To adequately reduce new HIV infections, development of highly effective pre-exposure prophylaxis (PrEP) against HIV infection in women is necessary. Cellulose acetate phthalate (CAP) is a pH sensitive polymer with HIV-1 entry inhibitory properties. Dolutegravir (DTG) is an integrase strand transfer inhibitor with potent antiretroviral activity. DTG delivered in combination with CAP may significantly improve current PrEP against HIV. In the present study the development of DTG-loaded CAP nanoparticles incorporated in thermosensitive (TMS) gel at vaginal pH 4.2 and seminal fluid pH 7.4 is presented as proof-of-concept for improved PrEP. Water–oil–in–water homogenization was used to fabricate DTG-loaded CAP nanoparticles (DTG–CAP–NPs). Size, polydispersity, and morphological analyses illustrate that DTG–CAP–NPs were smooth and spherical, ≤200 nm in size, and monodispersed with a polydispersity index PDI ≤ 0.2. The drug encapsulation (EE%) and release profile of DTG–CAP–NPs was determined by HPLC analysis. The EE% of DTG in DTG–CAP–NPs was evaluated to be ∼70%. The thermal sensitivity of the TMS gel was optimized and the pH dependency was evaluated by rheological analysis. DTG release studies in TMS gel revealed that DTG–CAP–NPs were stable in TMS gel at pH 4.2 while DTG–CAP–NPs in TMS gel at pH 7.4 rapidly release DTG (≥80% release within 1 h). Cytotoxicity studies using vaginal cell lines revealed that DTG–CAP–NPs were relatively non-cytotoxic at concentration <1 μg/mL. Confocal microscopic studies illustrate that ≥98% cells retained DTG–CAP–NPs intracellularly over seven days. Antiretroviral drug loaded nanocellulose fabrications in TMS gel delivered intravaginally may enhance both microbicidal and antiretroviral drug efficacy and may present a novel option for female PrEP against HIV.

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Background. Right heart thrombus or clot in transit is a rare venous thromboembolism (VTE) with high mortality. COVID-19 infection has been associated with increased risk of such events. We present the case of a 63-year-old man with no traditional VTE risk factors who was diagnosed with a clot in transit three weeks after diagnosis of COVID-19. Clinical Case. A 63-year-old male with no significant past medical history who presented to the emergency department with shortness of breath. He tested positive for COVID-19 three weeks prior. His oxygen saturation was 60% on room air and was put on nonrebreather mask. He was still showing signs of respiratory distress including tachypnea, tachycardia, diaphoresis, and accessory muscle use. The patient was subsequently intubated and mechanically ventilated. Chest computed tomography with contrast showed acute bilateral pulmonary emboli with flattening of the interventricular septum suggestive of right heart strain. Bedside echocardiogram showed severely enlarged right ventricle with reduced systolic function and evidence of right ventricular strain and a mobile echodensity in the right ventricle attached to the tricuspid valve consistent with a clot in transit. The patient was treated with full dose systemic thrombolysis with rapid improvement in his symptoms. He was extubated the following day and a repeat echocardiogram showed resolution of the clot in transit. Conclusion. Clot in transit is rare but can occur in COVID-19 patients even in the absence of traditional thromboembolism risk factors. Management includes systemic anticoagulation, systemic thrombolysis, and surgical embolectomy. Our patient was successfully treated with systemic thrombolysis.