RESUMEN

Surfactants are crucial in formulating poorly soluble drugs but lead to serious side effects due to PEG chains. Novel supra-amphiphiles consisting of fatty acids and choline are developed, which spontaneously form ionic co-aggregates (ICAs) in water and exhibit strong solubilizing capacity. Paclitaxel (PTX) is adopted as a model drug here to evaluate the feasibility of choline oleate-based ICAs in the intravenous delivery of poorly soluble drugs by comparing the kinetics and distribution of payloads and nanocarriers. Choline oleate presents a maximum 10-fold enhancement in solubilizing capacity to PTX than Cremophor EL (CreEL), enabling a one-tenth use level in the formulation. Aggregation-caused quenching probes are utilized to evaluate the kinetics and biodistribution of ICAs or CreEL-based micelles (MCs). A huge gap is found between the pharmacokinetic and particokinetic curves of either nanocarrier, indicating fast leakage. ICAs lead to faster PTX leakage in blood circulation but higher PTX distribution to organs than MCs. MCs present a longer circulation in blood but a slower distribution to organs than ICAs. ICAs do not arise adverse reactions in rats following repeated injections, while MCs cause pathological changes in varying degrees. In conclusion, choline oleate-based ICAs provide an alternative to surfactants in formulating poorly soluble drugs.

RESUMEN

In vitro permeation test (IVPT) is a frequently used method for in vitro assessment of topical preparations and transdermal drug delivery systems. However, the storage of ex vivo skin for IVPT remains a challenge. Here, two cryopreservation media were chosen to preserve rat and pig skin at -20 °C and -80 °C for further IVPT, namely, 10 % DMSO and 10 % GLY. The skin viability test confirmed that the skin protective capacity of 10 % DMSO and 10 % GLY was almost equal. The results of skin viability and IVPT showed that the skin viability and permeability of rat skin in 10 %DMSO or 10 % GLY were maintained for at least 7 and 30 days at -20 °C and -80 °C compared to fresh skin, respectively; in contrast, those of porcine skin were just maintained for <7 days at -20 °C and -80 °C. These results indicated that ex vivo skin for IVPT preserved at -80 °C in 10 % DMSO or 10 % GLY was optimal. Furthermore, skin permeability was independent of skin barrier integrity. Our study provides reference conditions for preserving IVPT skin, and skin viability can be a potential indicator of IVPT skin.

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RESUMEN

Nanocrystals (NCs) have the potential to enhance the oral bioavailability of Class IV drugs in the Biopharmaceutical Classification System (BCS) due to the absorption of the intact crystals. The performance is compromised by the dissolution of NCs. Drug NCs have recently been adopted as solid emulsifiers to prepare nanocrystal self-stabilized Pickering emulsions (NCSSPEs). They are advantageous in high drug loading and low side effects due to the specific drug loading mode and the absence of chemical surfactants. More importantly, NCSSPEs may further enhance the oral bioavailability of drug NCs by impeding their dissolution. This is especially true for BCS IV drugs. In this study, curcumin (CUR), a typical BCS IV drug, was adopted to prepare CUR-NCs stabilized Pickering emulsions using either indigestible (isopropyl palmitate, IPP) or digestible (soybean oil, SO) oils, i.e., IPP-PEs and SO-PEs. The optimized formulations were spheric with CUR-NCs adsorbed on the water/oil interface. The CUR concentration in the formulation reached 20 mg/mL, which was far beyond the solubility of CUR in IPP (158.06 ± 3.44 µg/g) or SO (124.19 ± 2.40 µg/g). Moreover, the Pickering emulsions enhanced the oral bioavailability of CUR-NCs, being 172.85% for IPP-PEs and 152.07% for SO-PEs. The digestibility of the oil phase affected the amounts of CUR-NCs that remained intact in lipolysis and, thus, the oral bioavailability. In conclusion, converting NCs into Pickering emulsions provides a novel strategy to enhance the oral bioavailability of CUR and BCS IV drugs.

RESUMEN

Biofilms are colonies of microorganisms that are embedded in autocrine extracellular polymeric substances (EPS), imparting antibiotic resistance and recalcitrant bacterial infection. Nanoparticles (NPs) can enhance the biofilm inhibition and eradication of delivered antibiotics. This is mainly because of enhanced EPS penetration and a high local drug concentration. As we discuss here, novel strategies are being developed to further enhance the antibiofilm capacity of NPs, including size optimization, surface modification, stimuli-triggered release, and combined strategies. Thus, NPs represent an effective and promising approach to combat biofilms.

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RESUMEN

Oxybutynin (OXY) is the most common drug to treat overactive bladder (OAB) syndrome. Transdermal administration is a more ideal route replacing oral administration to resolve problems of low bioavailability and severe side effects. However, commercial transdermal products of OXY frequently cause skin irritation and low permeation efficiency arising discontinued medication. Here, oxybutynin nanosuspension (OXY-NS) and its gel preparation (OXY-NG) were constructed to resolve these issues. In vitro permeation test and in vivo pharmacokinetics study confirmed that OXY-NG significantly enhanced the transdermal permeation of OXY, about 4-fold and 3-fold higher than oxybutynin coarse suspension (OXY-CG), respectively, and in vitro retention test certified that OXY-NG increased OXY concentration especially in viable epidermis (VE) and Dermis (about 3 times that of OXY-CG), consequently improving the bioavailability. Skin irritation assay demonstrated that OXY-NG would not trigger skin adverse effects. In addition, selectively blocking hair follicles test evidenced that hair follicles pathway played an important role in OXY-NS transdermal delivery. In general, by virtue of excellent drug loading, low toxicity and ease of scale-up, OXY-NG is a promising strategy to ameliorate skin permeation of insoluble OXY for better transdermal treatment for OAB, hence increasing its bioavailability, reducing adverse effects, and achieving good patient compliance.

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