- Material of fabrication must be biodegrade in a timely manner and form biologically acceptable degradation products.
- Carrier must contain an effective dose of active agent.
- Carrier formulation must have acceptable shelf life stability.
- Rate of drug release from carrier must occur at an acceptable rate.
- Carrier system must not cause increased toxicity and must be sterile.
- Carrier system must be capable of being administered routinely and in a non-offensive manner.
- Particles must be capable of being produced reliably in amounts that fulfill demand.
- Carrier system must be cost effective.
Carrier must be manufactured from materials that are biocompatible Various particulate drug carrier systems have been used-
Incorporating drugs into biodegradable liposome formulation offers several benefits including protection from premature degradation, altered biodisposition and pharmacokinetics alleviating dose limiting toxicity improved solubility if the agent is amphipathic and simultaneous incorporation of multiple reverse compounds delivered to a common site.
Liposomes have been employed as site specific carriers since, on administration, they concentrate in the organs bearing fenostrated capillaries, such as liver, spleen, bone marrow and therefore, form ideal substrate carriers for antineoplastic drugs. Several liposomal formulations of drugs viz. doxorubicin, daunorubicin, 4 epimere of doxorubicin, epirubicin, annamycin, campthothericin, mitoxanrone, paclitaxel, interleukin -2 etc. have already been studied. The liposomal formulations of doxorubicin has been observed to improve the therapeutic index of the drug by changing the drug disposition leading to a decreased occurrence of doxorubicin related cardiac toxicity. Liposomal encapsulation of interleukin -2 decreased overall toxicity while maintaining immuno modulatory activity.
With the recent discovery of different stealth lipid formulations, liposomes may now avoid the RES for prolonged periods and remain in the circulation for many hours. However, it is unclear whether an increased residence time in the circulation will translate into a higher therapeutic index.
Several types of liposomes are now available :
a) Target sensitive immunoliposome: -
Target sensitive immunoliposomes are composed of a contact sensitive phospholipid formulation, engineered to deliver and release a variety of drugs at the outer cell surface following antibody specific binding of the liposome to the desired cell. The result is a transient high local concentration of drug at the targeted cell surface followed by rapid uptake into the cell.
The primary advantage of these liposomes is that the target cell need not engulf or process the liposomes intracellularly for drug release to occur.
b) pH Sensitive Liposomes :
pH sensitive immunoliposomes circumvent the typical lysosomal inactivation of liposome entrapped drugs, which has caused quite a low efficacy for drugs delivered by conventional liposomes. Acid-labile liposomes are able to release their entrapped contents directly into the cytoplasm of the target cell, presumably because of their inherent pH-dependent instability in the pre-lysosomal membrane compartments such as the endosomes. This type of immunoliposome can be employed to enhance transfection efficiency through its more effective mechanism of DNA injection directly into the cell cytoplasm. Thus, it also has the potential for highly efficient and targeted delivery of smaller nucleic acid assemblies, such as antisense DNA.
c) Multiple Vesicle Liposome :
Multiple Vesicle Liposomes is a liposome as vesicle-within-a vesicle called a vesosome. In this case, individual vesicles are programmed to release drugs at different times enabling low level sustained release or drugs for treating cancer, gangrene or wounds. Alternatively the vesicles could simultaneously release “toxic cocktail” of drugs at the site of a tumor.