Recent advances in lipid-based long-acting injectable depot formulations

Sharma, Reena; Yadav, Sheetal; Yadav, Vivek R.; Akhtar, Junia; Katari, Oly; Kuche, Kaushik; Jain, Sanyog

doi:10.1016/j.addr.2023.114901

Cited by 19 publications

(5 citation statements)

References 200 publications

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“…Subsequently, the release of drugs from these systems decreases over time, resulting in a sustained release pro le. The responsible for this release manner is the lipid phase incorporating the drug during the formation of NE (31,32). Our ndings align with the previous studies by Yang et al (33) and Sari et al (34).…”

Section: Discussionsupporting

confidence: 92%

Preparation and evaluation of curcumin nanoemulsion to inhibit TC-1 cell growth

Karimi,

Qomi,

Jahromy

et al. 2024

Preprint

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Curcumin (Cur), a substance originating from Curcuma longa, has been comprehensively examined for its anticancer properties. Nonetheless, its clinical application has been restricted by its inadequate solubility, bioavailability, and stability. TC-1 cells have been impressive in understanding HPV biology and developing therapeutic approaches for HPV infection and related cancers, like cervical cancer, offering a close mimicry of HPV-induced carcinogenesis. This study's primary goal is to formulate and optimize curcumin nanoemulsions (Cur-NE) to address these challenges and, secondarily, evaluate their impact on TC-1 cell growth. Characterization of the nanoemulsions was conducted using dynamic light scattering (DLS), transmission electron microscopy (TEM) and High-performance liquid chromatography (HPLC) revealing an average particle size of 52.5 nm, a zeta potential of -13.1 mV, and a drug content of 94.6%. Through the dialysis diffusion technique, drug release profiles demonstrated a sustained, slower release of Cur from Cur-NE compared to free curcumin. According to an MTT assay, Cur-Ne with an IC50 35 µg/ml exhibited an increased inhibitory effect of Cur on TC-1 cancer cells, while showing no inhibitory effects on MC3T3 normal cells at concentrations up to 100 µg/ml. In summary, this study underscores the potential of nanoemulsions as efficient carriers for Cur, with demonstrated safety in both cancer and normal cells. Moreover, Cur-NE displayed substantial inhibitory activity against TC-1 cancer cells, suggesting its promise in treating HPV-associated cancers, particularly cervical cancer. Further research is warranted to evaluate the long-term safety of this nanoemulsion for clinical trials and its efficacy against other cancer cell lines.

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Section: Discussionsupporting

confidence: 92%

Preparation and evaluation of curcumin nanoemulsion to inhibit TC-1 cell growth

Karimi,

Qomi,

Jahromy

et al. 2024

Preprint

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“…"Sustained release drug carriers" are designed to gradually release pharmaceuticals into the bloodstream, thereby reducing blood concentrations of medication over time. 55,56 This approach addresses the limitations or problems associated with standard medication therapy, F I G U R E 5 Problems associated with the treatment of HIV infection with daily dosing injection. HIV, human immunodeficiency virus.…”

Section: Injectable Formulations For Sustained Drug Releasementioning

confidence: 99%

Human immunodeficiency virus infection challenges: Current therapeutic limitations and strategies for improved management through long‐acting injectable formulation

