A new engineering process of biodegradable polymeric solid implants for ultra-long-acting drug delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Pharmaceutical Technology

Background:

• Long-acting injectable formulations are crucial for improving adherence in HIV prevention.
• Existing delivery systems face challenges in achieving high drug loading and sustained release profiles.
• Biodegradable polymeric solid implants offer a promising alternative for controlled drug delivery.

Purpose of the Study:

• To develop and characterize a novel long-acting biodegradable polymeric solid implant (PSI) for HIV prevention using dolutegravir (DTG).
• To evaluate the drug loading capacity, release kinetics, and stability of the developed PSI.
• To demonstrate the versatility of the fabrication process for tunable drug delivery.

Main Methods:

• Fabrication of PSIs using a three-step process: in-situ phase inversion, micronization, and compression.
• Incorporation of the integrase inhibitor dolutegravir (DTG) into poly(lactic-co-glycolic acid) (PLGA) implants.
• Assessment of drug loading, in-vitro release kinetics over 6 months, and physical/chemical stability under accelerated conditions.

Main Results:

• Achieved high drug loading capacity of up to 85 wt% DTG in the PSIs.
• Demonstrated sustained DTG release over 6 months with minimal burst release (<6% in 24h).
• Confirmed stability of DTG physical/chemical properties after 6 months of accelerated storage.

Conclusions:

• The novel PSI fabrication process enables high drug loading and sustained release of DTG for potential HIV prevention.
• Release kinetics can be precisely controlled by adjusting formulation parameters like drug concentration and polymer properties.
• This versatile technology presents a promising platform for long-acting injectable drug delivery, particularly for HIV prevention applications.