering. Colloid Polym Sci 272, 755–769 (1994). https://doi.org/10.1007/BF00652416
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00652416