Superhydrophobic surfaces are generally made by controlling the surface chemistry and surface roughness of various expensive materials, which are then applied by means of complex time-consuming processes. We describe a simple and inexpensive method for forming a superhydrophobic coating using polypropylene (a simple polymer) and a suitable selection of solvents and temperature to control the surface roughness. The resulting gel-like porous coating has a water contact angle of 160 degrees. The method can be applied to a variety of surfaces as long as the solvent mixture does not dissolve the underlying material.

His Ph.D. research involves the synthesis of dithienothiophene (DTT) and ethenedithiothiophene (EDTT) type compounds and their electrochemical polymerizations. His other research area includes controlled release of anticancer drugs in biodegradable polymers. Scheme 2. Thionation Mechanism of 3 and 4 Scheme 3. Formation of the Side Product 8 Scheme 4. Synthesis of 1,3,2-Dithiaphosphetane 2-Sulfides

Introduction 3419 2. Reactions of P 4 S 10 3421 2.1. Ketones 3421 2.2. Thionoesters, Dithioesters, Thionolactones, Dithiolactones, Thiolactones, and Dithiolethiones 3426 2.3. Amides and Lactams 3435 2.4. Imides 3448 2.5. Thiophenes 3451 2.6. Thiazolines, Thiazoles, and Thiazines 3454 2.7. Dithiazoles 3456 2.8. Thiadiazoles 3456 2.9. Imidazolines and Pyrimidines 3456 2.10. Alcohols 3458 2.11. PdO to PdS 3461 2.12. Reduction 3462 2.13. Nucleotides, Purines, and Pyrimidines 3463 2.14. Miscellaneous 3467 2.15. P 4 S 10 vs Lawesson's Reagent (LR) 3473 3. Conclusion 3473 4. Acknowledgments 3473 5. References 3473

No effective therapies currently exist for chronic rhinosinusitis (CRS), a persistent inflammatory condition characterized by the accumulation of highly viscoelastic mucus (CRSM) in the sinuses. Nanoparticle therapeutics offer promise for localized therapies for CRS, but must penetrate CRSM in order to avoid washout during sinus cleansing and to reach underlying epithelial cells. Prior research has not established whether nanoparticles can penetrate the tenacious CRSM barrier, or instead become trapped. Here, we first measured the diffusion rates of polystyrene nanoparticles and the same nanoparticles modified with muco-inert polyethylene glycol (PEG) coatings in fresh, minimally perturbed CRSM collected during endoscopic sinus surgery from CRS patients with and without nasal polyp. We found that uncoated polystyrene particles, previously shown to be mucoadhesive, were immobilized in all CRSM samples tested. In contrast, densely PEGylated particles as large as 200 nm were able to readily penetrate all CRSM samples from patients with CRS alone, and nearly half of CRSM samples from patients with nasal polyp. Based on the mobility of different sized PEGylated particles, we estimate the average pore size of fresh CRSM to be at least 150 ± 50 nm. Guided by these studies, we formulated mucus-penetrating particles (MPP) composed of PLGA and Pluronics, two materials with a long history of safety and use in humans. We showed that biodegradable MPP are capable of rapidly penetrating CRSM at average speeds up to only 20-fold slower than their theoretical speeds in water. Our findings strongly support the development of mucus-penetrating nanomedicines for the treatment of CRS.

No abstract

Local delivery of chemotherapeutics in the cervicovaginal tract using nanoparticles may reduce adverse side effects associated with systemic chemotherapy, while improving outcomes for early stage cervical cancer. We hypothesize drug-loaded nanoparticles must rapidly penetrate cervicovaginal mucus (CVM) lining the female reproductive tract to effectively deliver their payload to underlying diseased tissues in a uniform and sustained manner. We develop paclitaxel-loaded nanoparticles, composed entirely of polymers used in FDA-approved products, which rapidly penetrate human CVM and provide sustained drug release with minimal burst effect. We further employ a mouse model with aggressive cervical tumors established in the cervicovaginal tract to compare paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (conventional particles , or CP) and similar particles coated with Pluronic® F127 (mucus-penetrating particles , or MPP). CP are mucoadhesive and, thus, aggregated in mucus, while MPP achieve more uniform distribution and close proximity to cervical tumors. Paclitaxel-MPP suppress tumor growth more effectively and prolong median survival of mice compared to free paclitaxel or paclitaxel-CP. Histopathological studies demonstrate minimal toxicity to the cervicovaginal epithelia, suggesting paclitaxel-MPP may be safe for intravaginal use. These results demonstrate for the first time the in vivo advantages of polymer-based MPP for treatment of tumors localized to a mucosal surface.

Mucosal surfaces are protected by a highly viscoelastic and adhesive mucus layer that traps most foreign particles, including conventional drug and gene carriers. Trapped particles are eliminated on the order of seconds to hours by mucus clearance mechanisms, precluding sustained and targeted drug and nucleic acid delivery to mucosal tissues. We have previously shown that polymeric coatings that minimize adhesive interactions with mucus constituents lead to particles that rapidly penetrate human mucus secretions. Nevertheless, a particular challenge in formulating drug-loaded mucus penetrating particles (MPP) is that many commonly used surfactants are either mucoadhesive, or do not facilitate efficient drug encapsulation. We tested a novel surfactant molecule for particle formulation composed of Vitamin E conjugated to 5 kDa polyethylene glycol (VP5k). We show that VP5k-coated poly(lactide-co-glycolide) (PLGA) nanoparticles rapidly penetrate human cervicovaginal mucus, whereas PLGA nanoparticles coated with polyvinyl alcohol or Vitamin E conjugated to 1 kDa PEG were trapped. Importantly, VP5k facilitated high loading of paclitaxel, a frontline chemo drug, into PLGA MPP, with controlled release for at least 4 days and negligible burst release. Our results offer a promising new method for engineering biodegradable, drug-loaded MPP for sustained and targeted delivery of therapeutics at mucosal surfaces.

Mucus secretions coating entry points to the human body that are not covered by skin efficiently trap and clear conventional drug carriers, limiting controlled drug delivery at mucosal surfaces. To overcome this challenge, we recently engineered nanoparticles that readily penetrate a variety of human mucus secretions, which we termed mucus-penetrating particles (MPP). Here, we report a new biodegradable MPP formulation based on diblock copolymers of poly(lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA-PEG). PLGA-PEG nanoparticles prepared by a solvent diffusion method rapidly diffused through fresh, undiluted human cervicovaginal mucus (CVM) with an average speed only eightfold lower than their theoretical speed in water. In contrast, PLGA nanoparticles were slowed more than 12,000-fold in the same CVM secretions. Based on the measured diffusivities, as much as 75% of the PLGA-PEG nanoparticles are expected to penetrate a 10-μm-thick mucus layer within 30 min, whereas virtually no PLGA nanoparticles are expected to do so over the same duration. These results encourage further development of PLGA-PEG nanoparticles as mucus-penetrating drug carriers for improved drug and gene delivery to mucosal surfaces.