Sustained-release ketamine-loaded nanoparticles fabricated by sequential nanoprecipitation

Nanoprecipitation: Applications for Entrapping Active Molecules of Interest in Pharmaceutics

“…Figure 2 shows in a comparative way the reported starting materials used to prepare the different types of particles via nanoprecipitation. As can be seen, PLGA, PCL, and PLA are the most used polymers to prepare polymeric nanoparticles and when these polymers are chemically modified with, for example, PEG, stealth polymeric nanoparticles can be obtained [16,17,27]. Surfactants of low HLB value, e.g., soy phospholipids, could be added to the organic phase for facilitating the particle formation [19,31] and, if nanocapsules are intended, castor oil, sesame oil, caprylic capric triglycerides, and caprylic capric triglyceride PEG-4 esters are part of the organic phase.…”

“…Thus, the aqueous phases are solutions of stabilizing agents as poloxamer, polyvinyl alcohol, and polysorbate 80, which prevent the particle aggregation phenomena. Likewise, aqueous phases can only be water [16] or phosphate buffer [27,59].…”

“…Stability of the particle dispersions has been investigated by using refrigerated storage [6,8,13,15,21], room temperature at 25°C [8,13,14,21,57], and accelerated conditions varying between 35 and 40°C [8,9,11,20,27]. Particle size, PDI, and zeta potential are usually followed during the storage time, and the physical integrity of the dispersions is observed for up to 6 months.…”

“…Regarding the carriers prepared by nanoprecipitation, among the reported developments of particles that could theoretically allow them a better in vivo performance are: (i) particle sizes lesser than 100 nm for polymeric nanospheres [25,26,34], solid lipid nanoparticles [71], and hybrid nanoparticles [7,34,56], (ii) positively charged polymeric nanospheres by using chitosan [72] and Eudragit ® RL 100 [18] as polymers or positively charged hybrid nanoparticles prepared from lipids as the stearylamine [5], (iii) stealth polymeric nanospheres [17,27] and stealth hybrid particles [4][5][6][7][8], and (iv) targeted cancer hybrid particles [7,59].…”

“…Some of the research works undertaken during the last years have proposed the vectorization in nanoparticles, via nanoprecipitation, of hydrophobic active molecules, mainly exhibiting logP values higher than 3. They include antineoplastics (e.g., doxorubicin [4], paclitaxel [5,6], docetaxel [7,8], methotrexate [9], triptolide [6], cucurbitacin [10], and sorafenib [11]), antiretrovirals (e.g., efavirenz [12] and nevirapine [13]), immune suppressants (mycophenolate [14]), anti-inflammatories (clobetasol [15], fluticasone propionate [16], dexamethasone [17,18], and diclofenac [19]), antimicrobial and antifungal agents (polymyxin B [20], amphotericin B [21], itraconazole [22], and linezolid [23]), antihyperlipidemics (fenofibrate [24,25]), anesthetics (tetracaine [26] and ketamine [27]), antihypertensives (nimodipine [28] and atenolol [29]), vitamins or their precursors (β-carotene [30] and vitamin E [31]), and antioxidants (quercetin [14,32]). Likewise, although in a much smaller number, hydrophilic active molecules such alendronate [33], N-acetylcysteine [34], and calcein [35], have been investigated.…”