Tanushree,

Sharma,

Monika

et al. 2024

Reviews in Medical Virology

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HIV infection has been a severe global health burden, with millions living with the virus and continuing new infections each year. Antiretroviral therapy can effectively suppress HIV replication but requires strict lifelong adherence to daily oral medication regimens, which presents a significant challenge. Long‐acting formulations of antiretroviral drugs administered infrequently have emerged as a promising strategy to improve treatment outcomes and adherence to HIV therapy and prevention. Long‐acting injectable (LAI) formulations are designed to gradually release drugs over extended periods of weeks or months following a single injection. Critical advantages of LAIs over conventional oral dosage forms include less frequent dosing requirements, enhanced patient privacy, reduced stigma associated with daily pill regimens, and optimised pharmacokinetic/pharmacodynamic profiles. Several LAI antiretroviral products have recently gained regulatory approval, such as the integrase strand transfer inhibitor cabotegravir for HIV preexposure prophylaxis and the Cabotegravir/Rilpivirine combination for HIV treatment. A leading approach for developing long‐acting antiretroviral depots involves encapsulating drug compounds in polymeric microspheres composed of biocompatible, biodegradable materials like poly (lactic‐co‐glycolic acid). These injectable depot formulations enable high drug loading with customisable extended‐release kinetics controlled by the polymeric matrix. Compared to daily oral therapies, LAI antiretroviral formulations leveraging biodegradable polymeric microspheres offer notable benefits, including prolonged therapeutic effects, reduced dosing frequency for improved adherence, and the potential to kerb the initial HIV transmission event. The present manuscript aims to review the pathogenesis of the virus and its progression and propose therapeutic targets and long‐acting drug delivery strategies that hold substantial promise for enhancing outcomes in HIV treatment and prevention.

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“… 1 , 2 Several pharmaceutical approaches have been explored in designing injectable LA systems of chemicals, including polymeric microparticles, liposomes, in situ gelling/implant systems, and drug crystalline suspensions. 3 , 4 , 5 , 6 , 7 Injectable drug suspensions generally consist of nano‐ or micrometer sized (pro)drug particles suspended in aqueous vehicles with minimal use of steric or electrostatic stabilizers (surfactants or hydrophilic polymers). 8 , 9 This carrier‐free LA system allows high drug‐loading, effective particle size control, and long‐term stability with well‐established fabrication process, leading to its successful commercialization including DepoMedrol® (methylprednisolone acetate), Depo‐Provera® (medroxyprogesterone acetate), Kenalog® (triamcinolone acetonide), Invega Sustenna® (paliperidone palmitate), Abilify Maintena® (aripiprazole), Aristada® (Aripiprazole Lauroxil), and Cabenuva® (cabotegravir and rilpivirine).…”

Section: Introductionmentioning

confidence: 99%

Tricaprylin‐based drug crystalline suspension for intramuscular long‐acting delivery of entecavir with alleviated local inflammation

Jeong,

Ho,

Park

et al. 2024

Bioengineering & Transla Med

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In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin‐based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3‐palmitate (EV‐P), an ester lipidic prodrug for entecavir (EV), was employed. The EV‐P‐loaded TS was prepared by ultra‐sonication method. Prepared TS and conventional AS exhibited comparable morphology (rod or rectangular), median diameter (2.7 and 2.6 μm), crystallinity (melting point of 160–165°C), and in vitro dissolution profile. However, in vivo performances of drug microparticles were markedly different, depending on delivery vehicle. At AS‐injected site, drug aggregates of up to 500 μm were formed upon intramuscular injection, and were surrounded with inflammatory cells and fibroblastic bands. In contrast, no distinct particle aggregation and adjacent granulation was observed at TS‐injected site, with >4 weeks remaining of the oily vehicle in micro‐computed tomographic observation. Surprisingly, TS exhibited markedly alleviated local inflammation compared to AS, endowing markedly lessened necrosis, fibrosis thickness, inflammatory area, and macrophage infiltration. The higher initial systemic exposure was observed with TS compared to AS, but TS provided prolonged delivery of EV for 3 weeks. Therefore, we suggest that the novel TS system can be a promising tool in designing parenteral long‐acting delivery, with improved local tolerability.

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Recent advances in lipid-based long-acting injectable depot formulations

Cited by 19 publications

References 200 publications

Preparation and evaluation of curcumin nanoemulsion to inhibit TC-1 cell growth

Preparation and evaluation of curcumin nanoemulsion to inhibit TC-1 cell growth

Human immunodeficiency virus infection challenges: Current therapeutic limitations and strategies for improved management through long‐acting injectable formulation

Tricaprylin‐based drug crystalline suspension for intramuscular long‐acting delivery of entecavir with alleviated local inflammation

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