1111111111111111 IIIIII IIIII 1111111111 11111 lllll 111111111111111 lllll 111111111111111 11111111  US 20200268679Al  c19)  United States  c12)  Patent Application Publication  PRUD’HOMME et al.  c10) Pub. No.: US 2020/0268679 Al  (43) Pub. Date:  Aug. 27, 2020  (54)  HYDROPHOBIC ION PAIRING AND FLASH  NANOPRECIPITATION FOR FORMATION  OF CONTROLLED-RELEASE  NANOCARRIER FORMULATIONS  (71)  Applicant:  The Trustees of Princeton University,  Princeton, NJ (US)  (72)  Inventors:  Robert K. PRUD’HOMME,  Princeton,  NJ (US);  Kurt D. RISTROPH,  Princeton, NJ (US);  Nathalie M.  PINKERTON,  Princeton, NJ (US);  Hoang D. LU,  Princeton, NJ (US);  Paradorn RUMMANEETHORN,  Princeton, NJ (US)  (73)  Assignee:  The Trustees of Princeton University,  Princeton, NJ (US)  (21)  Appl. No.:  16/761,140  (22)  PCT Filed:  Nov. 2, 2018  (86)  PCT No.:  PCT /US2018/058869  § 371 (c)(l),  (2) Date:  May 1, 2020  (60)  Provisional application No. 62/581,394, filed on Nov.  3, 2017.  (51)  Int. Cl.  (52)  U.S. Cl.  CPC ........  A61K 915153  (2013.01);  A61K 3117036  (2013.01);  A61K 38112  (2013.01);  A61K 38/10  (2013.01);  A61K 915192  (2013.01);  A61K  38/38  (2013.01);  A61K 38147  (2013.01);  A61K  915161  (2013.01);  A61K 3115377  (2013.01)  Related U.S. Application Data  Publication Classification  (57)  ABSTRACT  A61K 9151  A61K 3117036  A61K  38112  A61K 38/10  A61K  3115377  A61K 38/38  A61K  38147  (2006.01)  (2006.01)  (2006.01)  (2006.01)  (2006.01)  (2006.01)  (2006.01)  Methods for encapsulating water-soluble biologic and small  molecule active pharmaceutical ingredients (APis) into  nanoparticles by applying nanoprecipitation techniques and  ion-pairing the nanoparticles with hydrophobic counterions  to produce new API salts that exhibit altered solubilities are  presented.  Pre»fnrrried ion paired .AP!  Organic stream  Water stream  iorHpairoo  APi complex  amph!ph!Hc  PCL"’b,,.PEG  staomzer  Organic stream .. Water stream  @jfi  ton-,pak!ng  @  6  reagent  o  0  @ ••  .,  ~::1~1 $^{fifi }$